Same old

Cannabislike drugs may hold key to treating pain while bypassing the brain.

2008-11-13T00:53:00.001-08:00

Cannabislike drugs may hold key to treating pain while bypassing the brain.

JAMA. 2008 Nov 5;300(17):1987

Authors: Hampton T

PMID: 18984881 [PubMed - indexed for MEDLINE]

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No major role of common SV2A variation for predisposition or levetiracetam response in epilepsy.

2008-11-10T05:03:00.001-08:00

No major role of common SV2A variation for predisposition or levetiracetam response in epilepsy.

Epilepsy Res. 2008 Oct 30;

Authors: Lynch JM, Tate SK, Kinirons P, Weale ME, Cavalleri GL, Depondt C, Murphy K, O'Rourke D, Doherty CP, Shianna KV, Wood NW, Sander JW, Delanty N, Goldstein DB, Sisodiya SM

Levetiracetam (LEV), a newer antiepileptic drug (AED) useful for several epilepsy syndromes, binds to SV2A. Identifying genetic variants that influence response to LEV may allow more tailored use of LEV. Obvious candidate genes are SV2A, SV2B and SV2C, which encode the only known binding site, synaptic vesicle protein 2 (SV2), with LEV binding to the SV2A isoform. SV2A is an essential protein as homozygous SV2A knockout mice appear normal at birth but fail to grow, experience severe seizures and die by 3 weeks. We addressed characterising AED response issues in pharmacogenetics and whether variation in these genes associates with response to LEV in two independent cohorts with epilepsy. We also investigated whether variation in these three genes associated with epilepsy predisposition in two larger cohorts of patients with various epilepsy phenotypes. Common genetic variation in SV2A, encoding the actual binding site of LEV, was fully represented in this study whereas SV2B and SV2C were not fully covered. None of the polymorphisms tested in SV2A, SV2B or SV2C influence LEV response or predisposition to epilepsy. We found no association between genetic variation in SV2A, SV2B or SV2C and response to LEV or epilepsy predisposition. We suggest this study design may be used in future pharmacogenetic work examining AED or LEV efficacy. However, different study designs would be needed to examine common variation with minor effect sizes, or rare variation, influencing AED or LEV response or epilepsy predisposition.

PMID: 18977120 [PubMed - as supplied by publisher]

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Pro-drugs for indirect cannabinoids as therapeutic agents.

2008-11-10T05:02:00.001-08:00

Pro-drugs for indirect cannabinoids as therapeutic agents.

Curr Drug Deliv. 2008 Oct;5(4):243-7

Authors: Ashton J

Medicinal cannabis, cannabis extracts, and other cannabinoids are currently in use or under clinical trial investigation for the control of nausea, emesis and wasting in patients undergoing chemotherapy, the control of neuropathic pain and arthritic pain, and the control of the symptoms of multiple sclerosis. The further development of medicinal cannabinoids has been challenged with problems. These include the psychoactivity of cannabinoid CB1 receptor agonists and the lack of availability of highly selective cannabinoid receptor full agonists (for the CB1 or CB2 receptor), as well as problems of pharmacokinetics. Global activation of cannabinoid receptors is usually undesirable, and so enhancement of local endocannabinoid receptor activity with indirect cannabimimetics is an attractive strategy for therapeutic modulation of the endocannabinoid system. However, existing drugs of this type tend to be metabolized by the same enzymes as their target endocannabinoids and are not yet available in a form that is clinically useful. A potential solution to these problems may now have been suggested by the discovery that paracetamol (acetaminophen) exerts its analgesic (and probably anti-pyretic) effects by its degradation into an anandamide (an endocannabinoid) reuptake inhibitor (AM404) within the body, thus classifying it as pro-drug for an indirect cannabimimetic. Given the proven efficacy and safety of paracetamol, the challenge now is to develop related drugs, or entirely different substrates, into pro-drug indirect cannabimimetics with a similar safety profile to paracetamol but at high effective dose titrations.

PMID: 18855592 [PubMed - in process]

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Evaluation of interactions between cannabinoid compounds and diazepam in electroshock-induced seizure model in mice.

2008-11-10T04:59:00.001-08:00

Evaluation of interactions between cannabinoid compounds and diazepam in electroshock-induced seizure model in mice.

J Neural Transm. 2008 Jun 25;

Authors: Naderi N, Aziz Ahari F, Shafaghi B, Hosseini Najarkolaei A, Motamedi F

Several studies have shown that cannabinoids have anticonvulsant properties that are mediated through activation of the cannabinoid CB1 receptors. In addition, endogenous cannabinoid compounds (endocannabinoids) regulate synaptic transmission and dampen seizure activity via activation of the same receptors. The aim of this study was to evaluate the possible interactions between antiepileptic effects of cannabinoid compounds and diazepam using electroshock-induced model of seizure in mice. Electroconvulsions were produced by means of an alternating current (ear-clip electrodes, fixed current intensity 35 mA, stimulus duration 0.2 s) and tonic hindlimb extension was taken as the endpoint. All experiments were performed on groups of ten mice and the number of animals who did not display seizure reported as percent protection. Intraperitoneal (i.p.) administration of diazepam (0.25-2 mg/kg) and CB1 receptor agonist WIN55212-2 (0.5-4 mg/kg) dose dependently produced an antiepileptic effect evaluated in terms of increased percentage of protection against electroshock-induced seizure. Logistic regression analysis indicated synergistic interactions in anticonvulsant action after co-administration of diazepam and WIN55212-2 in fixed-ratio combination of 3:1 (diazepam:WIN55212-2), while an additive effect was resulted after co-administration of 1:1 and 1:3 fixed-ratio combinations. Administration of various doses of the endocannabinoid reuptake inhibitor, AM404, did not produce any effect on electroshock-induced seizure. Moreover, co-administration of AM404 and diazepam did not produce significant interaction in antiepileptic properties of these compounds. Administration of the fatty acid amide hydrolase inhibitor, URB597, produced significant antiepileptic effect. Co-administration of URB597 and diazepam led to an antagonistic interaction in protection against shock-induced seizure. Co-administration of different doses of the cannabinoid CB1 receptor antagonist, AM251 did not alter the antiepileptic effect of diazepam in the electroshock-induced seizure test. These results demonstrate that endocannabinoid system participates in the modulation of seizure and combination of small doses of exogenous CB1 receptor agonists with diazepam may have effective consequences in seizure control. Furthermore, inhibiting the endocannabinoid degradation could be more efficacious in modulating seizure than preventing their uptake. This study also suggests that the effects of cannabinoids on epilepsy depend on the relative cannabinoid responsiveness of GABAergic and glutamatergic neurotransmission. While, the antiepileptic effects of cannabinoid compounds are likely by affecting excitatory glutamate neurotransmission, the antagonistic interaction between cannabinoid compounds and diazepam to protect seizure is due to the cannabinoid action on inhibitory GABAergic system.

PMID: 18575801 [PubMed - as supplied by publisher]

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Elevation of pentylenetetrazole-induced seizure threshold in cholestatic mice: interaction between opioid and cannabinoid systems.

2008-11-10T04:58:00.001-08:00

Elevation of pentylenetetrazole-induced seizure threshold in cholestatic mice: interaction between opioid and cannabinoid systems.

J Gastroenterol Hepatol. 2008 Jul;23(7 Pt 2):e251-7

Authors: Shafaroodi H, Ghasemi M, Dehpour AR

BACKGROUND AND AIM: Several studies have reported that endogenous opioid and cannabinoid systems may be involved in some pathophysiological changes occurring in cholestatic liver disease. It is well known that endogenous opioids and cannabinoids alter the susceptibility of experimental animals to different models of seizure. METHODS: The alterations in pentylenetetrazole-induced clonic seizure thresholds were evaluated from 1 to 6 days after bile duct ligation in mice. Whether the pretreatment of cholestatic mice with different doses of opioid receptor antagonist naltrexone or cannabinoid CB(1) receptor antagonist AM251 (AM251) would have changed the clonic seizure threshold was also examined. RESULTS: Although the clonic seizure threshold was similar between sham-operated and unoperated mice, there was a time-dependent increase in the threshold in cholestatic mice, reaching a peak on day 3 after bile duct ligation and declining partially after day 4. Chronic pretreatment with naltrexone (2, 5, and 10 mg/kg) reversed the increased threshold in cholestatic mice on day 3 after operation in a dose-dependent manner with the highest doses used restoring the threshold to that of the control animals. A similar reversal of the increased threshold was observed after acute (0.5, 0.75, and 1 mg/kg) or chronic (0.5 mg/kg for 4 days) pretreatment with AM251. Moreover, concurrent administration of doses of AM251 and naltrexone that each separately induced a partial reversal of increased seizure threshold in cholestasis caused a complete restoring of the threshold to the control level. CONCLUSIONS: Both opioid and cannabinoid CB(1) receptors may be involved in the dramatic increase in pentylenetetrazole-induced seizure threshold in cholestasis.

PMID: 17764531 [PubMed - indexed for MEDLINE]

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Effects of levetiracetam on generalized discharges monitored with ambulatory EEG in epileptic patients.

2008-11-10T04:52:00.001-08:00

Effects of levetiracetam on generalized discharges monitored with ambulatory EEG in epileptic patients.

Seizure. 2008 Oct 1;

Authors: Pro S, Vicenzini E, Pulitano P, Voti PL, Zarabla A, Randi F, Mecarelli O

PURPOSE: Quantitative analysis of epileptiform discharges (EDs) before and after the initiation of an antiepileptic treatment is a useful tool to objectively documentate the efficacy of an antiepileptic drug (AED). Aim of this study was to evaluate the effect of levetiracetam (LEV) on EDs, monitored with ambulatory EEG (A/EEG), in a limited series of patients with generalized epilepsy. METHODS: We performed 24h A/EEG recording in basal condition and at follow-up after LEV therapy in 21 adult epileptic patients. Eleven received LEV as monotherapy and 10 as add-on. For each patient we quantified total epileptic activity considering the following parameters: total number, total duration, maximal duration and median duration of EDs. Self-reported information on the effect of LEV on clinical seizures was also collected, to determine the electro-clinical correlation. RESULTS: A high variability of the response to LEV was observed in the monotherapy group, without statistical differences for all the parameters investigated. A significant reduction of the total number of seizures (113.6 vs. 41.2; p=.01) was observed in patients in add-on therapy. The modifications of epileptiform EEG abnormalities did not necessarily correlate with the self-reported clinical impressions. DISCUSSION: The quantification of EDs monitored by A/EEG provides a useful objective support for evaluating the neurophysiologic profile and the real efficacy of an antiepileptic treatment. In our patients LEV was able to significantly reduce the EDs only in add-on therapy. Further larger studies are necessary to clarify the effects of LEV on electro-clinical features of generalized epilepsy.

PMID: 18835193 [PubMed - as supplied by publisher]

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Distribution of the olfactory fibre input into the olfactory tubercle of the in vitro isolated guinea pig brain.

2008-11-10T04:50:00.001-08:00

Distribution of the olfactory fibre input into the olfactory tubercle of the in vitro isolated guinea pig brain.

J Neurophysiol. 2008 Oct 15;

Authors: Carriero G, Uva L, Gnatkovsky V, de Curtis M

The olfactory tubercle (OT) is a cortical component of the olfactory system involved in reward mechanisms of drug abuse. This region covers an extensive part of the rostral ventral cerebrum and is relatively poorly investigated. The intrinsic network interactions evoked by olfactory input are here analysed in the OT of the in vitro isolated guinea pig brain by means of field potential analysis and optical imaging of voltage-sensitive signals. Stimulation of the lateral olfactory tract induces a monosynaptic response that progressively decreases in amplitude from lateral to medial. The monosynaptic input induces a disynaptic response that is proportionally larger in the medial portion of the OT. Direct stimulation of the piriform cortex and subsequent lesion of this pathway demonstrated the existence of a prominent associative projection from the anterior part of the piriform cortex to the lateral part of the OT. Optical and electrophysiological recordings of the signals evoked by stimulation of the olfactory tract during arterial perfusion with the voltage-sensitive dye di-2-ANEPEQ confirmed the pattern of distribution of the mono and disynaptic responses in the OT. Finally, current source density analysis of laminar profiles recorded with 16-channel silicon probes confirmed that the monosynaptic and disynaptic potentials localize in the most superficial and the deep portions of the plexiform layer I, as suggested by previous reports. This study sets the standard for further analysis of the modulation of network properties in this largely unexplored brain region.

PMID: 18922946 [PubMed - as supplied by publisher]

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Pavlov's moth: olfactory learning and spike timing-dependent plasticity.

2008-11-10T04:47:00.001-08:00

Pavlov's moth: olfactory learning and spike timing-dependent plasticity.

Nat Neurosci. 2008 Oct;11(10):1126-7

Authors: Meeks JP, Holy TE

PMID: 18818593 [PubMed - indexed for MEDLINE]

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Differential potentiation of early and late components evoked in olfactory cortex by stimulation of cortical association fibers.

2008-11-10T04:46:00.001-08:00

Differential potentiation of early and late components evoked in olfactory cortex by stimulation of cortical association fibers.

Brain Res. 2008 Oct 17;

Authors: Stripling JS, Galupo MP

The present study examined in detail the development and decay of potentiation induced in vivo by repeated high-frequency stimulation of cortical association fibers (AF) in piriform cortex (PC). Male Long-Evans rats with chronically-implanted stimulating and recording electrodes were administered potentiating AF stimulation (thirty 10-pulse 100-Hz trains) on 8 consecutive days, followed by a ninth administration after an 8-day layoff. The time course of potentiation was monitored by local field potentials evoked in the PC and olfactory bulb (OB) by 0.1 Hz single-pulse AF test stimulation before, during, and following each potentiating treatment. AF test stimulation evoked two distinct components in the PC, an early component (EC) and a late component (LC). High-frequency AF stimulation produced potentiation of each component, but with very different characteristics. EC potentiation consisted of a brief augmentation during each bout of potentiating stimulation that persisted <2 min after the last high-frequency train and showed no cumulative effects following repeated induction across days. In contrast, LC potentiation developed gradually, requiring several daily potentiation treatments to reach maximum amplitude, and decayed more slowly each time it was induced. Furthermore, LC potentiation persisted in latent form for at least 8 days following its apparent decay and could be reinstated by repeated test stimulation that was without effect at the beginning of the experiment. Potentiation in the OB resembled LC potentiation in its characteristics, but with less latent potentiation. These results indicate that the potentiation reported here is distinctly different from the long-term potentiation previously demonstrated in vitro in the PC, and suggest that this potentiation represents an increase in excitability within the cortical association fiber system that can be stored in latent form and retrieved at a later time. These characteristics make this potentiation a suitable candidate for participation in long-term functional changes within olfactory cortex.

PMID: 18955033 [PubMed - as supplied by publisher]

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Vote on Graphs « GraphJam: Music and Pop Culture in Charts and Graphs. Let us explain them.

2008-11-10T03:29:00.001-08:00

Vote on Graphs « GraphJam: Music and Pop Culture in Charts and Graphs. Let us explain them.

Why no c*nt and paste for the iPhone? • The Register

2008-11-05T04:34:00.001-08:00

Why no c*nt and paste for the iPhone? • The Register

Fukitol: The New Miracle Drug | Nick Lewis: The Blog

2008-10-16T09:36:00.001-07:00

Fukitol: The New Miracle Drug | Nick Lewis: The Blog

MDA7: a novel selective agonist for CB(2) receptor...[Br J Pharmacol. 2008] - PubMed Result

2008-10-13T06:06:00.001-07:00

MDA7: a novel selective agonist for CB(2) receptor...[Br J Pharmacol. 2008] - PubMed Result

Sad Guys on Trading Floors - Jazzhands will not save us now, my friend.

2008-10-10T08:07:00.001-07:00

Sad Guys on Trading Floors - Jazzhands will not save us now, my friend.

Sad Guys on Trading Floors - Ok, yeah, I’m holding down the reset button down....

2008-10-10T08:02:00.001-07:00

Sad Guys on Trading Floors - Ok, yeah, I’m holding down the reset button down....

Psychological and social sequelae of cannabis and ...[Lancet. 2004] - PubMed Result

2008-10-03T12:19:00.001-07:00

Psychological and social sequelae of cannabis and ...[Lancet. 2004] - PubMed Result

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2008-10-03T11:10:00.001-07:00

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The role of piriform cortex adenosine A1 receptors on hippocampal kindling.

2008-10-01T02:39:00.001-07:00

The role of piriform cortex adenosine A1 receptors on hippocampal kindling.

Can J Neurol Sci. 2008 May;35(2):226-31

Authors: Namvar S, Mirnajafi-Zadeh J, Fathollahi Y, Zeraati M

INTRODUCTION: The hippocampus and piriform cortex have a critical role in seizure propagation. In this study, the role of adenosine A1 receptors of piriform cortex on CA1 hippocampal kindled seizures was studied in rats. METHODS: Animals were implanted with a tripolar electrode in the right hippocampal CA1 region and two guide cannulae in the left and right piriform cortex. They were kindled by daily electrical stimulation of hippocampus. In fully kindled rats, N6- cyclohexyladenosine (CHA; a selective adenosine A1 receptors agonist) and 1,3-dimethyl-8-cyclopenthylxanthine (CPT a selective adenosine A1 receptor antagonist) were microinfused into the piriform cortex. The animals were stimulated at 5, 15 and 90 minutes (min) after drug injection. RESULTS: Obtained data showed that CHA (10 and 100 microM) reduced afterdischarge duration, stage 5 seizure duration, and total seizure duration at 5 and 15 min after drug injection. There was no significant change in latency to stage 4 seizure. CPT at concentration of 20 microM increased afterdischarge duration, stage 5 seizure duration, and total seizure duration and decreased latency to stage 4 seizure at 5 and 15 min post injection. Pretreatment of rats with CPT (10 microM), 5 min before CHA (100 microM), reduced the effect of CHA on seizure parameters. CONCLUSION: These results suggested that activity of adenosine A1 receptors in the piriform cortex has an anticonvulsant effect on kindled seizures resulting from electrical stimulation of the CA1 region of the hippocampus.

PMID: 18574939 [PubMed - in process]

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Age- and region-dependent patterns of Ca(2+) accumulations following status epilepticus.

2008-10-01T02:38:00.001-07:00

Age- and region-dependent patterns of Ca(2+) accumulations following status epilepticus.

Int J Dev Neurosci. 2008 Jul 17;

Authors: Friedman LK, Saghyan A, Peinado A, Keesey R

Elevated Ca(2+) concentrations have been implicated in cell death mechanisms following seizures, however, the age and brain region of intracellular Ca(2+) accumulations [Ca(2+)](i), may influence whether or not they are toxic. Therefore, we examined regional accumulations of (45)Ca(2+) by autoradiography from rats of several developmental stages (P14, P21, P30 and P60) at 5, 14, and 24h after status epilepticus. To determine whether the uptake was intracellular, Ca(2+) was also assessed in hippocampal slices with the dye indicator, Fura 2 AM at P14. Control animals accumulated low homogeneous levels of (45)Ca(2+); however, highly specific and age-dependent patterns of (45)Ca(2+) uptake were observed at 5h. (45)Ca(2+) accumulations were predominant in dorsal hippocampal regions, CA1/CA2/CA3a, in P14 and P21 rats and in CA3a and CA3c neurons of P30 and P60 rats. Selective midline and amygdala nuclei were marked at P14 but not at P21 and limbic accumulations recurred with maturation that were extensive at P30 and even more so at P60. At 14h, P14 and P21 rats had no persistent accumulations whereas P30 and P60 rats showed persistent uptake patterns within selective amygdala, thalamic and hypothalamic nuclei, and other limbic cortical regions that continued to differ at these ages. For example, piriform cortex accumulation was highest at P60. Fura 2AM imaging at P14 confirmed that Ca(2+) rises were intracellular and occurred in both vulnerable and invulnerable regions of the hippocampus, such as CA2 pyramidal and dentate granule cells. Silver impregnation showed predominant CA1 injury at P20 and P30 but CA3 injury at P60 whereas little or no injury was found in extrahippocampal structures at P14 and P20 but was modest at P30 and maximal at P60. Thus, at young ages there was an apparent dissociation between high (45)Ca(2+) accumulations and neurotoxicity whereas in adults a closer relationship was observed, particularly in the extrahippocampal structures.

PMID: 18687397 [PubMed - as supplied by publisher]

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GABAergic circuits control input-spike coupling in the piriform cortex.

2008-10-01T02:36:00.001-07:00

GABAergic circuits control input-spike coupling in the piriform cortex.

J Neurosci. 2008 Aug 27;28(35):8851-9

Authors: Luna VM, Schoppa NE

Odor coding in mammals is widely believed to involve synchronized gamma frequency (30-70 Hz) oscillations in the first processing structure, the olfactory bulb. How such inputs are read in downstream cortical structures however is not known. Here we used patch-clamp recordings in rat piriform cortex slices to examine cellular mechanisms that shape how the cortex integrates inputs from bulb mitral cells. Electrical stimulation of mitral cell axons in the lateral olfactory tract (LOT) resulted in excitation of pyramidal cells (PCs), which was followed approximately 10 ms later by inhibition that was highly reproducible between trials in its onset time. This inhibition was somatic in origin and appeared to be driven through a feedforward mechanism, wherein GABAergic interneurons were directly excited by mitral cell axons. The precise inhibition affected action potential firing in PCs in two distinct ways. First, by abruptly terminating PC excitation, it limited the PC response to each EPSP to exactly one, precisely timed action potential. In addition, inhibition limited the summation of EPSPs across time, such that PCs fired action potentials in strong preference for synchronized inputs arriving in a time window of <5 ms. Both mechanisms would help ensure that PCs respond faithfully and selectively to mitral cell inputs arriving as a synchronized gamma frequency pattern.

PMID: 18753387 [PubMed - in process]

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Google Image Result for http://bp2.blogger.com/_Se19XAPwVi8/RnBpY4DNShI/AAAAAAAABPM/blIEFrJgP7k/s400/rimonabant.jpg

2008-08-06T02:59:00.001-07:00

Google Image Result for http://3.bp.blogspot.com/_Se19XAPwVi8/RnBpY4DNShI/AAAAAAAABPM/blIEFrJgP7k/s400/rimonabant.jpg

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Effects of Delta(9)-tetrahydrocannabivarin on [(35)S]GTPgammaS binding in mouse brain cerebellum and piriform cortex membranes.

2008-07-02T00:35:00.001-07:00

Effects of Delta(9)-tetrahydrocannabivarin on [(35)S]GTPgammaS binding in mouse brain cerebellum and piriform cortex membranes.

Br J Pharmacol. 2008 May 19;

Authors: Dennis I, Whalley BJ, Stephens GJ

Background and purpose:We have recently shown that the phytocannabinoid Delta(9)-tetrahydrocannabivarin (Delta(9)-THCV) and the CB(1) receptor antagonist AM251 increase inhibitory neurotransmission in mouse cerebellum and also exhibit anticonvulsant activity in a rat piriform cortical (PC) model of epilepsy. Possible mechanisms underlying cannabinoid actions in the CNS include CB(1) receptor antagonism (by displacing endocannabinergic tone) or inverse agonism at constitutively active CB(1) receptors. Here, we investigate the mode of cannabinoid action in [(35)S]GTPgammaS binding assays.Experimental approach:Effects of Delta(9)-THCV and AM251 were tested either alone or against WIN55,212-2-induced increases in [(35)S]GTPgammaS binding in mouse cerebellar and PC membranes. Effects on non-CB receptor expressing CHO-D(2) cell membranes were also investigated.Key results:Delta(9)-THCV and AM251 both acted as potent antagonists of WIN55,212-2-induced increases in [(35)S]GTPgammaS binding in cerebellar and PC membranes (Delta(9)-THCV: pA(2)=7.62 and 7.44 respectively; AM251: pA(2)=9.93 and 9.88 respectively). At micromolar concentrations, Delta(9)-THCV or AM251 alone caused significant decreases in [(35)S]GTPgammaS binding; Delta(9)-THCV caused larger decreases than AM251. When applied alone in CHO-D(2) membranes, Delta(9)-THCV and AM251 also caused concentration-related decreases in G protein activity.Conclusions and implications:Delta(9)-THCV and AM251 act as CB(1) receptors antagonists in the cerebellum and PC, with AM251 being more potent than Delta(9)-THCV in both brain regions. Individually, Delta(9)-THCV or AM251 exhibited similar potency at CB(1) receptors in the cerebellum and the PC. At micromolar concentrations, Delta(9)-THCV and AM251 caused a non-CB receptor-mediated depression of basal [(35)S]GTPgammaS binding.British Journal of Pharmacology advance online publication, 19 May 2008; doi:10.1038/bjp.2008.190.

PMID: 18493244 [PubMed - as supplied by publisher]

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NEUROBIOLOGY OF A SIMPLE MEMORY.

2008-07-02T00:33:00.001-07:00

NEUROBIOLOGY OF A SIMPLE MEMORY.

J Neurophysiol. 2008 May 7;

Authors: Wilson DA, Linster C

Habituation is one of the simplest forms of memory, yet its neurobiological mechanisms remain largely unknown in mammalian systems. This review summarizes recent multidisciplinary analyses of the neurobiology of mammalian odor habituation including in vitro and in vivo synaptic physiology, sensory physiology, behavioral pharmacology and computational modeling approaches. The findings reveal that a metabotropic glutamate receptor mediated depression of afferent synapses to the olfactory cortex is necessary and perhaps sufficient to account for cortical sensory adaptation and short-term behavioral habituation. Further, long-term habituation is an NMDA receptor dependent process within the olfactory bulb. Thus, there is both a pharmacological and anatomical distinction between short-term and long-term memory for habituation. The differential locus of change underlying short- and long-term memory lead to predictable differences in their behavioral characteristics, such as specificity.

PMID: 18463176 [PubMed - as supplied by publisher]

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Mapping seizure pathways in the temporal lobe.

2008-07-02T00:32:00.001-07:00

Mapping seizure pathways in the temporal lobe.

Epilepsia. 2008;49 Suppl 3:23-30

Authors: McIntyre DC, Gilby KL

Interest in temporal lobe seizure pathways has a long history based initially on the human condition of temporal lobe epilepsy (TLE). This interest in TLE has extended more recently into explorations of experimental models. In this review, the network structures in the temporal lobe that are recruited in animal models during various forms of limbic seizures and status epilepticus are described. Common to all of the various models is recruitment of the parahippocampal cortices, including the piriform, perirhinal, and entorhinal areas. This cortical involvement is seen in in vitro and in vivo electrophysiological recordings throughout the network, in trans-synaptic neuroplastic changes in associated network structures manifest at the molecular level, in network energy utilization visualized by 14C2-deoxyglucose uptake, and finally, in the behavioral consequences of network lesions. The conclusions of the animal models reviewed here are very similar to those described for the human condition presented recently in the 2006 Lennox lecture by Warren Blume, and addressed 53 years ago in the quadrennial meeting of the ILAE in 1953 by Henri Gastaut.

PMID: 18304253 [PubMed - in process]

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Chronic electroconvulsive stimulation but not chronic restraint stress modulates mRNA expression of voltage-dependent potassium channels Kv7.2 and Kv11.1 in the rat piriform cortex.

2008-07-02T00:31:00.003-07:00

Chronic electroconvulsive stimulation but not chronic restraint stress modulates mRNA expression of voltage-dependent potassium channels Kv7.2 and Kv11.1 in the rat piriform cortex.

Brain Res. 2007 Oct 5;

Authors: Hjæresen ML, Hageman I, Wortwein G, Plenge P, Jørgensen MB

The mechanisms by which stress and electroconvulsive therapy exert opposite effects on the course of major depression are not known. Potential candidates might include the voltage-dependent potassium channels. Potassium channels play an important role in maintaining the resting membrane potential and controlling neuronal excitability. To explore this hypothesis, we examined the effects of one or several electroconvulsive stimulations and chronic restraint stress (6 h/day for 21 days) on the expression of voltage-dependent potassium channel Kv7.2, Kv11.1, and Kv11.3 mRNA in the rat brain using in situ hybridization. Repeated, but not acute, electroconvulsive stimulation increased Kv7.2 and Kv11.1 mRNA levels in the piriform cortex. In contrast, restraint stress had no significant effect on mRNA expression of Kv7.2, Kv11.1, or Kv11.3 in any of the brain regions examined. Thus, it appears that the investigated voltage-dependent potassium channels are not modulated by restraint stress at the level of mRNA expression. However, our findings suggest that repeated electroconvulsive stimulation alter Kv7.2 and Kv11.1 function in the piriform cortex, a finding with potential relevance for the chain of neurobiological events underlying the clinical effects of ECT.

PMID: 18511019 [PubMed - as supplied by publisher]

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The role of piriform cortex adenosine A1 receptors on hippocampal kindling.

2008-07-02T00:31:00.001-07:00

The role of piriform cortex adenosine A1 receptors on hippocampal kindling.

Can J Neurol Sci. 2008 May;35(2):226-31

Authors: Namvar S, Mirnajafi-Zadeh J, Fathollahi Y, Zeraati M

PMID: 18574939 [PubMed - in process]

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Fedora: Re: Logitech Webcam(USB) New Errors Posted

2008-05-29T03:30:00.001-07:00

Re: Logitech Webcam(USB) New Errors PostedFrom: Murali Parth (muralinux48_at_yahoo.com)Date: 07/05/04# Next message: Wolfgang Gill: "Re: Logitech Webcam(USB) New Errors Posted" * Previous message: Jeff Allison: "Re: Correct driver for VIA KM400 onboard graphics with FC2." * Next in thread: Wolfgang Gill: "Re: Logitech Webcam(USB) New Errors Posted" * Reply: Wolfgang Gill: "Re: Logitech Webcam(USB) New Errors Posted" * Messages sorted by: [ date ] [ thread ] [ subject ] [ author ] Date: Sun, 4 Jul 2004 20:32:24 -0700 (PDT)To: Redhat Fedora Hello List !Sorry to bother you again, but with fresher errors.Idownloaded the driver for Logitech QUICKCAM EXPRESSfrom the site : http://qce-ga.sourceforge.net.Thenafter extracting I ran the script "quickcam.sh" andthe following are the messages I got.It seems that theproblem lies with detection of the device.When I doan ls -l /dev/video0 and it displays the major,minornos. as 81 & 0 and /dev/video as 81 & 1.I removed thefile hwconf and ran "kudzu".It detects the USBcontroller as "desc: "VIA Technologies|VT82xxxxx UHCIUSB 1.1 Controller" .Now the result of quickcam.shfollows :'Now everything should be well and the drivercompiled.Let's then try actually loading the fresh driver andtestingif it works.Press Ctrl+C to quit, Enter to continue --->To load the driver, I need to know the root password.=== Entering root mode === I will now try to enable the SysRq key.If your computer crashes, you can try pressing: Alt + SysRq + S: Emergency Sync (writeeverything on hard disk) Alt + SysRq + U: Unmount all harddisks Alt + SysRq + B: Reboot system immediatelyPress Ctrl+C to quit, Enter to continue --->Now I finally will try to load the module.If you're unlucky, your computer might crash rightnow!!!!Consider long if you really want to continue.Press Ctrl+C to quit, Enter to continue --->You decided to do it, here we go...=== Leaving root mode ===The driver detected the following supported cameras:[!] No cameras detected.Try unloading and reloading the driver manually with rmmod quickcam; insmod ./quickcam.ko debug=-1and then checking whether there are any messagesindicatingproblems with command dmesgWARNING: I'll try to continue anyway, but thisprobably will fail.Press Ctrl+C to quit, Enter to continue --->I will be using , if there are more cameras I'll nottest them.Press Ctrl+C to quit, Enter to continue --->Testing if is correct.ls: : No such file or directoryls: : No such file or directory./quickcam.sh: line 547: [: too many argumentsls: : No such file or directoryls: : No such file or directory[!] major number is .Usually it should be 81, so there are problems ahead.WARNING: I'll try to continue anyway, but thisprobably will fail.Press Ctrl+C to quit, Enter to continue ---> Right now driver is loaded and ready to run.If you like, you can quit now and start using thecamera -you have good chances that it works, if no problemswere detected.If you have X Window System running and xawtvinstalled,I can now run it automatically for you.You will then also have opportunity to install thedriver permanently.Press Ctrl+C to quit, Enter to continue --->Launching xawtv (press q on xawtv window to quitit)... xawtv -noscale -noxv -c ""This is xawtv-3.92, running on Linux/i686(2.6.5-1.358)v4l-conf: option requires an argument -- cusage: v4l-conf [ options ] options: -q quiet -d X11 Display [:0.0] -c video device [/dev/video0] -b displays color depth is bpp -s shift display by bytes -f query frame buffer device for info -a set framebuffer address to (in hex, root only, successfulautodetect will overwrite this address) -1 force v4l API -2 force v4l2 APIv4l-conf had some trouble, trying to continue anywayv4l2: open : No such file or directoryv4l2: open : No such file or directoryv4l: open : No such file or directoryno video grabber device available Well, did it work, did you get a picture?If you did, you might now want to install the driverpermanently. Just proceed to do that...Press Ctrl+C to quit, Enter to continue --->Just an extra warning: the driver (quickcam.ko) andthe utility (qcset) will be now copied into systemdirectories. If you have already other versions,they will be overwritten. Verify by giving rootpassword.=== Entering root mode ===/usr/bin/install -c -D -m 644 quickcam.ko/lib/modules/2.6.5-1.358/misc/quickcam.ko/usr/bin/install -c -D -m 755 qcset/usr/local/bin/qcset/sbin/depmod -a=== Leaving root mode ===Hopefully the driver is now installed and can beloadedwith command modprobe quickcamas root. You can put this command into some startupscript to do it always automatically at boot.The exact location depends on distribution, and thisscript is yet too dumb to do this automatically.Press Ctrl+C to quit, Enter to continue --->Goodbye... 'Then I did the following :[root@muralinux qc-usb-0.6.0]# modprobe quickcam[root@muralinux qc-usb-0.6.0]# lsmodModule Size Used byquickcam 59060 0ohci_hcd 14748 0uhci_hcd 23708 0tuner 15380 0bttv 129292 0video_buf 14468 1 bttvi2c_algo_bit 7304 1 bttvv4l2_common 4864 1 bttvbtcx_risc 3592 1 bttvi2c_core 16388 3tuner,bttv,i2c_algo_bitvideodev 6656 2 quickcam,bttv---------------------------------------------Could anyone help me to provide clue to unravellingthis problem ? Thanks.Murali__________________________________________________Do You Yahoo!?Tired of spam? Yahoo! Mail has the best spam protection aroundhttp://mail.yahoo.com-- fedora-list mailing listfedora-list@redhat.comTo unsubscribe: http://www.redhat.com/mailman/listinfo/fedora-list# Next message: Wolfgang Gill: "Re: Logitech Webcam(USB) New Errors Posted" * Previous message: Jeff Allison: "Re: Correct driver for VIA KM400 onboard graphics with FC2." * Next in thread: Wolfgang Gill: "Re: Logitech Webcam(USB) New Errors Posted" * Reply: Wolfgang Gill: "Re: Logitech Webcam(USB) New Errors Posted" * Messages sorted by: [ date ] [ thread ] [ subject ] [ author ] Relevant Pages * Re: [SLE] Missing 3D (was Compiz issues.) ... This is driver file location in above package ... post-uninstall script that will call tiny-nvidia-installer. ... Strange that it didn't offered to prepare existing kernel sources first. ... It can be that Smart did just what is programmed to do, install rpm, run ... (SuSE) * Re: vbs to configure printer to remote machine ... Description The printer driver is unknown. ... Win32 error code 1797 ... copy the files you want to install into this directory. ... Microsoft Windows Script Host Version 5.6 ... (microsoft.public.windowsxp.print_fax) * Re: Adding IP printer and install driver via script ... The driver has to be installed using the setup program from HP. ... an inf file in \Windows\inf you might be able to install it with the "Add ... I figured out how to creat the standard TCP/IP port but I'm ... > This is the error that I get when I run the script I created... ... (microsoft.public.windows.server.scripting) * Re: a script to add a new printer ... You install first the port and the driver, ... >> with the MS Windows 2003 Server Resource Kit from a script. ... (microsoft.public.scripting.wsh) * Re: apsfilter question/problem ... I don't have a fix to your apsfilter issue, but if you you are interested in another possible printing solution... ... that mentioned that driver, 10) PPA printer, so I chose that. ... the apsfilter setup script found it & didn't complain. ... Do I need to install another more complete version? ... (freebsd-questions) We are proud to have Web Hosting and Rack Housing from 9 Net Avenue Deutschland.(09)derkeiler.com * Security * UNIX * Linux * Coding * Usenet * Mailing-Lists * Newsgroups * About * Privacy * Search * ImprintPath: linux.derkeiler.com > Mailing-Lists > Fedora > 2004-07 Print as PDF RSS Feed

Fedora: Re: Logitech Webcam(USB) New Errors Posted

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Linux Kernel Documentation :: video4linux : CARDLIST.bttv

2008-05-22T00:56:00.001-07:00

About Kernel Documentation Linux Kernel Contact Linux Resources Linux BlogDocumentation / video4linux / CARDLIST.bttvBased on kernel version 2.6.25. Page generated on 2008-04-18 21:22 EST.1 0 -> *** UNKNOWN/GENERIC ***2 1 -> MIRO PCTV3 2 -> Hauppauge (bt848)4 3 -> STB, Gateway P/N 6000699 (bt848)5 4 -> Intel Create and Share PCI/ Smart Video Recorder III6 5 -> Diamond DTV20007 6 -> AVerMedia TVPhone8 7 -> MATRIX-Vision MV-Delta9 8 -> Lifeview FlyVideo II (Bt848) LR26 / MAXI TV Video PCI2 LR2610 9 -> IMS/IXmicro TurboTV11 10 -> Hauppauge (bt878) [0070:13eb,0070:3900,2636:10b4]12 11 -> MIRO PCTV pro13 12 -> ADS Technologies Channel Surfer TV (bt848)14 13 -> AVerMedia TVCapture 98 [1461:0002,1461:0004,1461:0300]15 14 -> Aimslab Video Highway Xtreme (VHX)16 15 -> Zoltrix TV-Max [a1a0:a0fc]17 16 -> Prolink Pixelview PlayTV (bt878)18 17 -> Leadtek WinView 60119 18 -> AVEC Intercapture20 19 -> Lifeview FlyVideo II EZ /FlyKit LR38 Bt848 (capture only)21 20 -> CEI Raffles Card22 21 -> Lifeview FlyVideo 98/ Lucky Star Image World ConferenceTV LR5023 22 -> Askey CPH050/ Phoebe Tv Master + FM [14ff:3002]24 23 -> Modular Technology MM201/MM202/MM205/MM210/MM215 PCTV, bt878 [14c7:0101]25 24 -> Askey CPH05X/06X (bt878) [many vendors] [144f:3002,144f:3005,144f:5000,14ff:3000]26 25 -> Terratec TerraTV+ Version 1.0 (Bt848)/ Terra TValue Version 1.0/ Vobis TV-Boostar27 26 -> Hauppauge WinCam newer (bt878)28 27 -> Lifeview FlyVideo 98/ MAXI TV Video PCI2 LR5029 28 -> Terratec TerraTV+ Version 1.1 (bt878) [153b:1127,1852:1852]30 29 -> Imagenation PXC200 [1295:200a]31 30 -> Lifeview FlyVideo 98 LR50 [1f7f:1850]32 31 -> Formac iProTV, Formac ProTV I (bt848)33 32 -> Intel Create and Share PCI/ Smart Video Recorder III34 33 -> Terratec TerraTValue Version Bt878 [153b:1117,153b:1118,153b:1119,153b:111a,153b:1134,153b:5018]35 34 -> Leadtek WinFast 2000/ WinFast 2000 XP [107d:6606,107d:6609,6606:217d,f6ff:fff6]36 35 -> Lifeview FlyVideo 98 LR50 / Chronos Video Shuttle II [1851:1850,1851:a050]37 36 -> Lifeview FlyVideo 98FM LR50 / Typhoon TView TV/FM Tuner [1852:1852]38 37 -> Prolink PixelView PlayTV pro39 38 -> Askey CPH06X TView99 [144f:3000,144f:a005,a04f:a0fc]40 39 -> Pinnacle PCTV Studio/Rave [11bd:0012,bd11:1200,bd11:ff00,11bd:ff12]41 40 -> STB TV PCI FM, Gateway P/N 6000704 (bt878), 3Dfx VoodooTV 100 [10b4:2636,10b4:2645,121a:3060]42 41 -> AVerMedia TVPhone 98 [1461:0001,1461:0003]43 42 -> ProVideo PV951 [aa0c:146c]44 43 -> Little OnAir TV45 44 -> Sigma TVII-FM46 45 -> MATRIX-Vision MV-Delta 247 46 -> Zoltrix Genie TV/FM [15b0:4000,15b0:400a,15b0:400d,15b0:4010,15b0:4016]48 47 -> Terratec TV/Radio+ [153b:1123]49 48 -> Askey CPH03x/ Dynalink Magic TView50 49 -> IODATA GV-BCTV3/PCI [10fc:4020]51 50 -> Prolink PV-BT878P+4E / PixelView PlayTV PAK / Lenco MXTV-9578 CP52 51 -> Eagle Wireless Capricorn2 (bt878A)53 52 -> Pinnacle PCTV Studio Pro54 53 -> Typhoon TView RDS + FM Stereo / KNC1 TV Station RDS55 54 -> Lifeview FlyVideo 2000 /FlyVideo A2/ Lifetec LT 9415 TV [LR90]56 55 -> Askey CPH031/ BESTBUY Easy TV57 56 -> Lifeview FlyVideo 98FM LR50 [a051:41a0]58 57 -> GrandTec 'Grand Video Capture' (Bt848) [4344:4142]59 58 -> Askey CPH060/ Phoebe TV Master Only (No FM)60 59 -> Askey CPH03x TV Capturer61 60 -> Modular Technology MM100PCTV62 61 -> AG Electronics GMV1 [15cb:0101]63 62 -> Askey CPH061/ BESTBUY Easy TV (bt878)64 63 -> ATI TV-Wonder [1002:0001]65 64 -> ATI TV-Wonder VE [1002:0003]66 65 -> Lifeview FlyVideo 2000S LR9067 66 -> Terratec TValueRadio [153b:1135,153b:ff3b]68 67 -> IODATA GV-BCTV4/PCI [10fc:4050]69 68 -> 3Dfx VoodooTV FM (Euro) [10b4:2637]70 69 -> Active Imaging AIMMS71 70 -> Prolink Pixelview PV-BT878P+ (Rev.4C,8E)72 71 -> Lifeview FlyVideo 98EZ (capture only) LR51 [1851:1851]73 72 -> Prolink Pixelview PV-BT878P+9B (PlayTV Pro rev.9B FM+NICAM) [1554:4011]74 73 -> Sensoray 311 [6000:0311]75 74 -> RemoteVision MX (RV605)76 75 -> Powercolor MTV878/ MTV878R/ MTV878F77 76 -> Canopus WinDVR PCI (COMPAQ Presario 3524JP, 5112JP) [0e11:0079]78 77 -> GrandTec Multi Capture Card (Bt878)79 78 -> Jetway TV/Capture JW-TV878-FBK, Kworld KW-TV878RF [0a01:17de]80 79 -> DSP Design TCVIDEO81 80 -> Hauppauge WinTV PVR [0070:4500]82 81 -> IODATA GV-BCTV5/PCI [10fc:4070,10fc:d018]83 82 -> Osprey 100/150 (878) [0070:ff00]84 83 -> Osprey 100/150 (848)85 84 -> Osprey 101 (848)86 85 -> Osprey 101/15187 86 -> Osprey 101/151 w/ svid88 87 -> Osprey 200/201/250/25189 88 -> Osprey 200/250 [0070:ff01]90 89 -> Osprey 210/220/23091 90 -> Osprey 500 [0070:ff02]92 91 -> Osprey 540 [0070:ff04]93 92 -> Osprey 2000 [0070:ff03]94 93 -> IDS Eagle95 94 -> Pinnacle PCTV Sat [11bd:001c]96 95 -> Formac ProTV II (bt878)97 96 -> MachTV98 97 -> Euresys Picolo99 98 -> ProVideo PV150 [aa00:1460,aa01:1461,aa02:1462,aa03:1463,aa04:1464,aa05:1465,aa06:1466,aa07:1467]100 99 -> AD-TVK503101 100 -> Hercules Smart TV Stereo102 101 -> Pace TV & Radio Card103 102 -> IVC-200 [0000:a155,0001:a155,0002:a155,0003:a155,0100:a155,0101:a155,0102:a155,0103:a155]104 103 -> Grand X-Guard / Trust 814PCI [0304:0102]105 104 -> Nebula Electronics DigiTV [0071:0101]106 105 -> ProVideo PV143 [aa00:1430,aa00:1431,aa00:1432,aa00:1433,aa03:1433]107 106 -> PHYTEC VD-009-X1 MiniDIN (bt878)108 107 -> PHYTEC VD-009-X1 Combi (bt878)109 108 -> PHYTEC VD-009 MiniDIN (bt878)110 109 -> PHYTEC VD-009 Combi (bt878)111 110 -> IVC-100 [ff00:a132]112 111 -> IVC-120G [ff00:a182,ff01:a182,ff02:a182,ff03:a182,ff04:a182,ff05:a182,ff06:a182,ff07:a182,ff08:a182,ff09:a182,ff0a:a182,ff0b:a182,ff0c:a182,ff0d:a182,ff0e:a182,ff0f:a182]113 112 -> pcHDTV HD-2000 TV [7063:2000]114 113 -> Twinhan DST + clones [11bd:0026,1822:0001,270f:fc00,1822:0026]115 114 -> Winfast VC100 [107d:6607]116 115 -> Teppro TEV-560/InterVision IV-560117 116 -> SIMUS GVC1100 [aa6a:82b2]118 117 -> NGS NGSTV+119 118 -> LMLBT4120 119 -> Tekram M205 PRO121 120 -> Conceptronic CONTVFMi122 121 -> Euresys Picolo Tetra [1805:0105,1805:0106,1805:0107,1805:0108]123 122 -> Spirit TV Tuner124 123 -> AVerMedia AVerTV DVB-T 771 [1461:0771]125 124 -> AverMedia AverTV DVB-T 761 [1461:0761]126 125 -> MATRIX Vision Sigma-SQ127 126 -> MATRIX Vision Sigma-SLC128 127 -> APAC Viewcomp 878(AMAX)129 128 -> DViCO FusionHDTV DVB-T Lite [18ac:db10,18ac:db11]130 129 -> V-Gear MyVCD131 130 -> Super TV Tuner132 131 -> Tibet Systems 'Progress DVR' CS16133 132 -> Kodicom 4400R (master)134 133 -> Kodicom 4400R (slave)135 134 -> Adlink RTV24136 135 -> DViCO FusionHDTV 5 Lite [18ac:d500]137 136 -> Acorp Y878F [9511:1540]138 137 -> Conceptronic CTVFMi v2139 138 -> Prolink Pixelview PV-BT878P+ (Rev.2E)140 139 -> Prolink PixelView PlayTV MPEG2 PV-M4900141 140 -> Osprey 440 [0070:ff07]142 141 -> Asound Skyeye PCTV143 142 -> Sabrent TV-FM (bttv version)144 143 -> Hauppauge ImpactVCB (bt878) [0070:13eb]145 144 -> MagicTV146 145 -> SSAI Security Video Interface [4149:5353]147 146 -> SSAI Ultrasound Video Interface [414a:5353]148 147 -> VoodooTV 200 (USA) [121a:3000]149 148 -> DViCO FusionHDTV 2 [dbc0:d200]150 149 -> Typhoon TV-Tuner PCI (50684)Hide Line Numbers * CARDLIST.ivtv * ibmcam.txt * CARDLIST.cx23885 * README.saa7134 * zr364xx.txt * w9968cf.txt * README.ir * README.cpia * et61x251.txt * CARDLIST.tuner * CARDLIST.usbvision * README.pvrusb2 * [ cx88 ] * CARDLIST.cx88 * Zoran * CQcam.txt * ov511.txt * extract_xc3028.pl * cpia2_overview.txt * radiotrack.txt * hauppauge-wintv-cx88-ir.txt * not-in-cx2388x-datasheet.txt * CARDLIST.saa7134 * cafe_ccic * [ video4linux ] * meye.txt * * API.html * CARDLIST.em28xx * README.cpia2 * sn9c102.txt * README.cx88 * stv680.txt * CARDLIST.bttv * [ cx2341x ] * v4lgrab.c * [ bttv ] * se401.txt * zc0301.txt * w9966.txt * lifeview.txt * README.ivtv * *About Kernel Documentation Linux Kernel Contact Linux Resources Linux BlogInformation is copyright its respective author. All material is available from the Linux Kernel Source distributed under a GPL License. This page is provided as a free service by mjmwired.net.

Linux Kernel Documentation :: video4linux : CARDLIST.bttv

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http://www.symons.net.au/16chan_dvr_card/dmesg-nforce3-gigabyte-k8ns-ultra-939-stable.txt

2008-05-22T00:55:00.001-07:00

Linux version 2.6.13-1.1526_FC4 (bhcompile@hs20-bc1-6.build.redhat.com) (gcc version 4.0.1 20050727 (Red Hat 4.0.1-5)) #1 Wed Sep 28 19:15:10 EDT 2005BIOS-provided physical RAM map: BIOS-e820: 0000000000000000 - 000000000009f800 (usable) BIOS-e820: 000000000009f800 - 00000000000a0000 (reserved) BIOS-e820: 00000000000f0000 - 0000000000100000 (reserved) BIOS-e820: 0000000000100000 - 000000001fff0000 (usable) BIOS-e820: 000000001fff0000 - 000000001fff3000 (ACPI NVS) BIOS-e820: 000000001fff3000 - 0000000020000000 (ACPI data) BIOS-e820: 00000000fec00000 - 00000000fec01000 (reserved) BIOS-e820: 00000000fee00000 - 00000000fee01000 (reserved) BIOS-e820: 00000000ffff0000 - 0000000100000000 (reserved)0MB HIGHMEM available.511MB LOWMEM available.Using x86 segment limits to approximate NX protectionOn node 0 totalpages: 131056 DMA zone: 4096 pages, LIFO batch:1 Normal zone: 126960 pages, LIFO batch:31 HighMem zone: 0 pages, LIFO batch:1DMI 2.3 present.ACPI: RSDP (v000 Nvidia ) @ 0x000f6d80ACPI: RSDT (v001 Nvidia AWRDACPI 0x42302e31 AWRD 0x01010101) @ 0x1fff3000ACPI: FADT (v001 Nvidia AWRDACPI 0x42302e31 AWRD 0x01010101) @ 0x1fff3040ACPI: MADT (v001 Nvidia AWRDACPI 0x42302e31 AWRD 0x01010101) @ 0x1fff79c0ACPI: DSDT (v001 NVIDIA AWRDACPI 0x00001000 MSFT 0x0100000c) @ 0x00000000ACPI: PM-Timer IO Port: 0x1008Allocating PCI resources starting at 20000000 (gap: 20000000:dec00000)Built 1 zonelistsKernel command line: ro root=LABEL=/ rhgbInitializing CPU#0CPU 0 irqstacks, hard=c04e7000 soft=c04e6000PID hash table entries: 2048 (order: 11, 32768 bytes)Detected 2100.225 MHz processor.Using pmtmr for high-res timesourceConsole: colour VGA+ 80x25Dentry cache hash table entries: 131072 (order: 7, 524288 bytes)Inode-cache hash table entries: 65536 (order: 6, 262144 bytes)Memory: 513264k/524224k available (3084k kernel code, 10364k reserved, 704k data, 176k init, 0k highmem)Checking if this processor honours the WP bit even in supervisor mode... Ok.Calibrating delay using timer specific routine.. 4204.70 BogoMIPS (lpj=8409404)Security Framework v1.0.0 initializedSELinux: Initializing.SELinux: Starting in permissive modeselinux_register_security: Registering secondary module capabilityCapability LSM initialized as secondaryMount-cache hash table entries: 512CPU: After generic identify, caps: 078bfbff e3d3fbff 00000000 00000000 00000001 00000000 00000001CPU: After vendor identify, caps: 078bfbff e3d3fbff 00000000 00000000 00000001 00000000 00000001CPU: L1 I Cache: 64K (64 bytes/line), D cache 64K (64 bytes/line)CPU: L2 Cache: 512K (64 bytes/line)CPU: After all inits, caps: 078bf3ff e3d3fbff 00000000 00000010 00000001 00000000 00000001Intel machine check architecture supported.Intel machine check reporting enabled on CPU#0.mtrr: v2.0 (20020519)CPU: AMD Athlon(tm) 64 Processor 3200+ stepping 00Enabling fast FPU save and restore... done.Enabling unmasked SIMD FPU exception support... done.Checking 'hlt' instruction... OK.ACPI: setting ELCR to 0200 (from 1e20)checking if image is initramfs... it isFreeing initrd memory: 1092k freedNET: Registered protocol family 16ACPI: bus type pci registeredPCI: PCI BIOS revision 2.10 entry at 0xfb560, last bus=3PCI: Using configuration type 1ACPI: Subsystem revision 20050408ACPI: Interpreter enabledACPI: Using PIC for interrupt routingACPI: PCI Root Bridge [PCI0] (0000:00)PCI: Probing PCI hardware (bus 00)ACPI: Assume root bridge [\_SB_.PCI0] segment is 0Boot video device is 0000:01:00.0ACPI: PCI Interrupt Routing Table [\_SB_.PCI0._PRT]ACPI: PCI Interrupt Routing Table [\_SB_.PCI0.HUB0._PRT]ACPI: Power Resource [ISAV] (on)ACPI: PCI Interrupt Routing Table [\_SB_.PCI0.AGPB._PRT]ACPI: PCI Interrupt Link [LNK1] (IRQs 3 4 5 6 7 9 10 *11 12 14 15)ACPI: PCI Interrupt Link [LNK2] (IRQs 3 4 5 6 7 9 *10 11 12 14 15)ACPI: PCI Interrupt Link [LNK3] (IRQs 3 4 5 6 7 9 *10 11 12 14 15)ACPI: PCI Interrupt Link [LNK4] (IRQs 3 4 *5 6 7 9 10 11 12 14 15)ACPI: PCI Interrupt Link [LNK5] (IRQs 3 4 5 6 7 *9 10 11 12 14 15)ACPI: PCI Interrupt Link [LUBA] (IRQs 3 4 *5 6 7 9 10 11 12 14 15)ACPI: PCI Interrupt Link [LUBB] (IRQs 3 4 *5 6 7 9 10 11 12 14 15)ACPI: PCI Interrupt Link [LMAC] (IRQs 3 4 5 6 7 9 10 11 *12 14 15)ACPI: PCI Interrupt Link [LAPU] (IRQs 3 4 5 6 7 9 10 11 12 14 15) *0, disabled.ACPI: PCI Interrupt Link [LACI] (IRQs 3 4 5 6 7 9 10 11 *12 14 15)ACPI: PCI Interrupt Link [LMCI] (IRQs 3 4 5 6 7 9 10 11 12 14 15) *0, disabled.ACPI: PCI Interrupt Link [LSMB] (IRQs 3 4 5 6 7 9 10 11 *12 14 15)ACPI: PCI Interrupt Link [LUB2] (IRQs 3 4 *5 6 7 9 10 11 12 14 15)ACPI: PCI Interrupt Link [LFIR] (IRQs 3 4 5 6 7 9 10 11 12 14 15) *0, disabled.ACPI: PCI Interrupt Link [L3CM] (IRQs 3 4 5 6 7 9 10 11 12 14 15) *0, disabled.ACPI: PCI Interrupt Link [LIDE] (IRQs 3 4 5 6 7 9 10 11 12 14 15) *0, disabled.ACPI: PCI Interrupt Link [LSID] (IRQs 3 4 5 6 7 9 10 11 12 14 15) *0, disabled.ACPI: PCI Interrupt Link [LFID] (IRQs 3 4 5 6 7 9 10 *11 12 14 15)ACPI: PCI Interrupt Link [APC1] (IRQs *16), disabled.ACPI: PCI Interrupt Link [APC2] (IRQs *17), disabled.ACPI: PCI Interrupt Link [APC3] (IRQs *18), disabled.ACPI: PCI Interrupt Link [APC4] (IRQs *19), disabled.ACPI: PCI Interrupt Link [APC5] (IRQs *16), disabled.ACPI: PCI Interrupt Link [APCF] (IRQs 20 21 22) *0, disabled.ACPI: PCI Interrupt Link [APCG] (IRQs 20 21 22) *0, disabled.ACPI: PCI Interrupt Link [APCH] (IRQs 20 21 22) *0, disabled.ACPI: PCI Interrupt Link [APCI] (IRQs 20 21 22) *0, disabled.ACPI: PCI Interrupt Link [APCJ] (IRQs 20 21 22) *0, disabled.ACPI: PCI Interrupt Link [APCK] (IRQs 20 21 22) *0, disabled.ACPI: PCI Interrupt Link [APCS] (IRQs *23), disabled.ACPI: PCI Interrupt Link [APCL] (IRQs 20 21 22) *0, disabled.ACPI: PCI Interrupt Link [APCM] (IRQs 20 21 22) *0, disabled.ACPI: PCI Interrupt Link [AP3C] (IRQs 20 21 22) *0, disabled.ACPI: PCI Interrupt Link [APCZ] (IRQs 20 21 22) *0, disabled.ACPI: PCI Interrupt Link [APSI] (IRQs 20 21 22) *0, disabled.ACPI: PCI Interrupt Link [APSJ] (IRQs 20 21 22) *0, disabled.Linux Plug and Play Support v0.97 (c) Adam Belaypnp: PnP ACPI initpnp: PnP ACPI: found 12 devicesusbcore: registered new driver usbfsusbcore: registered new driver hubPCI: Using ACPI for IRQ routingPCI: If a device doesn't work, try "pci=routeirq". If it helps, post a reportpnp: 00:00: ioport range 0x1000-0x107f could not be reservedpnp: 00:00: ioport range 0x1080-0x10ff has been reservedpnp: 00:00: ioport range 0x1400-0x147f has been reservedpnp: 00:00: ioport range 0x1480-0x14ff could not be reservedpnp: 00:00: ioport range 0x1800-0x187f has been reservedpnp: 00:00: ioport range 0x1880-0x18ff has been reservedPCI: Bridge: 0000:00:0b.0 IO window: disabled. MEM window: f2000000-f3ffffff PREFETCH window: f0000000-f1ffffffPCI: Bridge: 0000:02:06.0 IO window: disabled. MEM window: disabled. PREFETCH window: f6000000-f6ffffffPCI: Bridge: 0000:00:0e.0 IO window: 9000-afff MEM window: f4000000-f5ffffff PREFETCH window: f6000000-f7ffffffPCI: Setting latency timer of device 0000:00:0e.0 to 64apm: BIOS version 1.2 Flags 0x07 (Driver version 1.16ac)apm: overridden by ACPI.audit: initializing netlink socket (disabled)audit(1129167859.200:1): initializedTotal HugeTLB memory allocated, 0VFS: Disk quotas dquot_6.5.1Dquot-cache hash table entries: 1024 (order 0, 4096 bytes)SELinux: Registering netfilter hooksInitializing Cryptographic APIksign: Installing public key dataLoading keyring- Added public key 54AD4C348BA3456- User ID: Red Hat, Inc. (Kernel Module GPG key)pci_hotplug: PCI Hot Plug PCI Core version: 0.5ACPI: CPU0 (power states: C1[C1])isapnp: Scanning for PnP cards...isapnp: No Plug & Play device foundReal Time Clock Driver v1.12Linux agpgart interface v0.101 (c) Dave Jonesagpgart: Detected AGP bridge 0agpgart: Setting up Nforce3 AGP.agpgart: AGP aperture is 128M @ 0xe8000000PNP: PS/2 controller doesn't have AUX irq; using default 0xcPNP: PS/2 Controller [PNP0303:PS2K] at 0x60,0x64 irq 112serio: i8042 AUX port at 0x60,0x64 irq 12serio: i8042 KBD port at 0x60,0x64 irq 1Serial: 8250/16550 driver $Revision: 1.90 $ 32 ports, IRQ sharing enabledttyS0 at I/O 0x3f8 (irq = 4) is a 16550AttyS1 at I/O 0x2f8 (irq = 3) is a 16550AttyS0 at I/O 0x3f8 (irq = 4) is a 16550AttyS1 at I/O 0x2f8 (irq = 3) is a 16550Aio scheduler noop registeredio scheduler anticipatory registeredio scheduler deadline registeredio scheduler cfq registeredRAMDISK driver initialized: 16 RAM disks of 16384K size 1024 blocksizeUniform Multi-Platform E-IDE driver Revision: 7.00alpha2ide: Assuming 33MHz system bus speed for PIO modes; override with idebus=xxNFORCE3-250: IDE controller at PCI slot 0000:00:08.0NFORCE3-250: chipset revision 162NFORCE3-250: not 100% native mode: will probe irqs laterNFORCE3-250: BIOS didn't set cable bits correctly. Enabling workaround.NFORCE3-250: BIOS didn't set cable bits correctly. Enabling workaround.NFORCE3-250: 0000:00:08.0 (rev a2) UDMA133 controller ide0: BM-DMA at 0xf000-0xf007, BIOS settings: hda:DMA, hdb:DMA ide1: BM-DMA at 0xf008-0xf00f, BIOS settings: hdc:DMA, hdd:DMAProbing IDE interface ide0...hda: WDC WD2000JB-00GVC0, ATA DISK drivehdb: WDC WD2000JB-00GVA0, ATA DISK driveide0 at 0x1f0-0x1f7,0x3f6 on irq 14Probing IDE interface ide1...hdc: WDC WD800BB-75CAA0, ATA DISK driveide1 at 0x170-0x177,0x376 on irq 15hda: max request size: 1024KiBhda: 390721968 sectors (200049 MB) w/8192KiB Cache, CHS=24321/255/63, UDMA(100)hda: cache flushes supported hda: hda1 hda2 hda3 hda4hdb: max request size: 1024KiBhdb: 390721968 sectors (200049 MB) w/8192KiB Cache, CHS=24321/255/63, UDMA(100)hdb: cache flushes supported hdb: hdb1hdc: max request size: 128KiBhdc: Host Protected Area detected. current capacity is 156250000 sectors (80000 MB) native capacity is 156301488 sectors (80026 MB)hdc: Host Protected Area disabled.hdc: 156301488 sectors (80026 MB) w/2048KiB Cache, CHS=65535/16/63, UDMA(100)hdc: cache flushes not supported hdc: hdc1ide-floppy driver 0.99.newideusbcore: registered new driver hiddevusbcore: registered new driver usbhiddrivers/usb/input/hid-core.c: v2.01:USB HID core drivermice: PS/2 mouse device common for all micemd: md driver 0.90.2 MAX_MD_DEVS=256, MD_SB_DISKS=27md: bitmap version 3.38NET: Registered protocol family 2IP route cache hash table entries: 8192 (order: 3, 32768 bytes)TCP established hash table entries: 32768 (order: 6, 262144 bytes)TCP bind hash table entries: 32768 (order: 7, 917504 bytes)TCP: Hash tables configured (established 32768 bind 32768)TCP reno registeredTCP bic registeredInitializing IPsec netlink socketNET: Registered protocol family 1NET: Registered protocol family 17Using IPI Shortcut modeACPI wakeup devices: HUB0 HUB1 USB0 USB1 USB2 F139 MMAC MMCI UAR1 ACPI: (supports S0 S1 S4 S5)Freeing unused kernel memory: 176k freedkjournald starting. Commit interval 5 secondsEXT3-fs: mounted filesystem with ordered data mode.input: AT Translated Set 2 keyboard on isa0060/serio0SELinux: Disabled at runtime.SELinux: Unregistering netfilter hooksSCSI subsystem initializedlibata version 1.12 loaded.sata_nv version 0.6ACPI: PCI Interrupt Link [LFID] enabled at IRQ 11PCI: setting IRQ 11 as level-triggeredACPI: PCI Interrupt 0000:00:0a.0[A] -> Link [LFID] -> GSI 11 (level, low) -> IRQ 11PCI: Setting latency timer of device 0000:00:0a.0 to 64ata1: SATA max UDMA/133 cmd 0x9F0 ctl 0xBF2 bmdma 0xDC00 irq 11ata2: SATA max UDMA/133 cmd 0x970 ctl 0xB72 bmdma 0xDC08 irq 11ata1: no device found (phy stat 00000000)scsi0 : sata_nvata2: no device found (phy stat 00000000)scsi1 : sata_nvsata_sil version 0.9ACPI: PCI Interrupt Link [LNK2] enabled at IRQ 10PCI: setting IRQ 10 as level-triggeredACPI: PCI Interrupt 0000:02:0d.0[A] -> Link [LNK2] -> GSI 10 (level, low) -> IRQ 10ata3: SATA max UDMA/100 cmd 0xE0838080 ctl 0xE083808A bmdma 0xE0838000 irq 10ata4: SATA max UDMA/100 cmd 0xE08380C0 ctl 0xE08380CA bmdma 0xE0838008 irq 10ata3: no device found (phy stat 00000000)scsi2 : sata_silata4: no device found (phy stat 00000000)scsi3 : sata_silfloppy0: no floppy controllers foundACPI: PCI Interrupt Link [LNK4] enabled at IRQ 5PCI: setting IRQ 5 as level-triggeredACPI: PCI Interrupt 0000:02:0b.0[A] -> Link [LNK4] -> GSI 5 (level, low) -> IRQ 5ACPI: PCI Interrupt 0000:02:0b.0[A] -> Link [LNK4] -> GSI 5 (level, low) -> IRQ 5eth0: Yukon Gigabit Ethernet 10/100/1000Base-T Adapter PrefPort:A RlmtMode:Check Link StateACPI: PCI Interrupt Link [LACI] enabled at IRQ 12PCI: setting IRQ 12 as level-triggeredACPI: PCI Interrupt 0000:00:06.0[A] -> Link [LACI] -> GSI 12 (level, low) -> IRQ 12PCI: Setting latency timer of device 0000:00:06.0 to 64intel8x0_measure_ac97_clock: measured 54815 usecsintel8x0: clocking to 46984shpchp: shpc_init : shpc_cap_offset == 0shpchp: shpc_init : shpc_cap_offset == 0shpchp: shpc_init : shpc_cap_offset == 0shpchp: Standard Hot Plug PCI Controller Driver version: 0.4forcedeth.c: Reverse Engineered nForce ethernet driver. Version 0.35.ACPI: PCI Interrupt Link [LMAC] enabled at IRQ 12ACPI: PCI Interrupt 0000:00:05.0[A] -> Link [LMAC] -> GSI 12 (level, low) -> IRQ 12PCI: Setting latency timer of device 0000:00:05.0 to 64eth1: forcedeth.c: subsystem: 01458:e000 bound to 0000:00:05.0i2c_core: Unknown parameter `i2c_debug'i2c_adapter i2c-0: nForce2 SMBus adapter at 0x1c00i2c_adapter i2c-1: nForce2 SMBus adapter at 0x2000Linux video capture interface: v1.00bttv: driver version 0.9.16 loadedbttv: using 8 buffers with 2080k (520 pages) each for capturebttv: Bt8xx card found (0).ACPI: PCI Interrupt 0000:02:07.0[A] -> Link [LNK4] -> GSI 5 (level, low) -> IRQ 5bttv0: Bt878 (rev 17) at 0000:02:07.0, irq: 5, latency: 32, mmio: 0xf7000000bttv0: using: Prolink Pixelview PV-BT878P+ (Rev.4C,8E) [card=70,insmod option]bttv0: gpio: en=00000000, out=00000000 in=00f36000 [init]i2c-algo-bit.o: (0) scl=0, sda=0i2c-algo-bit.o: bt878 #0 [sw] seems to be busy.bttv0: using tuner=25tvaudio: TV audio decoder + audio/video mux drivertvaudio: known chips: tda9840,tda9873h,tda9874h/a,tda9850,tda9855,tea6300,tea6320,tea6420,tda8425,pic16c54 (PV951),ta8874zbttv0: registered device video0bttv0: registered device vbi0bttv0: PLL: 28636363 => 35468950 .. okbttv0: add subdevice "remote0"bttv: Bt8xx card found (1).ACPI: PCI Interrupt Link [LNK3] enabled at IRQ 10ACPI: PCI Interrupt 0000:03:0c.0[A] -> Link [LNK3] -> GSI 10 (level, low) -> IRQ 10bttv1: Bt878 (rev 17) at 0000:03:0c.0, irq: 10, latency: 32, mmio: 0xf6000000bttv1: using: Tibet Systems 'Progress DVR' CS16 [card=131,insmod option]bttv1: gpio: en=00000000, out=00000000 in=008fffff [init]i2c-algo-bit.o: (0) scl=1, sda=1i2c-algo-bit.o: (1) scl=1, sda=0i2c-algo-bit.o: (2) scl=1, sda=1i2c-algo-bit.o: (3) scl=0, sda=1i2c-algo-bit.o: (4) scl=1, sda=1i2c-algo-bit.o: bt878 #1 [sw] passed test.bttv1: using tuner=-1bttv1: i2c: checking for TDA9887 @ 0x86... not foundbttv1: registered device video1bttv1: registered device vbi1bttv1: PLL: 28636363 => 35468950 .. okbttv: Bt8xx card found (2).ACPI: PCI Interrupt 0000:03:0d.0[A] -> Link [LNK4] -> GSI 5 (level, low) -> IRQ 5bttv2: Bt878 (rev 17) at 0000:03:0d.0, irq: 5, latency: 32, mmio: 0xf6002000bttv2: using: Tibet Systems 'Progress DVR' CS16 [card=131,insmod option]bttv2: gpio: en=00000000, out=00000000 in=009fffff [init]i2c-algo-bit.o: (0) scl=1, sda=1i2c-algo-bit.o: (1) scl=1, sda=0i2c-algo-bit.o: (2) scl=1, sda=1i2c-algo-bit.o: (3) scl=0, sda=1i2c-algo-bit.o: (4) scl=1, sda=1i2c-algo-bit.o: bt878 #2 [sw] passed test.bttv2: using tuner=-1bttv2: i2c: checking for TDA9887 @ 0x86... not foundbttv2: registered device video2bttv2: registered device vbi2bttv2: PLL: 28636363 => 35468950 .. okbttv: Bt8xx card found (3).ACPI: PCI Interrupt Link [LNK1] enabled at IRQ 11ACPI: PCI Interrupt 0000:03:0e.0[A] -> Link [LNK1] -> GSI 11 (level, low) -> IRQ 11bttv3: Bt878 (rev 17) at 0000:03:0e.0, irq: 11, latency: 32, mmio: 0xf6004000bttv3: using: Tibet Systems 'Progress DVR' CS16 [card=131,insmod option]bttv3: gpio: en=00000000, out=00000000 in=00af7fff [init]i2c-algo-bit.o: (0) scl=1, sda=1i2c-algo-bit.o: (1) scl=1, sda=0i2c-algo-bit.o: (2) scl=1, sda=1i2c-algo-bit.o: (3) scl=0, sda=1i2c-algo-bit.o: (4) scl=1, sda=1i2c-algo-bit.o: bt878 #3 [sw] passed test.bttv3: using tuner=-1bttv3: i2c: checking for TDA9887 @ 0x86... not foundbttv3: registered device video3bttv3: registered device vbi3bttv3: PLL: 28636363 => 35468950 .. okbttv: Bt8xx card found (4).ACPI: PCI Interrupt 0000:03:0f.0[A] -> Link [LNK2] -> GSI 10 (level, low) -> IRQ 10bttv4: Bt878 (rev 17) at 0000:03:0f.0, irq: 10, latency: 32, mmio: 0xf6006000bttv4: using: Tibet Systems 'Progress DVR' CS16 [card=131,insmod option]bttv4: gpio: en=00000000, out=00000000 in=00bff5ff [init]i2c-algo-bit.o: (0) scl=1, sda=1i2c-algo-bit.o: (1) scl=1, sda=0i2c-algo-bit.o: (2) scl=1, sda=1i2c-algo-bit.o: (3) scl=0, sda=1i2c-algo-bit.o: (4) scl=1, sda=1i2c-algo-bit.o: bt878 #4 [sw] passed test.bttv4: using tuner=-1bttv4: i2c: checking for TDA9887 @ 0x86... not foundbttv4: registered device video4bttv4: registered device vbi4bttv4: PLL: 28636363 => 35468950 .. okbt878: AUDIO driver version 0.0.0 loadedbt878: Bt878 AUDIO function found (0).ACPI: PCI Interrupt 0000:02:07.1[A] -> Link [LNK4] -> GSI 5 (level, low) -> IRQ 5bt878(0): Bt878 (rev 17) at 02:07.1, irq: 5, latency: 32, memory: 0xf7001000bt878: Bt878 AUDIO function found (1).ACPI: PCI Interrupt 0000:03:0c.1[A] -> Link [LNK3] -> GSI 10 (level, low) -> IRQ 10bt878(1): Bt878 (rev 17) at 03:0c.1, irq: 10, latency: 32, memory: 0xf6001000bt878: Bt878 AUDIO function found (2).ACPI: PCI Interrupt 0000:03:0d.1[A] -> Link [LNK4] -> GSI 5 (level, low) -> IRQ 5bt878(2): Bt878 (rev 17) at 03:0d.1, irq: 5, latency: 32, memory: 0xf6003000bt878: Bt878 AUDIO function found (3).ACPI: PCI Interrupt 0000:03:0e.1[A] -> Link [LNK1] -> GSI 11 (level, low) -> IRQ 11bt878(3): Bt878 (rev 17) at 03:0e.1, irq: 11, latency: 32, memory: 0xf6005000bt878: Bt878 AUDIO function found (4).ACPI: PCI Interrupt 0000:03:0f.1[A] -> Link [LNK2] -> GSI 10 (level, low) -> IRQ 10bt878(4): Bt878 (rev 17) at 03:0f.1, irq: 10, latency: 32, memory: 0xf6007000ACPI: PCI Interrupt Link [LUB2] enabled at IRQ 5ACPI: PCI Interrupt 0000:00:02.2[C] -> Link [LUB2] -> GSI 5 (level, low) -> IRQ 5PCI: Setting latency timer of device 0000:00:02.2 to 64ehci_hcd 0000:00:02.2: EHCI Host Controllerehci_hcd 0000:00:02.2: debug port 1ehci_hcd 0000:00:02.2: new USB bus registered, assigned bus number 1ehci_hcd 0000:00:02.2: irq 5, io mem 0xf8004000PCI: cache line size of 64 is not supported by device 0000:00:02.2ehci_hcd 0000:00:02.2: USB 2.0 initialized, EHCI 1.00, driver 10 Dec 2004hub 1-0:1.0: USB hub foundhub 1-0:1.0: 8 ports detectedohci_hcd: 2005 April 22 USB 1.1 'Open' Host Controller (OHCI) Driver (PCI)ACPI: PCI Interrupt Link [LUBA] enabled at IRQ 5ACPI: PCI Interrupt 0000:00:02.0[A] -> Link [LUBA] -> GSI 5 (level, low) -> IRQ 5PCI: Setting latency timer of device 0000:00:02.0 to 64ohci_hcd 0000:00:02.0: OHCI Host Controllerohci_hcd 0000:00:02.0: new USB bus registered, assigned bus number 2ohci_hcd 0000:00:02.0: irq 5, io mem 0xf8002000hub 2-0:1.0: USB hub foundhub 2-0:1.0: 4 ports detectedACPI: PCI Interrupt Link [LUBB] enabled at IRQ 5ACPI: PCI Interrupt 0000:00:02.1[B] -> Link [LUBB] -> GSI 5 (level, low) -> IRQ 5PCI: Setting latency timer of device 0000:00:02.1 to 64ohci_hcd 0000:00:02.1: OHCI Host Controllerohci_hcd 0000:00:02.1: new USB bus registered, assigned bus number 3ohci_hcd 0000:00:02.1: irq 5, io mem 0xf8003000hub 3-0:1.0: USB hub foundhub 3-0:1.0: 4 ports detectedieee1394: Initialized config rom entry `ip1394'ohci1394: $Rev: 1299 $ Ben Collins ACPI: PCI Interrupt 0000:02:0e.0[A] -> Link [LNK3] -> GSI 10 (level, low) -> IRQ 10ohci1394: fw-host0: OHCI-1394 1.1 (PCI): IRQ=[10] MMIO=[f5008000-f50087ff] Max Packet=[4096]ieee1394: Host added: ID:BUS[0-00:1023] GUID[00148556000cd46a]ACPI: Power Button (FF) [PWRF]ACPI: Power Button (CM) [PWRB]ibm_acpi: ec object not foundmd: Autodetecting RAID arrays.md: autorun ...md: ... autorun DONE.device-mapper: 4.4.0-ioctl (2005-01-12) initialised: dm-devel@redhat.comEXT3 FS on hda3, internal journalkjournald starting. Commit interval 5 secondsEXT3 FS on hda1, internal journalEXT3-fs: mounted filesystem with ordered data mode.SGI XFS with ACLs, security attributes, large block numbers, no debug enabledSGI XFS Quota Management subsystemXFS mounting filesystem hdb1Ending clean XFS mount for filesystem: hdb1ReiserFS: hda4: found reiserfs format "3.6" with standard journalReiserFS: hda4: using ordered data modeReiserFS: hda4: journal params: device hda4, size 8192, journal first block 18, max trans len 1024, max batch 900, max commit age 30, max trans age 30ReiserFS: hda4: checking transaction log (hda4)ReiserFS: hda4: Using r5 hash to sort namesAdding 1004052k swap on /dev/hda2. Priority:-1 extents:1

http://www.symons.net.au/16chan_dvr_card/dmesg-nforce3-gigabyte-k8ns-ultra-939-stable.txt

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Modulation of CaV2.3 Calcium Channel Currents by Eugenol.

2008-04-16T17:44:00.001-07:00

Modulation of CaV2.3 Calcium Channel Currents by Eugenol.

J Dent Res. 2008 Feb;87(2):137-41

Authors: Chung G, Rhee JN, Jung SJ, Kim JS, Oh SB

Eugenol, a natural congener of capsaicin, is a routine analgesic agent in dentistry. We have recently demonstrated the inhibition of Ca(V)2.2 calcium channel and sodium channel currents to be molecular mechanisms underlying the analgesic effect of eugenol. We hypothesized that Ca(V)2.3 channels are also modulated by eugenol and investigated its mode of action using the whole-cell patch-clamp technique in a heterologous expression system. Eugenol inhibited calcium currents in the E52 cell line, stably expressing the human Ca(V)2.3 calcium channels, where TRPV1 is not endogenously expressed. The extent of current inhibition was not significantly different between naïve E52 cells and TRPV1-expressing E52 cells, suggesting no involvement of TRPV1. In contrast, TRPV1 activation is prerequisite for the inhibition of Ca(V)2.3 calcium channels by capsaicin. The results indicate that eugenol has mechanisms distinct from those of capsaicin for modulating Ca(V)2.3 channels. We suggest that inhibition of Ca(V)2.3 channels by eugenol might contribute to its analgesic effect.

PMID: 18218839 [PubMed - in process]

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The novel antiepileptic drug carisbamate (RWJ 333369) is effective in inhibiting spontaneous recurrent seizure discharges and blocking sustained repetitive firing in cultured hippocampal neurons.

2008-04-16T17:43:00.003-07:00

The novel antiepileptic drug carisbamate (RWJ 333369) is effective in inhibiting spontaneous recurrent seizure discharges and blocking sustained repetitive firing in cultured hippocampal neurons.

Epilepsy Res. 2008 Mar 17;

Authors: Deshpande LS, Nagarkatti N, Sombati S, Delorenzo RJ

This study was initiated to investigate effects of the novel neuromodulator carisbamate (RWJ 333369) in the hippocampal neuronal culture model of status epilepticus and spontaneous epileptiform discharges. Whole-cell current clamp techniques were used to determine the effects of carisbamate on spontaneous recurrent epileptiform discharges (SREDs, in vitro epilepsy), depolarization-induced sustained repetitive firing (SRF) and low Mg(2+)-induced continuous high frequency spiking (in vitro status epilepticus). This in vitro model is an important tool to study the effects of anticonvulsant drugs (AEDs) on SREDs that occur for the life of the neurons in culture. Carisbamate dose dependently blocked the expression and reoccurrence of SREDs. The ED(50) value for its antiepileptic effect was 58.75+/-2.43muM. Inhibition of SRF is considered a common attribute of many AEDs. Carisbamate (100muM) significantly decreased SRF in hippocampal neurons. All these effects of carisbamate were reversed during a 5 to 30min drug washout period. When exposed to low Mg(2+) medium cultured hippocampal neurons exhibit high frequency spiking. This form of in vitro status epilepticus is not effectively blocked by conventional AEDs that are known to be effective in treating status epilepticus in humans. Carisbamate, like phenytoin and phenobarbital, had little or no effect on low Mg(2+)-induced continuous high frequency spiking. These results characterize the effects of carisbamate in the hippocampal neuronal culture model of epileptiform discharges and suggest that the ability of carisbamate to inhibit depolarization-induced SRF may account in part for some of it's anticonvulsant effect.

PMID: 18353614 [PubMed - as supplied by publisher]

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Shaping Embodied Neural Networks for Adaptive Goal-directed Behavior.

2008-04-16T17:43:00.001-07:00

Shaping Embodied Neural Networks for Adaptive Goal-directed Behavior.

PLoS Comput Biol. 2008 Mar;4(3):e1000042

Authors: Chao ZC, Bakkum DJ, Potter SM

The acts of learning and memory are thought to emerge from the modifications of synaptic connections between neurons, as guided by sensory feedback during behavior. However, much is unknown about how such synaptic processes can sculpt and are sculpted by neuronal population dynamics and an interaction with the environment. Here, we embodied a simulated network, inspired by dissociated cortical neuronal cultures, with an artificial animal (an animat) through a sensory-motor loop consisting of structured stimuli, detailed activity metrics incorporating spatial information, and an adaptive training algorithm that takes advantage of spike timing dependent plasticity. By using our design, we demonstrated that the network was capable of learning associations between multiple sensory inputs and motor outputs, and the animat was able to adapt to a new sensory mapping to restore its goal behavior: move toward and stay within a user-defined area. We further showed that successful learning required proper selections of stimuli to encode sensory inputs and a variety of training stimuli with adaptive selection contingent on the animat's behavior. We also found that an individual network had the flexibility to achieve different multi-task goals, and the same goal behavior could be exhibited with different sets of network synaptic strengths. While lacking the characteristic layered structure of in vivo cortical tissue, the biologically inspired simulated networks could tune their activity in behaviorally relevant manners, demonstrating that leaky integrate-and-fire neural networks have an innate ability to process information. This closed-loop hybrid system is a useful tool to study the network properties intermediating synaptic plasticity and behavioral adaptation. The training algorithm provides a stepping stone towards designing future control systems, whether with artificial neural networks or biological animats themselves.

PMID: 18369432 [PubMed - in process]

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The phytocannabinoid Delta(9)-tetrahydrocannabivarin modulates inhibitory neurotransmission in the cerebellum.

2008-04-16T17:42:00.001-07:00

The phytocannabinoid Delta(9)-tetrahydrocannabivarin modulates inhibitory neurotransmission in the cerebellum.

Br J Pharmacol. 2008 Mar 3;

Authors: Ma YL, Weston SE, Whalley BJ, Stephens GJ

Background and purposeThe phytocannabinoid Delta(9)-tetrahydrocannabivarin (Delta(9)-THCV) has been reported to exhibit a diverse pharmacology; here, we investigate functional effects of Delta(9)-THCV, extracted from Cannabis sativa, using electrophysiological techniques to define its mechanism of action in the CNS.Experimental approachEffects of Delta(9)-THCV and synthetic cannabinoid agents on inhibitory neurotransmission at interneurone-Purkinje cell (IN-PC) synapses were correlated with effects on spontaneous PC output using single-cell and multi-electrode array (MEA) electrophysiological recordings respectively, in mouse cerebellar brain slices in vitro.Key resultsThe cannabinoid receptor agonist WIN 55,212-2 (WIN55) decreased miniature inhibitory postsynaptic current (mIPSC) frequency at IN-PC synapses. WIN55-induced inhibition was reversed by Delta(9)-THCV, and also by the CB(1) receptor antagonist AM251; Delta(9)-THCV or AM251 acted to increase mIPSC frequency beyond basal values. When applied alone, Delta(9)-THCV, AM251 or rimonabant increased mIPSC frequency. Pre-incubation with Delta(9)-THCV blocked WIN55-induced inhibition. In MEA recordings, WIN55 increased PC spike firing rate; Delta(9)-THCV and AM251 acted in the opposite direction to decrease spike firing. The effects of Delta(9)-THCV and WIN55 were attenuated by the GABA(A) receptor antagonist bicuculline methiodide.Conclusions and implicationsWe show for the first time that Delta(9)-THCV acts as a functional CB(1) receptor antagonist in the CNS to modulate inhibitory neurotransmission at IN-PC synapses and spontaneous PC output. Delta(9)-THCV- and AM251-induced increases in mIPSC frequency beyond basal levels were consistent with basal CB(1) receptor activity. WIN55-induced increases in PC spike firing rate were consistent with synaptic disinhibition; whilst Delta(9)-THCV- and AM251-induced decreases in spike firing suggest a mechanism of PC inhibition.British Journal of Pharmacology advance online publication, 3 March 2008; doi:10.1038/bjp.2008.57.

PMID: 18311186 [PubMed - as supplied by publisher]

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Reciprocal inhibition of G-protein signaling is induced by CB(1) cannabinoid and GABA(B) receptor interactions in rat hippocampal membranes.

2008-04-16T17:41:00.001-07:00

Reciprocal inhibition of G-protein signaling is induced by CB(1) cannabinoid and GABA(B) receptor interactions in rat hippocampal membranes.

Neurochem Int. 2008 Feb 29;

Authors: Cinar R, Freund TF, Katona I, Mackie K, Szucs M

Cannabinoid CB(1) and the metabotropic GABA(B) receptors have been shown to display similar pharmacological effects and co-localization in certain brain regions. Previous studies have reported a functional link between the two systems. As a first step to investigate the underlying molecular mechanism, here we show cross-inhibition of G-protein signaling between GABA(B) and CB(1) receptors in rat hippocampal membranes. The CB(1) agonist R-Win55,212-2 displayed high potency and efficacy in stimulating guanosine-5'-O-(3-[(35)S]thio)triphosphate, [(35)S]GTPgammaS binding. Its effect was completely blocked by the specific CB(1) antagonist AM251 suggesting that the signaling was via CB(1) receptors. The GABA(B) agonists baclofen and SKF97541 also elevated [(35)S]GTPgammaS binding by about 60%, with potency values in the micromolar range. Phaclofen behaved as a low potency antagonist with an ED(50) approximately 1mM. However, phaclofen at low doses (1 and 10nM) slightly but significantly attenuated maximal stimulation of [(35)S]GTPgammaS binding by the CB(1) agonist R-Win55,212-2. The observation that higher concentrations of phaclofen had no such effect rule out the possibility of its direct action on CB(1) receptors. The pharmacologically inactive stereoisomer S-Win55,212-3 had no effect either alone or in combination with phaclofen establishing that the interaction is stereospecific in hippocampus. The specific CB(1) antagonist AM251 at a low dose (1nM) also inhibited the efficacy of G-protein signaling of the GABA(B) receptor agonist SKF97541. Cross-talk of the two receptor systems was not detected in either spinal cord or cerebral cortex membranes. It is speculated that the interaction might occur via an allosteric interaction between a subset of GABA(B) and CB(1) receptors in rat hippocampal membranes. Although the exact molecular mechanism of the reciprocal inhibition between CB(1) and GABA(B) receptors will have to be explored by future studies it is intriguing that the cross-talk might be involved in balance tuning the endocannabinoid and GABAergic signaling in hippocampus.

PMID: 18407377 [PubMed - as supplied by publisher]

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Cannabinoids in health and disease.

2008-04-16T17:40:00.003-07:00

Cannabinoids in health and disease.

Dialogues Clin Neurosci. 2007;9(4):413-30

Authors: Kogan NM, Mechoulam R

Cannabis sativa L. preparations have been used in medicine for millenia. However, concern over the dangers of abuse led to the banning of the medicinal use of marijuana in most countries in the 1930s. Only recently, marijuana and individual natural and synthetic cannabinoid receptor agonists and antagonists, as well as chemically related compounds, whose mechanism of action is still obscure, have come back to being considered of therapeutic value. However, their use is highly restricted. Despite the mild addiction to cannabis and the possible enhancement of addiction to other substances of abuse, when combined with cannabis, the therapeutic value of cannabinoids is too high to be put aside. Numerous diseases, such as anorexia, emesis, pain, inflammation, multiple sclerosis, neurodegenerative disorders (Parkinson's disease, Huntington's disease, Tourette's syndrome, Alzheimer's disease), epilepsy, glaucoma, osteoporosis, schizophrenia, cardiovascular disorders, cancer, obesity, and metabolic syndrome-related disorders, to name just a few, are being treated or have the potential to be treated by cannabinoid agonists/antagonists/cannabinoid-related compounds. In view of the very low toxicity and the generally benign side effects of this group of compounds, neglecting or denying their clinical potential is unacceptable--instead, we need to work on the development of more selective cannabinoid receptor agonists/antagonists and related compounds, as well as on novel drugs of this family with better selectivity, distribution patterns, and pharmacokinetics, and--in cases where it is impossible to separate the desired clinical action and the psychoactivity--just to monitor these side effects carefully.

PMID: 18286801 [PubMed - in process]

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Levetiracetam Inhibits both ryanodine and IP3 receptor activated calcium induced calcium release in hippocampal neurons in culture.

2008-04-16T17:40:00.001-07:00

Levetiracetam Inhibits both ryanodine and IP3 receptor activated calcium induced calcium release in hippocampal neurons in culture.

Neurosci Lett. 2008 Mar 21;

Authors: Nagarkatti N, Deshpande LS, Delorenzo RJ

Epilepsy affects approximately 1% of the population worldwide, and there is a pressing need to develop new anti-epileptic drugs (AEDs) and understand their mechanisms of action. Levetiracetam (LEV) is a novel AED and despite its increasingly widespread clinical use, its mechanism of action is as yet undetermined. Intracellular calcium ([Ca(2+)](i)) regulation by both inositol 1,4,5-triphosphate receptors (IP3R) and ryanodine receptors (RyR) has been implicated in epileptogenesis and the maintenance of epilepsy. To this end, we investigated the effect of LEV on RyR and IP3R activated calcium-induced calcium release (CICR) in hippocampal neuronal cultures. RyR-mediated CICR was stimulated using the well-characterized RyR activator, caffeine. Caffeine (10mM) caused a significant increase in [Ca(2+)](i) in hippocampal neurons. Treatment with LEV (33muM) prior to stimulation of RyR-mediated CICR by caffeine led to a 61% decrease in the caffeine induced peak height of [Ca(2+)](i) when compared to the control. Bradykinin stimulates IP3R-activated CICR-to test the effect of LEV on IP3R-mediated CICR, bradykinin (1muM) was used to stimulate cells pre-treated with LEV (100muM). The data showed that LEV caused a 74% decrease in IP3R-mediated CICR compared to the control. In previous studies we have shown that altered Ca(2+) homeostatic mechanisms play a role in seizure activity and the development of spontaneous recurrent epileptiform discharges (SREDs). Elevations in [Ca(2+)](i) mediated by CICR systems have been associated with neurotoxicity, changes in neuronal plasticity, and the development of AE. Thus, the ability of LEV to modulate the two major CICR systems demonstrates an important molecular effect of this agent on a major second messenger system in neurons.

PMID: 18406528 [PubMed - as supplied by publisher]

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http://www.ncbi.nlm.nih.gov/pubmed/7494858?ordinalpos=79&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

2008-04-16T17:39:00.001-07:00

http://www.ncbi.nlm.nih.gov/pubmed/7494858?ordinalpos=79&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

http://www.ncbi.nlm.nih.gov/pubmed/16735757?ordinalpos=5&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

2008-04-16T17:38:00.005-07:00

http://www.ncbi.nlm.nih.gov/pubmed/16735757?ordinalpos=5&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

http://www.ncbi.nlm.nih.gov/pubmed/17046694?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

2008-04-16T17:38:00.003-07:00

http://www.ncbi.nlm.nih.gov/pubmed/17046694?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

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http://www.ncbi.nlm.nih.gov/pubmed/8680737?ordinalpos=9&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

2008-04-16T17:38:00.001-07:00

http://www.ncbi.nlm.nih.gov/pubmed/8680737?ordinalpos=9&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Potentiation of electrical and chemical synaptic transmission mediated by endocannabinoids.

2008-01-03T01:31:00.001-08:00

Potentiation of electrical and chemical synaptic transmission mediated by endocannabinoids.

Neuron. 2007 Dec 20;56(6):1034-47

Authors: Cachope R, Mackie K, Triller A, O'Brien J, Pereda AE

Endocannabinoids are well established as inhibitors of chemical synaptic transmission via presynaptic activation of the cannabinoid type 1 receptor (CB(1)R). Contrasting this notion, we show that dendritic release of endocannabinoids mediates potentiation of synaptic transmission at mixed (electrical and chemical) synaptic contacts on the goldfish Mauthner cell. Remarkably, the observed enhancement was not restricted to the glutamatergic component of the synaptic response but also included a parallel increase in electrical transmission. This effect involved the activation of CB(1) receptors and was indirectly mediated via the release of dopamine from nearby varicosities, which in turn led to potentiation of the synaptic response via a cAMP-dependent protein kinase-mediated postsynaptic mechanism. Thus, endocannabinoid release can potentiate synaptic transmission, and its functional roles include the regulation of gap junction-mediated electrical synapses. Similar interactions between endocannabinoid and dopaminergic systems may be widespread and potentially relevant for the motor and rewarding effects of cannabis derivatives.

PMID: 18093525 [PubMed - in process]

Prolonged CNS hyperexcitability in mice after a single exposure to delta-9-tetrahydrocannabinol.

2008-01-03T01:30:00.003-08:00

Prolonged CNS hyperexcitability in mice after a single exposure to delta-9-tetrahydrocannabinol.

Neuropharmacology. 1986 Apr;25(4):441-6

Authors: Karler R, Calder LD, Turkanis SA

A single exposure to delta-9-tetrahydrocannabinol (THC) resulted in a "rebound" hyperexcitability in the CNS in mice, which was assessed in terms of the susceptibility of the CNS to electrically-induced convulsions. The magnitude of the hyperexcitability was dose-related (25-150 mg/kg, i.p.), as measured 24 hr after treatment. The time-course study of the effect indicated a peak-effect at 24 hr after administration of the drug, with a duration of the effect for as long as 196 hr. The time course of the rebound hyperexcitability to THC was compared to that for phenobarbital, which peaked at 48 hr after administration of the drug and returned to the control value by 96 hr. Tolerance developed rapidly to the motor-toxic effect of THC, but after 23 days of daily treatment there was no evidence of tolerance to the rebound hyperexcitability. The functional significance of the hyperexcitable state was assessed in two tests; electrical kindling to minimal convulsions was enhanced, even when the kindling procedure was initiated 120 hr after exposure to the drug; and the anticonvulsant activity of phenytoin was blocked when mice were treated with the anticonvulsant 96 hr after a single exposure to THC. The results suggest that the rebound response from a single exposure to THC represents a functionally significant prolonged increase in excitability of the CNS.

PMID: 3012403 [PubMed - indexed for MEDLINE]

Different cannabinoids exhibit different pharmacological and toxicological properties.

2008-01-03T01:30:00.001-08:00

Different cannabinoids exhibit different pharmacological and toxicological properties.

NIDA Res Monogr. 1987;79:96-107

Authors: Karler R, Turkanis SA

PMID: 3125482 [PubMed - indexed for MEDLINE]

Structure-anticonvulsant activity relationships of cannabidiol analogs.

2008-01-03T01:29:00.005-08:00

Structure-anticonvulsant activity relationships of cannabidiol analogs.

NIDA Res Monogr. 1987;79:48-58

Authors: Martin AR, Consroe P, Kane VV, Shah V, Singh V, Lander N, Mechoulam R, Srebnik M

Cannabidiol (CBD) exhibits anticonvulsant activity in experimental animals and in man. As part of a structure-activity study, analogs were prepared wherein the terpene unit, the aryl unit, and/or the side chain were modified. Thus, several pinenyl and carenyl derivatives, aryl ethers and acetates, and a variety of 1",1"-dialkylhexyl and 1",1"-dialkylheptyl analogs were synthesized. The compounds were evaluated for anti-convulsant activity in seizure susceptible (AGS) rats and for neurotoxicity in the rat rotorod (ROT) test. Comparisons of stereoisomers of CBD and several analogs revealed a general lack of stereoselectivity for anticonvulsant and other CNS properties of this class of compounds.

PMID: 3125480 [PubMed - indexed for MEDLINE]

Anticonvulsant and neurotoxic effects of tetrahydrocannabinol stereoisomers.

2008-01-03T01:29:00.003-08:00

Anticonvulsant and neurotoxic effects of tetrahydrocannabinol stereoisomers.

NIDA Res Monogr. 1987;79:59-66

Authors: Consroe P, Mechoulam R

Enantiomers of delta-6-tetrahydrocannabinol (THC), delta-6-THC-1'', 1''-dimethylheptyl (DMHP), and 7-OH-delta-6-THC-1'',1''-DMHP were assessed for their ability to block audiogenic seizures in genetically epilepsy-prone rats. The stereoisomers were evaluated also for their ability to produce differential neurotoxicity in the rat rotorod (ROT) paradigm. Potency comparisons among the compounds revealed modest to profound stereoselectivity for anticonvulsant and neurotoxic activities, a general increase in both activities with the DMHP and 7-OH modifications of delta-6-THC, and some favorable separation between anticonvulsant and neurotoxic activities with selected THC analogs.

PMID: 2830538 [PubMed - indexed for MEDLINE]

Marijuana use and the risk of new onset seizures.

2008-01-03T01:29:00.001-08:00

Marijuana use and the risk of new onset seizures.

Trans Am Clin Climatol Assoc. 1992;103:176-81

Authors: Brust JC, Ng SK, Hauser AW, Susser M

PMID: 1413377 [PubMed - indexed for MEDLINE]

The autism-epilepsy connection.

2008-01-03T01:28:00.001-08:00

The autism-epilepsy connection.

Epilepsia. 2007;48 Suppl 9:33-5

Authors: Levisohn PM

The high prevalence of epilepsy in children with autism supports a neurobiologic etiology for autism. It remains unclear whether seizures and epileptiform activity on the EEG are causative or comorbid. It is also uncertain if focal epileptiform EEG abnormalities may be associated with stable cognitive impairment. Even less clear is whether these EEG abnormalities can result in the combination of language and social dysfunction seen in autistic spectrum disorders.

PMID: 18047599 [PubMed - in process]

Effect of different patterns of low-frequency stimulation on piriform cortex kindled seizures.

2008-01-03T01:27:00.001-08:00

Effect of different patterns of low-frequency stimulation on piriform cortex kindled seizures.

Neurosci Lett. 2007 Oct 2;425(3):162-6

Authors: Ghorbani P, Mohammad-Zadeh M, Mirnajafi-Zadeh J, Fathollahi Y

Low-frequency stimulation (LFS) is an antiepileptic and antiepileptogenic electrical stimulation. In this study the effect of changes in some LFS (1Hz, monophasic square wave) parameters (intensity, pulse duration and train duration) on piriform cortex kindled seizures was investigated both in fully kindled rats and during kindling acquisition. In fully kindled animals, application of different patterns of LFS immediately before kindling stimulation had no significant effect on seizure parameters. However, daily (15 min) application of LFS (0.1 ms pulse duration at intensity equal to after-discharge threshold (ADT) and 1 ms pulse duration at intensity equal to 1/4 ADT) during inter-seizure interval of 7 days significantly reduced the stage 5 duration of the next kindled seizure. Application of the same two LFS protocols for 3 days and 2 weeks had no effect on seizure parameters. The effect of LFS was also tested using different paradigms during kindling acquisition. When LFS (0.1 and 1 ms pulse duration, intensity equal to ADT and 1/4 ADT) was delivered daily after each kindling stimulation, it could significantly decrease after-discharge duration in various days during kindling development. In this experiment, only LFS with 0.1 ms pulse duration and intensity equal to ADT significantly delayed the appearance of seizure stages 1 and 2. According to obtained results, it may be concluded that in fully kindled rats application of different patterns of LFS before kindling stimulation has no anticonvulsant effect, but it can exert an inhibitory effect when applied during an inter-seizure interval of 7 days. In addition, LFS has antiepileptogenic effect during kindling acquisition. These effects depend on the applied LFS parameters (e.g. intensity, pulse duration and train duration).

PMID: 17868994 [PubMed - indexed for MEDLINE]

A Novel Role for Extracellular Signal-Regulated Kinase in Maintaining Long-Term Memory-Relevant Excitability Changes.

2008-01-03T01:26:00.001-08:00

A Novel Role for Extracellular Signal-Regulated Kinase in Maintaining Long-Term Memory-Relevant Excitability Changes.

J Neurosci. 2007 Nov 14;27(46):12584-12589

Authors: Cohen-Matsliah SI, Brosh I, Rosenblum K, Barkai E

Pyramidal neurons in the piriform cortex from olfactory-discrimination-trained rats show enhanced intrinsic neuronal excitability that lasts for several days after learning. Such enhanced intrinsic excitability is mediated by long-term reduction in the postburst afterhyperpolarization (AHP), which is generated by repetitive spike firing. AHP reduction is attributable to decreased conductance of a calcium-dependent potassium current, the sI(AHP). We have previously shown that such learning-induced AHP reduction is maintained by PKC activation. However, the molecular machinery underlying such long-lasting modulation of intrinsic excitability is yet to be fully described. Here we examine whether the extracellular signal-regulated kinase I/II (ERKI/II) pathway, which is known to be crucial in learning, memory, and synaptic plasticity processes, is instrumental for the long-term maintenance of learning-induced AHP reduction. PD98059 or UO126, which selectively block MEK, the upstream kinase of ERK, increased the AHP in neurons from trained rats but not in neurons from naive and pseudo-trained rats. Consequently, the differences in AHP amplitude and neuronal adaptation between neurons from trained rats and controls were abolished. This effect was not mediated by modulation of basic membrane properties. In accordance with its effect on neuronal excitability, the level of activated ERK in the membranal fraction was significantly higher in piriform cortex samples taken from trained rats. In addition, the PKC activator OAG (1-oleoyl-20acety-sn-glycerol), which was shown to reduce the AHP in neurons from control rats, had no effect on these neurons in the presence of PD98059. Our data show that ERK has a key role in maintaining long-lasting learning-induced enhancement of neuronal excitability.

PMID: 18003837 [PubMed - as supplied by publisher]

Cellular and subcellular localization of Kir2.1 subunits in neurons and glia in piriform cortex with implications for K(+) spatial buffering.

2008-01-03T01:25:00.001-08:00

Cellular and subcellular localization of Kir2.1 subunits in neurons and glia in piriform cortex with implications for K(+) spatial buffering.

J Comp Neurol. 2007 Dec 12;506(5):877-893

Authors: Howe MW, Feig SL, Osting SM, Haberly LB

Potassium channels of the Kir2 family are widely expressed in neurons and glia, where they form strong inwardly rectifying channels. Existing functional hypotheses for these channels in neurons are based on the weak outward conductance, whereas the leading hypothesis for glia, that they promote potassium spatial buffering, is based on inward conductance. Although the spatial buffering hypothesis has been confirmed for Müller glia in retina, many aspects of Kir2 channels that will be required for understanding their functional roles in neurons and other forms of glia have received little or no study. Particularly striking is the paucity of data regarding their cellular and subcellular localization. We address this gap for Kir2.1-containing channels by using light and electron microscopic immunocytochemistry. The analysis was of piriform cortex, a highly epileptogenic area of cerebral cortex, where pyramidal cells have K(+)-selective strong inward rectification like that observed in Müller cells, where Kir2.1 is the dominant Kir2 subunit. Pyramidal cells in adult piriform cortex also lack I(h), the mixed Na(+)-K(+) current that mediates a slower form of strong inward rectification in large pyramidal cells in neocortex and hippocampus. The experiments demonstrated surface expression of Kir2.1-containing channels in astrocytes and in multiple populations of pyramidal and nonpyramidal cells. Findings for astrocytes were not consistent with predictions for K(+) spatial buffering over substantial distance. However, findings for pyramidal cells suggest that they could be a conduit for spatially buffering K(+) when it is highly elevated during seizure. J. Comp. Neurol. 506:877-893, 2008. (c) 2007 Wiley-Liss, Inc.

PMID: 18076085 [PubMed - as supplied by publisher]

Embodying Cultured Networks with a Robotic Drawing Arm.

2007-11-28T03:07:00.003-08:00

Embodying Cultured Networks with a Robotic Drawing Arm.

Conf Proc IEEE Eng Med Biol Soc. 2007;1:2996-2999

Authors: Bakkum DJ, Chao ZC, Gamblen P, Ben-Ary G, Shkolnik AG, Demarse TB, Potter SM

The advanced and robust computational power of the brain is shown by the complex behaviors it produces. By embodying living cultured neuronal networks with a robotic or simulated animal (animat) and situating them within an environment, we study how the basic principles of neuronal network communication can culminate into adaptive goal-directed behavior. We engineered a closed-loop biological-robotic drawing machine and explored sensory-motor mappings and training. Preliminary results suggest that real-time performance-based feedback allowed an animat to draw in desired directions. This approach may help instruct the future design of artificial neural systems and of the algorithms to interface sensory and motor prostheses with the brain.

PMID: 18002625 [PubMed - as supplied by publisher]

How do TTX and AP5 affect the post-recovery neuronal network activity synchronization?

2007-11-28T03:07:00.001-08:00

How do TTX and AP5 affect the post-recovery neuronal network activity synchronization?

Conf Proc IEEE Eng Med Biol Soc. 2007;1:3012-3015

Authors: Esposti F, Signorini MG, Lamanna J, Gullo F, Wanke E

A lot of methods were created in last decade for the spatio-temporal analysis of multi-electrode array (MEA) neuronal data sets. The greater part of these methods does not consider the network as a whole but performs an analysis channel by channel. In this paper we illustrate how a very simple approach that considers the total network activity, is able to show interesting neuronal network features. In particular we perform two different analyses: a connectivity examination studying networks at different days in vitro and an analysis of the long period effects of the administration of two common neuro-active drugs, i.e. TTX and AP5. Our analysis is performed considering burst topology, i.e. cataloguing network bursts as Global (if they involve more than the 25% of the MEA channels) or Local (if less that 25%). This division allows, in the first analysis, to understand the network connectivity (increasing from div 1 to 6) and decreasing till reaching a plateau (from div 6 to 10). The second analysis highlights a substantial difference between the long period effects of TTX and AP5. While TTX induces a massive Global activity explosion, sign of a prolonged inhibitory synapse depression, AP5 shows only a modest Local activity increase, mark of the low effect of NMDA receptors on a mature neuronal network without inputs.

PMID: 18002629 [PubMed - as supplied by publisher]

Different cannabinoids exhibit different electrophysiological properties.

2007-11-28T03:05:00.001-08:00

Different cannabinoids exhibit different electrophysiological properties.

NIDA Res Monogr. 1987;79:67-81

Authors: Turkanis SA, Karler R

PMID: 3125481 [PubMed - indexed for MEDLINE]

Marijuana use and the risk of new onset seizures.

2007-11-28T03:04:00.009-08:00

Marijuana use and the risk of new onset seizures.

Trans Am Clin Climatol Assoc. 1992;103:176-81

Authors: Brust JC, Ng SK, Hauser AW, Susser M

PMID: 1413377 [PubMed - indexed for MEDLINE]

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[Results of a standardized survey on the medical use of cannabis products in the German-speaking area]

2007-11-28T03:04:00.007-08:00

[Results of a standardized survey on the medical use of cannabis products in the German-speaking area]

Forsch Komplementarmed. 1999 Oct;6 Suppl 3:28-36

Authors: Schnelle M, Grotenhermen F, Reif M, Gorter RW

The plant Cannabis sativa has a long history of medical use in the treatment of pain and spasms, the promotion of sleep, and the suppression of nausea and vomiting. However, in the early 70s cannabis was classified in the Narcotic Acts in countries all over the world as having no therapeutic benefit; therefore, it cannot be prescribed by physicians or dispensed by pharmacists. In the light of this contradictory situation an increasing number of patients practices a self-prescription with cannabis products for relieving a variety of symptoms. An anonymous standardized survey of the medical use of cannabis and cannabis products of patients in Germany, Austria and Switzerland was conducted by the Association for Cannabis as Medicine (Cologne, Germany). During about one year 170 subjects participated in this survey; questionnaires of 128 patients could be included into the evaluation. 68% of these participants were males, 32% females, with a total mean age of 37.5 (+/- 9.6) years. The most frequently mentioned indications for medicinal cannabis use were depression (12.0%), multiple sclerosis (10.8%), HIV-infection (9.0%), migraine (6.6%), asthma (6.0%), back pain (5.4%), hepatitis C (4. 8%), sleeping disorders (4.8%), epilepsy (3.6%), spasticity (3.6%), headache (3.6%), alcoholism (3.0%), glaucoma (3.0%), nausea (3.0%), disk prolapse (2.4%), and spinal cord injury (2.4%). The majority of patients used natural cannabis products such as marihuana, hashish and an alcoholic tincture; in just 5 cases dronabinol (Marinol) was taken by prescription. About half of the 128 participants of the survey (52.4%) had used cannabis as a recreational drug before the onset of their illness. To date 14.3% took cannabis orally, 49.2% by inhalation and in 36.5% of cases both application modes were used. 72.2% of the patients stated the symptoms of their illness to have 'much improved' after cannabis ingestion, 23.4% stated to have 'slightly improved', 4.8% experienced 'no change' and 1.6% described that their symptoms got 'worse'. Being asked for the satisfaction with their therapeutic use of cannabis 60.8% stated to be 'very satisfied', 24.0% 'satisfied', 11.2% 'partly satisfied' and 4.0% were 'not satisfied'. 70.8% experienced no side effects, 26.4% described 'moderate' and 3.3% 'strong' side effects. 84.1% of patients have not felt any need for dose escalation during the last 3 months, 11.0% had to increase their cannabis dose 'moderately' and 4.8% 'strongly' in order to maintain the therapeutic effects. Thus, this survey demonstrates a successful use of cannabis products for the treatment of a multitude of various illnesses and symptoms. This use was usually accompanied only by slight and in general acceptable side effects. Because the patient group responding to this survey is presumably highly selected, no conclusions can be drawn about the quantity of wanted and unwanted effects of the medicinal use of the hemp plant for particular indications. Copyright Copyright 1999 S. Karger GmbH, Freiburg

PMID: 10575286 [PubMed - indexed for MEDLINE]

Therapeutic aspects of cannabis and cannabinoids.

2007-11-28T03:04:00.005-08:00

Therapeutic aspects of cannabis and cannabinoids.

Br J Psychiatry. 2001 Feb;178:107-15

Authors: Robson P

BACKGROUND: Review commissioned in 1996 by the Department of Health (DOH). AIMS: Assess therapeutic profile of cannabis and cannabinoids. METHOD: Medline search, references supplied by DOH and others, and personal communications. RESULTS AND CONCLUSIONS: Cannabis and some cannabinoids are effective anti-emetics and analgesics and reduce intra-ocular pressure. There is evidence of symptom relief and improved well-being in selected neurological conditions, AIDS and certain cancers. Cannabinoids may reduce anxiety and improve sleep. Anticonvulsant activity requires clarification. Other properties identified by basic research await evaluation. Standard treatments for many relevant disorders are unsatisfactory. Cannabis is safe in overdose but often produces unwanted effects, typically sedation, intoxication, clumsiness, dizziness, dry mouth, lowered blood pressure or increased heart rate. The discovery of specific receptors and natural ligands may lead to drug developments. Research is needed to optimise dose and route of administration, quantify therapeutic and adverse effects, and examine interactions.

PMID: 11157423 [PubMed - indexed for MEDLINE]

Anticonvulsant activity of N-palmitoylethanolamide, a putative endocannabinoid, in mice.

2007-11-28T03:04:00.003-08:00

Anticonvulsant activity of N-palmitoylethanolamide, a putative endocannabinoid, in mice.

Epilepsia. 2001 Mar;42(3):321-7

Authors: Lambert DM, Vandevoorde S, Diependaele G, Govaerts SJ, Robert AR

PURPOSE: The purpose of this study was to evaluate in mice the anticonvulsant potential of N-palmitoylethanolamide, a putative endocannabinoid that accumulates in the body during inflammatory processes. METHODS: N-palmitoylethanolamide was injected intraperitoneally (i.p.) in mice and evaluated for anticonvulsant activity [in maximal electroshock seizure (MES) and chemical-induced convulsions] and for neurologic impairment (rotorod). It was compared with anandamide and with different palmitic acid analogues as well as with reference anticonvulsants (AEDs) injected under the same conditions. RESULTS: The MES test showed, after i.p. administration to mice, that N-palmitoy]ethanolamide had an median effective dose (ED50) value comparable to that of phenytoin (PHT; 8.9 and 9.2 mg/kg, respectively). In the subcutaneous pentylenetetrazol test and in the 3-mercaptropropionic acid test, it was effective only against tonic convulsions. N-palmitoylethanolamide was devoid of neurologic impairment < or = 250 mg/kg, yielding a high protective index. CONCLUSIONS: N-palmitoylethanolamide, an endogenous compound with antiinflammatory and analgesic activities, is a potent AED in mice. Its precise mechanism of action remains to be elucidated.

PMID: 11442148 [PubMed - indexed for MEDLINE]

Direct inhibition of T-type calcium channels by the endogenous cannabinoid anandamide.

2007-11-28T03:04:00.001-08:00

Direct inhibition of T-type calcium channels by the endogenous cannabinoid anandamide.

EMBO J. 2001 Dec 17;20(24):7033-40

Authors: Chemin J, Monteil A, Perez-Reyes E, Nargeot J, Lory P

Low-voltage-activated or T-type Ca(2+) channels (T-channels) are widely expressed, especially in the central nervous system where they contribute to pacemaker activities and are involved in the pathogenesis of epilepsy. Proper elucidation of their cellular functions has been hampered by the lack of selective pharmacology as well as the absence of generic endogenous regulations. We report here that both cloned (alpha(1G), alpha(1H) and alpha(1I) subunits) and native T-channels are blocked by the endogenous cannabinoid, anandamide. Anandamide, known to exert its physiological effects through cannabinoid receptors, inhibits T-currents independently from the activation of CB1/CB2 receptors, G-proteins, phospholipases and protein kinase pathways. Anandamide appears to be the first endogenous ligand acting directly on T-channels at submicromolar concentrations. Block of anandamide membrane transport by AM404 prevents T-current inhibition, suggesting that anandamide acts intracellularly. Anandamide preferentially binds and stabilizes T-channels in the inactivated state and is responsible for a significant decrease of T-currents associated with neuronal firing activities. Our data demonstrate that anandamide inhibition of T-channels can regulate neuronal excitability and account for CB receptor-independent effects of this signaling molecule.

PMID: 11742980 [PubMed - indexed for MEDLINE]

Psychostimulants and epilepsy.

2007-11-28T03:03:00.007-08:00

Psychostimulants and epilepsy.

Epilepsia. 2002;43 Suppl 2:28-31

Authors: Zagnoni PG, Albano C

PURPOSE: The aim of this article is to review the literature on the effects of psychostimulants in epileptic subjects in order to reach a consensus statement regarding the use or abuse of these substances. METHODS: Psychostimulant substances have been considered the drugs that share the ability to produce excitation of the CNS leading to convulsions. The stimulation may be at cortical, brainstem, or spinal levels. In this article, the following cortical stimulants are analyzed and discussed: cocaine, amphetamine and related agents, caffeine, cannabinoids, and psychedelic drugs. This review is based on research done using pharmacological textbooks and Medline. RESULTS: The use of cocaine is associated with the occurrence of seizures. The reported frequency varies from 1% to 40% of addicted subjects, based on the typology of the considered study. Amphetamines and related drugs rarely induce epileptic seizures at therapeutic doses, but seizures may occur after the first dosing. Caffeine at high doses may induce epileptic seizures because of its adenosine receptor-antagonizing properties. Marijuana, at variance with other psychostimulants, owing to its serotonin-mediated anticonvulsant action, could have a medical use for the treatment of epilepsy. Psychedelic compounds rarely induce epileptic seizures, but the most common clinical CNS complication after ingestion of ecstasy is the occurrence of seizures. CONCLUSIONS: The use of psychostimulants, except for marijuana, can induce single or multiple seizures in healthy subjects.

PMID: 11903480 [PubMed - indexed for MEDLINE]

Medical efficacy of cannabinoids and marijuana: a comprehensive review of the literature.

2007-11-28T03:03:00.005-08:00

Medical efficacy of cannabinoids and marijuana: a comprehensive review of the literature.

J Palliat Care. 2002;18(2):111-22

Authors: Bagshaw SM, Hagen NA

PMID: 12164099 [PubMed - indexed for MEDLINE]

Evidence for a physiological role of endocannabinoids in the modulation of seizure threshold and severity.

2007-11-28T03:03:00.003-08:00

Evidence for a physiological role of endocannabinoids in the modulation of seizure threshold and severity.

Eur J Pharmacol. 2002 Oct 11;452(3):295-301

Authors: Wallace MJ, Martin BR, DeLorenzo RJ

The anticonvulsant effect of cannabinoids has been shown to be mediated through activation of the cannabinoid CB(1) receptor. This study was initiated to evaluate the effects of endogenously occurring cannabinoids (endocannabinoids) on seizure severity and threshold. The anticonvulsant effect of the endocannabinoid, arachidonylethanolamine (anandamide), was evaluated in the maximal electroshock seizure model using male CF-1 mice and was found to be a fully efficacious anticonvulsant (ED(50)=50 mg/kg i.p.). The metabolically stable analog of anandamide, (R)-(20-cyano-16,16-dimetyldocosa-cis-5,8,11,14-tetraenoyl)-1'-hydroxy-2'-propylamine (O-1812), was also determined to be a potent anticonvulsant in the maximal electroshock model (ED(50)=1.5 mg/kg i.p.). Furthermore, pretreatment with the cannabinoid CB(1) receptor specific antagonist N-(piperidin-1-yl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamidehydrochloride (SR141716A) completely abolished the anticonvulsant effect of anandamide as well as O-1812 (P< or =0.01, Fisher exact test), indicating a cannabinoid CB(1) receptor-mediated anticonvulsant mechanism for both endocannabinoid compounds. Additionally, the influence of cannabinoid CB(1) receptor endogenous tone on maximal seizure threshold was assessed using SR141716A alone. Our data show that SR141716A (10 mg/kg i.p.) significantly reduced maximal seizure threshold (CC(50)=14.27 mA) compared to vehicle-treated animals (CC(50)=17.57 mA) (potency ratio=1.23, lower confidence limit=1.06, upper confidence limit=1.43), indicating the presence of an endogenous cannabinoid tone that modulates seizure activity. These data demonstrate that anandamide and its analog, O-1812, are anticonvulsant in a whole animal model and further implicate the cannabinoid CB(1) receptor as a major endogenous site of seizure modulation.

PMID: 12359270 [PubMed - indexed for MEDLINE]

Cannabinoid receptor-1 activation suppresses inhibitory synaptic activity in human dentate gyrus.

2007-11-28T03:03:00.001-08:00

Cannabinoid receptor-1 activation suppresses inhibitory synaptic activity in human dentate gyrus.

Neuropharmacology. 2003 Jul;45(1):116-21

Authors: Nakatsuka T, Chen HX, Roper SN, Gu JG

In spite of their popular uses as recreational drugs and their potential therapeutic uses, little direct information has been obtained about the synaptic effects of cannabinoids in the human brain. In the present study, patch-clamp recordings were performed on granule cells of the human dentate gyrus and the effects of cannabinoid receptor-1 (CB1) activation on inhibitory synaptic activity were examined. Activation of CB1 receptors by WIN55212-2 significantly suppressed both frequency and amplitude of spontaneous inhibitory synaptic currents (IPSCs) to about 50% of control. The suppressive effects were completely abolished in the presence of the CB1 receptor antagonist, AM251. WIN55212-2 also suppressed evoked IPSCs. However, neither frequency nor amplitude of miniature IPSCs were affected by WIN55212-2. These results provide electrophysiological evidence for the role of CB1 receptors in modulating inhibitory activity in human dentate gyrus.

PMID: 12814664 [PubMed - indexed for MEDLINE]

Hedonic-specific activity in piriform cortex during odor imagery mimics that during odor perception.

2007-11-28T03:01:00.003-08:00

Hedonic-specific activity in piriform cortex during odor imagery mimics that during odor perception.

J Neurophysiol. 2007 Oct 3;

Authors: Bensafi M, Sobel N, Khan RM

Whereas it is known that visual imagery is accompanied by activity in visual cortical areas, including primary visual cortex, whether olfactory imagery exists remains controversial. Here we asked whether cue-dependent olfactory imagery was similarly accompanied by activity in olfactory cortex, and in particular whether hedonic-specific patterns of activity evident in olfactory perception would also be present during olfactory imagery. We used functional magnetic resonance imaging to measure activity in subjects who alternated between smelling and imagining pleasant and unpleasant odors. Activity induced by imagining odors mimicked that induced by perceiving real odorants, not only in the particular brain regions activated, but also in its hedonic-specific pattern. For both real and imagined odors, unpleasant stimuli induced greater activity than pleasant stimuli in the left frontal portion of piriform cortex and left insula. These findings combine with findings from other modalities to suggest activation of primary sensory cortical structures during mental imagery of sensory events.

PMID: 17913994 [PubMed - as supplied by publisher]

Imaging of odor perception delineates functional disintegration of the limbic circuits in mesial temporal lobe epilepsy.

2007-11-28T03:01:00.001-08:00

Imaging of odor perception delineates functional disintegration of the limbic circuits in mesial temporal lobe epilepsy.

Neuroimage. 2007 Sep 14;

Authors: Ciumas C, Lindström P, Bernard A, Savic I

Metabolic and neuro-receptor abnormalities within the extrafocal limbic circuits are established in mesial temporal lobe epilepsy (MTLE). However, very little is known about how these circuits process external stimuli. We tested whether odor activation can help delineate limbic functional disintegration in MTLE, and measured cerebral blood flow with PET during birhinal smelling of familiar and unfamiliar odors, using smelling of odorless air as the baseline condition. Patients with MTLE (13 left-sided, 10 right-sided) and 21 controls were investigated. In addition to odor activation, the analysis included functional connectivity, using right and left piriform cortex as seed regions. Healthy controls activated the amygdala, piriform, anterior insular, and cingulate cortices on both sides. Smelling of familiar odors engaged, in addition, the right parahippocampus, and the left Brodmann Area (BA) 44, 45, 47. Patients failed to activate the amygdala, piriform and the anterior insular cortex in the epileptogenic hemisphere. Furthermore, those with left MTLE did not activate the left BA 44, 45 and 47 with familiar odors, which they perceived as less familiar than controls. Congruent with the activation data each seed region was in patients functionally disconnected with the contralateral amygdala+piriform+insular cortex. The functional disintegration in patients exceeded the reduced activation, and included the contralateral temporal neocortex, and in subjects with right MTLE also the right orbitofrontal cortex. Imaging of odor perception may be used to delineate functional disintegration of the limbic networks in MTLE. It shows an altered response in several regions, which may underlie some interictal behavioral problems associated with this condition.

PMID: 17951077 [PubMed - as supplied by publisher]

Perturbed chloride homeostasis and GABAergic signaling in human temporal lobe epilepsy.

2007-11-15T03:57:00.003-08:00

Perturbed chloride homeostasis and GABAergic signaling in human temporal lobe epilepsy.

J Neurosci. 2007 Sep 12;27(37):9866-73

Authors: Huberfeld G, Wittner L, Clemenceau S, Baulac M, Kaila K, Miles R, Rivera C

Changes in chloride (Cl-) homeostasis may be involved in the generation of some epileptic activities. In this study, we asked whether Cl- homeostasis, and thus GABAergic signaling, is altered in tissue from patients with mesial temporal lobe epilepsy associated with hippocampal sclerosis. Slices prepared from this human tissue generated a spontaneous interictal-like activity that was initiated in the subiculum. Records from a minority of subicular pyramidal cells revealed depolarizing GABA(A) receptor-mediated postsynaptic events, indicating a perturbed Cl- homeostasis. We assessed possible contributions of changes in expression of the potassium-chloride cotransporter KCC2. Double in situ hybridization showed that mRNA for KCC2 was absent from approximately 30% of CaMKIIalpha (calcium/calmodulin-dependent protein kinase IIalpha)-positive subicular pyramidal cells. Combining intracellular recordings with biocytin-filled electrodes and KCC2 immunochemistry, we observed that all cells that were hyperpolarized during interictal events were immunopositive for KCC2, whereas the majority of depolarized cells were immunonegative. Bumetanide, at doses that selectively block the chloride-importing potassium-sodium-chloride cotransporter NKCC1, produced a hyperpolarizing shift in GABA(A) reversal potentials and suppressed interictal activity. Changes in Cl- transporter expression thus contribute to human epileptiform activity, and molecules acting on these transporters may be useful antiepileptic drugs.

PMID: 17855601 [PubMed - indexed for MEDLINE]

Chaos, brain and divided consciousness.

2007-11-15T03:57:00.001-08:00

Chaos, brain and divided consciousness.

Acta Univ Carol Med Monogr. 2007;153:9-80

Authors: Bob P

Modern trends in psychology and cognitive neuroscience suggest that applications of nonlinear dynamics, chaos and self-organization seem to be particularly important for research of some fundamental problems regarding mind-brain relationship. Relevant problems among others are formations of memories during alterations of mental states and nature of a barrier that divides mental states, and leads to the process called dissociation. This process is related to a formation of groups of neurons which often synchronize their firing patterns in a unique spatial maner. Central theme of this study is the relationship between level of moving and oscilating mental processes and their neurophysiological substrate. This opens a question about principles of organization of conscious experiences and how these experiences arise in the brain. Chaotic self-organization provides a unique theoretical and experimental tool for deeper understanding of dissociative phenomena and enables to study how dissociative phenomena can be linked to epileptiform discharges which are related to various forms of psychological and somatic manifestations. Organizing principles that constitute human consciousness and other mental phenomena from this point of view may be described by analysis and reconstruction of underlying dynamics of psychological or psychophysiological measures. These nonlinear methods in this study were used for analysis of characteristic changes in EEG and bilateral electrodermal activity (EDA) during reliving of dissociated traumatic and stressful memories and during psychopathological states. Analysis confirms a possible role of chaotic transitions in the processing of dissociated memory. Supportive finding for a possible chaotic process related to dissociation found in this study represent also significant relationship of dissociation, epileptiform discharges measured by typical psychopathological manifestations and characteristic laterality changes in bilateral EDA in patients with schizophrenia and depression. Increased level of psychopathological symptoms indicates close relationship to the right-left EDA asymmetry and asymmetry of information entropy calculated by non-linear recurrence quantification analysis of EDA records. Because epileptiform activity has specific chaotic behaviour and calculated information entropy from EDA records reflects the complexity of the deterministic structure in the system there is a relevant assumption that unilaterally increased complexity may produce interhemispheric disbalance and increased chaoticity which hypothetically may serve as a dynamic source of epileptiform discharges related to trauma induced kindling mechanism. Specific form of chaotic inner organization which cannot be explained only as a consequence of external causality support also psychophysiological data that lead to the so-called self-organizing theory of dreaming by Kahn and Hobson. This study suggests that self-organizing theory of dreaming is particularly important with respect to problem of memory formation and processing during dissociative states characteristic for dreams. Recent data and also findings of this study support the research utility of chaos theory in psychology and neuroscience, and also its conceptual view of dynamic ordering factors and self-organization underlying psychological processes and brain physiology.

PMID: 17867519 [PubMed - indexed for MEDLINE]

Enhanced astrocytic Ca2+ signals contribute to neuronal excitotoxicity after status epilepticus.

2007-11-15T03:56:00.003-08:00

Enhanced astrocytic Ca2+ signals contribute to neuronal excitotoxicity after status epilepticus.

J Neurosci. 2007 Oct 3;27(40):10674-84

Authors: Ding S, Fellin T, Zhu Y, Lee SY, Auberson YP, Meaney DF, Coulter DA, Carmignoto G, Haydon PG

Status epilepticus (SE), an unremitting seizure, is known to cause a variety of traumatic responses including delayed neuronal death and later cognitive decline. Although excitotoxicity has been implicated in this delayed process, the cellular mechanisms are unclear. Because our previous brain slice studies have shown that chemically induced epileptiform activity can lead to elevated astrocytic Ca2+ signaling and because these signals are able to induce the release of the excitotoxic transmitter glutamate from these glia, we asked whether astrocytes are activated during status epilepticus and whether they contribute to delayed neuronal death in vivo. Using two-photon microscopy in vivo, we show that status epilepticus enhances astrocytic Ca2+ signals for 3 d and that the period of elevated glial Ca2+ signaling is correlated with the period of delayed neuronal death. To ask whether astrocytes contribute to delayed neuronal death, we first administered antagonists which inhibit gliotransmission: MPEP [2-methyl-6-(phenylethynyl)pyridine], a metabotropic glutamate receptor 5 antagonist that blocks astrocytic Ca2+ signals in vivo, and ifenprodil, an NMDA receptor antagonist that reduces the actions of glial-derived glutamate. Administration of these antagonists after SE provided significant neuronal protection raising the potential for a glial contribution to neuronal death. To test this glial hypothesis directly, we loaded Ca2+ chelators selectively into astrocytes after status epilepticus. We demonstrate that the selective attenuation of glial Ca2+ signals leads to neuronal protection. These observations support neurotoxic roles for astrocytic gliotransmission in pathological conditions and identify this process as a novel therapeutic target.

PMID: 17913901 [PubMed - in process]

A pilot study transitioning children onto levetiracetam monotherapy to improve language dysfunction associated with benign rolandic epilepsy.

2007-11-15T03:56:00.001-08:00

A pilot study transitioning children onto levetiracetam monotherapy to improve language dysfunction associated with benign rolandic epilepsy.

Epilepsy Behav. 2007 Oct 11;

Authors: Kossoff EH, Los JG, Boatman DF

Benign rolandic epilepsy (BRE) and Landau-Kleffner syndrome (LKS) are similar epilepsy syndromes with sleep-accentuated epileptiform activity, sporadic seizures, and language dysfunction. Levetiracetam has been associated with improved language function in LKS and seizure reduction in BRE. We hypothesized levetiracetam would improve language function in children with BRE. A pilot study was performed with six children (aged 6-12) with BRE and evidence of impaired auditory comprehension and verbal memory. Children were transitioned from their current anticonvulsant to 40 mg/kg/day levetiracetam over a 2-week period and retested at 6 months. At 6 months, three of four children with baseline auditory comprehension impairments performed normally (P=0.06), and five had improved auditory verbal memory (P=0.08). Seizures improved in five, decreasing from 2.7 to 1.0 seizure per 6 months (P=0.11). Results from this pilot study suggest that levetiracetam may have a beneficial effect on language in children with BRE.

PMID: 17936689 [PubMed - as supplied by publisher]

Inhibitory interneurons in the piriform cortex.

2007-11-15T03:55:00.001-08:00

Inhibitory interneurons in the piriform cortex.

Clin Exp Pharmacol Physiol. 2007 Oct;34(10):1064-9

Authors: Suzuki N, Bekkers JM

1. The piriform cortex (PC) is the largest subdivision of the olfactory cortex and the first cortical destination of olfactory information. Despite the relatively simple anatomy of the PC and its obvious appeal as a model system for the study of cortical sensory processing, there are many outstanding questions about its basic cell physiology. In the present article, we review what is known about GABAergic inhibitory interneurons in the PC. 2. The GABA-containing neurons in the PC are morphologically diverse, ranging from small neurogliaform cells to large multipolar forms. Some of these classes are distributed across all three main layers of the PC, whereas others have a more restricted laminar expression. 3. Distinct and overlapping populations of GABAergic basket cells in Layers II and III of the PC express different combinations of calcium-binding proteins and neuropeptides. Few Layer I interneurons express any of the molecular markers so far examined. 4. The intrinsic firing properties of one or two types of putative PC interneurons have been measured and inhibitory post-synaptic responses have been recorded in PC pyramidal cells following extracellular stimulation. However, little is known about the physiology of the subtypes of interneurons identified. 5. In view of the likely importance of PC interneurons in olfactory learning, olfactory coding and epileptogenesis, further investigation of their properties is likely to be highly informative.

PMID: 17714095 [PubMed - indexed for MEDLINE]

Early Telencephalic Migration Topographically Converging in the Olfactory Cortex.

2007-11-15T03:54:00.003-08:00

Early Telencephalic Migration Topographically Converging in the Olfactory Cortex.

Cereb Cortex. 2007 Sep 17;

Authors: García-Moreno F, López-Mascaraque L, de Carlos JA

Neurons that participate in the olfactory system arise in different areas of the developing mouse telencephalon. The generation of these different cell populations and their tangential migration into the olfactory cortex (OC) was tracked by tracer injection and in toto embryo culture. Cells originating in the dorsal lateral ganglionic eminence (LGE) migrate tangentially along the anteroposterior axis to settle in the piriform cortex (PC). Those originating in the ventral domain of this structure occupy the thickness of the olfactory tubercle (OT), whereas cells from the rostral LGE migrate tangentially into the most anterior telencephalon, at the level of the prospective olfactory bulb (pOB). Neurons from the dorsal telencephalon migrate ventrally, bordering the PC, toward olfactory structures. Two cell populations migrate tangentially from the rostromedial telencephalic wall to the OT and the PC, passing through the ventromedial and dorsolateral face of the telencephalon. Some cells from the germinative area of the rostral telencephalon, at the level of the septoeminential sulcus, migrate rostrally to the pOB or caudally to the OC. Thus, we demonstrate multiple telencephalic origins for the first olfactory neurons and each population following different migratory routes to colonize the OC according to an accurate topographic map.

PMID: 17878174 [PubMed - as supplied by publisher]

Distinct effects of anterior pyriform cortex and the lateral hypothalamus lesions on protein intake in rats.

2007-11-15T03:54:00.001-08:00

Distinct effects of anterior pyriform cortex and the lateral hypothalamus lesions on protein intake in rats.

J Med Invest. 2007 Aug;54(3-4):255-60

Authors: Nakao R, Ozaki E, Hasegawa M, Kondo A, Uezu K, Hirasaka K, Nikawa T, Kishi K

Several specific locations in brain, including pyriform cortex and hypothalamus, are associated with regulation of food intake. Although lesions of these locations significantly alter food intake, their involvement in the selection of macronutrients is not well characterized. In this study, we examined distinct effects of anterior pyriform cortex (APC) and lateral hypothalamus (LH) lesions on protein intake in rats. The APC or LH of male adult rats were lesioned by treatment with kainic acid, and the rats were then given free access to two kinds of casein diets containing high (60%) and low (5%) protein. Total energy content of these diets was kept constant by changing the carbohydrate content. Following the APC lesions, body weight and food intake decreased, but returned to control levels on day 13 and day 4, respectively. APC lesions did not change the ratio of protein intake. In contrast, LH lesions disturbed body weight gain and the selection of a high protein diet for at least two weeks, although food intake returned to control levels by day 2. Our results suggest that LH, but not APC, may play an important role in the selection of protein intake in rats.

PMID: 17878674 [PubMed - indexed for MEDLINE]

Muscarinic receptor activation modulates granule cell excitability and potentiates inhibition onto mitral cells in the rat olfactory bulb.

2007-11-15T03:53:00.001-08:00

Muscarinic receptor activation modulates granule cell excitability and potentiates inhibition onto mitral cells in the rat olfactory bulb.

J Neurosci. 2007 Oct 10;27(41):10969-81

Authors: Pressler RT, Inoue T, Strowbridge BW

The olfactory bulb is a second-order brain region that connects sensory neurons with cortical areas. However, the olfactory bulb does not appear to play a simple relay role and is subject instead to extensive local and extrinsic synaptic influences. Prime among the external, or centrifugal, inputs is the dense cholinergic innervation from the basal forebrain, which terminates in both the granule cell and plexiform layers. Cholinergic inputs to the bulb have been implicated in olfactory working memory tasks in rodents and may be related to olfactory deficits reported in people with neurodegenerative disorders that involve basal forebrain neurons. In this study, we use whole-cell recordings from acute rat slices to demonstrate that one function of this input is to potentiate the excitability of GABAergic granule cells and thereby modulate inhibitory drive onto mitral cells. This increase in granule cell excitability is mediated by a concomitant decrease in the normal afterhyperpolarization response and augmentation of an afterdepolarization, both triggered by pirenzepine-sensitive M1 receptors. The afterdepolarization was dependent on elevations in intracellular calcium and appeared to be mediated by a calcium-activated nonselective cation current (I(CAN)). Near firing threshold, depolarizing inputs could evoke quasipersistent firing characterized by irregular discharges that lasted, on average, for 2 min. In addition to regulating the excitability of the primary interneuronal subtype in the bulb, M1 receptors regulate the degree of adaptation that occurs during repetitive sniffing-like inputs and may therefore play a critical role in regulating short-term plasticity in the olfactory system.

PMID: 17928438 [PubMed - indexed for MEDLINE]

Synchronized spontaneous spikes on multi-electrode array show development of cultured neuronal network.

2007-10-26T10:34:00.003-07:00

Synchronized spontaneous spikes on multi-electrode array show development of cultured neuronal network.

Conf Proc IEEE Eng Med Biol Soc. 2005;2:2134-7

Authors: Li X, Zhou W, Liu M, Luo Q

Spontaneous firing play an important role in development of neuronal network. Activity-dependent modification of synaptic efficacy is widely recognized as a cellular basis of learning, memory, and development plasticity. Little is known of the activity-dependent modification of the synchronized spontaneous firing of the hippocampal networks. Long-term recording of spontaneous activity in cultured hippocampal neuronal networks was carried out using substrates containing multi-electrode array (MEA). Spontaneous uncorrelated firing appeared within a week and transformed progressively into synchronized pattern. During the development, these synchronized firings became into oscillation pattern and the synchronization has little change. By paired stimulation from adjacent electrodes in the network, the synchronized firing form a larger network burst. These results suggest that synchronized spontaneous spikes show the development of neuronal network and electronical stimulation could change the development.

PMID: 17282651 [PubMed - in process]

Multiresolution bayesian detection of multiunit extracellular spike waveforms in multichannel neuronal recordings.

2007-10-26T10:34:00.001-07:00

Multiresolution bayesian detection of multiunit extracellular spike waveforms in multichannel neuronal recordings.

Conf Proc IEEE Eng Med Biol Soc. 2005;1:141-4

Authors: Suhail Y, Oweiss K

We describe multiresolution Bayesian tests for spike detection in multielectrode recordings. We derive results for single channel and multi electrode data, and show that the use of the array model substantially improves the detection performance. The effect of signal and noise spatial correlation characteristics is also discussed. Our approach focuses on blind signal detection without any assumptions about the underlying signal parameters. It is therefore suitable for chronic recordings with electrode arrays where typically temporal and spatial nonstationarity of the extracellular waveforms complicates the estimation of the true action potential.

PMID: 17282131 [PubMed - in process]

Modeling the Nonlinear Dynamic Interactions of the Lateral and the Medial Perforant Path of the Hippocampal Dentate Gyrus.

2007-10-26T10:30:00.001-07:00

Modeling the Nonlinear Dynamic Interactions of the Lateral and the Medial Perforant Path of the Hippocampal Dentate Gyrus.

Conf Proc IEEE Eng Med Biol Soc. 2006;1:5539-5542

Authors: Dimoka A, Courellis SH, Marmarelis VZ, Berger TW

We present a new method to characterize the nonlinearities resulting from the co-activity of two pathways that converge on a common postsynaptic element. We investigated the nonlinear dynamic interactions between the lateral perforant pathway (LPP) and the medial perforant pathway (MPP) of the hippocampal dentate gyms, and the effects of these cross-pathway interactions on granule cell output. A third order Volterra-Poisson modeling approach was implemented to capture the interactions between the two pathways. The kernels presented pathway specific signatures as they capture the nonlinear dynamics of each pathway individually in the form of self-kernels, and the nonlinear interactions between the two pathways in the form of cross-kernels. Data were collected in-vitro from acute slices of adult rats via a multi-electrode array recording system. The stimuli were dual-site random impulse trains with Poisson distributed inter-impulse intervals. The recorded responses from the granule cells were population spikes, simplified as discrete impulses with variable amplitudes. Our results indicated that the third order nonlinear interactions between the LPP and the MPP needs to be included in the model in order to achieve adequate predictive accuracy and indicate that this approach can be generalized to complex interactions between distinct inputs to the same set of neurons.

PMID: 17946313 [PubMed - as supplied by publisher]

Imaging of odor perception delineates functional disintegration of the limbic circuits in mesial temporal lobe epilepsy.

2007-10-26T10:25:00.001-07:00

Imaging of odor perception delineates functional disintegration of the limbic circuits in mesial temporal lobe epilepsy.

Neuroimage. 2007 Sep 14;

Authors: Ciumas C, Lindström P, Bernard A, Savic I

PMID: 17951077 [PubMed - as supplied by publisher]

Rhythmic Spontaneous Activity in the Piriform Cortex.

2007-10-26T10:21:00.003-07:00

Rhythmic Spontaneous Activity in the Piriform Cortex.

Cereb Cortex. 2007 Oct 8;

Authors: Sanchez-Vives MV, Descalzo VF, Reig R, Figueroa NA, Compte A, Gallego R

Slow spontaneous rhythmic activity is generated and propagates in neocortical slices when bathed in an artificial cerebrospinal fluid with ionic concentrations similar to the ones in vivo. This activity is extraordinarily similar to the activation of the cortex in physiological conditions (e.g., slow-wave sleep), thus representing a unique in vitro model to understand how cortical networks maintain and control ongoing activity. Here we have characterized the activity generated in the olfactory or piriform cortex and endopiriform nucleus (piriform network). Because these structures are prone to generate epileptic discharges, it seems critical to understand how they generate and regulate their physiological rhythmic activity. The piriform network gave rise to rhythmic spontaneous activity consisting of a succession of up and down states at an average frequency of 1.8 Hz, qualitatively similar to the corresponding neocortical activity. This activity originated in the deep layers of the piriform network, which displayed higher excitability and denser connectivity. A remarkable difference with neocortical activity was the speed of horizontal propagation (114 mm/s), one order of magnitude faster in the piriform network. Properties of the piriform cortex subserving fast horizontal propagation may underlie the higher vulnerability of this area to epileptic seizures.

PMID: 17925296 [PubMed - as supplied by publisher]

Neuromodulation by Glutamate and Acetylcholine can Change Circuit Dynamics by Regulating the Relative Influence of Afferent Input and Excitatory Feedback.

2007-10-26T10:21:00.001-07:00

Neuromodulation by Glutamate and Acetylcholine can Change Circuit Dynamics by Regulating the Relative Influence of Afferent Input and Excitatory Feedback.

Mol Neurobiol. 2007 Oct;36(2):184-200

Authors: Giocomo LM, Hasselmo ME

Substances such as acetylcholine and glutamate act as both neurotransmitters and neuromodulators. As neuromodulators, they change neural information processing by regulating synaptic transmitter release, altering baseline membrane potential and spiking activity, and modifying long-term synaptic plasticity. Slice physiology research has demonstrated that many neuromodulators differentially modulate afferent, incoming information compared to intrinsic and recurrent processing in cortical structures such as piriform cortex, neocortex, and the hippocampus. The enhancement of afferent (external) pathways versus the suppression at recurrent (internal) pathways could cause cortical dynamics to switch between a predominant influence of external stimulation to a predominant influence of internal recall. Modulation of afferent versus intrinsic processing could contribute to the role of neuromodulators in regulating attention, learning, and memory effects in behavior.

PMID: 17952661 [PubMed - in process]

The endocannabinoid system controls key epileptogenic circuits in the hippocampus.

2007-10-26T10:20:00.003-07:00

The endocannabinoid system controls key epileptogenic circuits in the hippocampus.

Neuron. 2006 Aug 17;51(4):455-66

Authors: Monory K, Massa F, Egertová M, Eder M, Blaudzun H, Westenbroek R, Kelsch W, Jacob W, Marsch R, Ekker M, Long J, Rubenstein JL, Goebbels S, Nave KA, During M, Klugmann M, Wölfel B, Dodt HU, Zieglgänsberger W, Wotjak CT, Mackie K, Elphick MR, Marsicano G, Lutz B

Balanced control of neuronal activity is central in maintaining function and viability of neuronal circuits. The endocannabinoid system tightly controls neuronal excitability. Here, we show that endocannabinoids directly target hippocampal glutamatergic neurons to provide protection against acute epileptiform seizures in mice. Functional CB1 cannabinoid receptors are present on glutamatergic terminals of the hippocampal formation, colocalizing with vesicular glutamate transporter 1 (VGluT1). Conditional deletion of the CB1 gene either in cortical glutamatergic neurons or in forebrain GABAergic neurons, as well as virally induced deletion of the CB1 gene in the hippocampus, demonstrate that the presence of CB1 receptors in glutamatergic hippocampal neurons is both necessary and sufficient to provide substantial endogenous protection against kainic acid (KA)-induced seizures. The direct endocannabinoid-mediated control of hippocampal glutamatergic neurotransmission may constitute a promising therapeutic target for the treatment of disorders associated with excessive excitatory neuronal activity.

PMID: 16908411 [PubMed - indexed for MEDLINE]

Cannabinoid CB1 receptor antagonists cause status epilepticus-like activity in the hippocampal neuronal culture model of acquired epilepsy.

2007-10-26T10:20:00.001-07:00

Cannabinoid CB1 receptor antagonists cause status epilepticus-like activity in the hippocampal neuronal culture model of acquired epilepsy.

Neurosci Lett. 2007 Jan 3;411(1):11-6

Authors: Deshpande LS, Sombati S, Blair RE, Carter DS, Martin BR, DeLorenzo RJ

Status epilepticus (SE) is a major medical emergency associated with a significant morbidity and mortality. Little is known about the mechanisms that terminate seizure activity and prevent the development of status epilepticus. Cannabinoids possess anticonvulsant properties and the endocannabinoid system has been implicated in regulating seizure duration and frequency. Endocannabinoids regulate synaptic transmission and dampen seizure activity via activation of the presynaptic cannabinoid receptor 1 (CB1). This study was initiated to evaluate the role of CB1 receptor-dependent endocannabinoid synaptic transmission towards preventing the development of status epilepticus-like activity in the well-characterized hippocampal neuronal culture model of acquired epilepsy using patch clamp electrophysiology. Application of the CB1 receptor antagonists SR141716A (1 microM) or AM251 (1 microM) to "epileptic" neurons caused the development of continuous epileptiform activity, resembling electrographic status epilepticus. The induction of status epilepticus-like activity by CB1 receptor antagonists was reversible and could be overcome by maximal concentrations of CB1 agonists. Similar treatment of control neurons with CB1 receptor antagonists did not produce status epilepticus or hyperexcitability. These findings suggest that CB1 receptor-dependent endocannabinoid endogenous tone plays an important role in modulating seizure frequency and duration and preventing the development of status epilepticus-like activity in populations of epileptic neurons. The regulation of seizure activity and prevention of status epilepticus by the endocannabinoid system offers an important insight into understanding the basic mechanisms that control the development of continuous epileptiform discharges.

PMID: 17110038 [PubMed - indexed for MEDLINE]

Potential therapeutical effects of cannabidiol in children with pharmacoresistant epilepsy.

2007-10-26T10:19:00.007-07:00

Potential therapeutical effects of cannabidiol in children with pharmacoresistant epilepsy.

Med Hypotheses. 2007;68(4):920-1

Authors: Cortesi M, Fusar-Poli P

PMID: 17112679 [PubMed - indexed for MEDLINE]

Endocannabinoids block status epilepticus in cultured hippocampal neurons.

2007-10-26T10:19:00.005-07:00

Endocannabinoids block status epilepticus in cultured hippocampal neurons.

Eur J Pharmacol. 2007 Mar 8;558(1-3):52-9

Authors: Deshpande LS, Blair RE, Ziobro JM, Sombati S, Martin BR, DeLorenzo RJ

Status epilepticus is a serious neurological disorder associated with a significant morbidity and mortality. Antiepileptic drugs such as diazepam, phenobarbital and phenytoin are the mainstay of status epilepticus treatment. However, over 20% of status epilepticus cases are refractory to the initial treatment with two or more antiepileptic drugs. Endocannabinoids have been implicated as playing an important role in regulating seizure activity and seizure termination. This study evaluated the effects of the major endocannabinoids methanandamide and 2-arachidonylglycerol (2-AG) on status epilepticus in the low-Mg(2+) hippocampal neuronal culture model. Status epilepticus in this model was resistant to treatment with phenobarbital and phenytoin. Methanandamide and 2-AG inhibited status epilepticus in a dose-dependent manner with an EC(50) of 145+/-4.15 nM and 1.68+/-0.19 microM, respectively. In addition, the anti-status epilepticus effects of methanandamide and 2-AG were mediated by activation of the cannabinoid CB(1) receptor since they were blocked by the cannabinoid CB(1) receptor antagonist AM251. These results provide the first evidence that the endocannabinoids, methanandamide and 2-AG, are effective inhibitors of refractory status epilepticus in the hippocampal neuronal culture model and indicate that regulating the endocannabinoid system may provide a novel therapeutic approach for treating refractory status epilepticus.

PMID: 17174949 [PubMed - indexed for MEDLINE]

Prevention of plasticity of endocannabinoid signaling inhibits persistent limbic hyperexcitability caused by developmental seizures.

2007-10-26T10:19:00.003-07:00

Prevention of plasticity of endocannabinoid signaling inhibits persistent limbic hyperexcitability caused by developmental seizures.

J Neurosci. 2007 Jan 3;27(1):46-58

Authors: Chen K, Neu A, Howard AL, Földy C, Echegoyen J, Hilgenberg L, Smith M, Mackie K, Soltesz I

Depolarization-induced suppression of inhibition (DSI) is an endocannabinoid-mediated short-term plasticity mechanism that couples postsynaptic Ca2+ rises to decreased presynaptic GABA release. Whether the gain of this retrograde synaptic mechanism is subject to long-term modulation by glutamatergic excitatory inputs is not known. Here, we demonstrate that activity-dependent long-term DSI potentiation takes place in hippocampal slices after tetanic stimulation of Schaffer collateral synapses. This activity-dependent, long-term plasticity of endocannabinoid signaling was specific to GABAergic synapses, as it occurred without increases in the depolarization-induced suppression of excitation. Induction of tetanus-induced DSI potentiation in vitro required a complex pathway involving AMPA/kainate and metabotropic glutamate receptor as well as CB1 receptor activation. Because DSI potentiation has been suggested to play a role in persistent limbic hyperexcitability after prolonged seizures in the developing brain, we used these mechanistic insights into activity-dependent DSI potentiation to test whether interference with the induction of DSI potentiation prevents seizure-induced long-term hyperexcitability. The results showed that the in vitro, tetanus-induced DSI potentiation was occluded by previous in vivo fever-induced (febrile) seizures, indicating a common pathway. Accordingly, application of CB1 receptor antagonists during febrile seizures in vivo blocked the seizure-induced persistent DSI potentiation, abolished the seizure-induced upregulation of CB1 receptors, and prevented the emergence of long-term limbic hyperexcitability. These results reveal a new form of activity-dependent, long-term plasticity of endocannabinoid signaling at perisomatic GABAergic synapses, and demonstrate that blocking the induction of this plasticity abolishes the long-term effects of prolonged febrile seizures in the developing brain.

PMID: 17202471 [PubMed - indexed for MEDLINE]

Development of pharmacoresistance to benzodiazepines but not cannabinoids in the hippocampal neuronal culture model of status epilepticus.

2007-10-26T10:19:00.001-07:00

Development of pharmacoresistance to benzodiazepines but not cannabinoids in the hippocampal neuronal culture model of status epilepticus.

Exp Neurol. 2007 Apr;204(2):705-13

Authors: Deshpande LS, Blair RE, Nagarkatti N, Sombati S, Martin BR, DeLorenzo RJ

Status epilepticus (SE) is a life-threatening neurological disorder associated with a significant morbidity and mortality. Benzodiazepines are the initial drugs of choice for the treatment of SE. Despite aggressive treatment, over 40% of SE cases are refractory to the initial treatment with two or more medications. It would be a major advance in the clinical management of SE to identify novel anticonvulsant agents that do not lose their ability to treat SE with increasing seizure duration. Cannabinoids have recently been demonstrated to regulate seizure activity in brain. However, it remains to be seen whether they develop pharmacoresistance upon prolonged SE. In this study, we used low Mg(2+) to induce SE in hippocampal neuronal cultures and in agreement with animal models and human SE confirm the development of resistance to benzodiazepine with increasing durations of SE. Thus, lorazepam (1 microM) was effective in blocking low Mg(2+) induced high-frequency spiking for up to 30 min into SE. However, by 1 h and 2 h of SE onset it was only 10-15% effective in suppressing SE. In contrast, the cannabinoid type-1 (CB1) receptor agonist, WIN 55,212-2 (1 microM) in a CB1 receptor-dependent manner completely abolished SE at all the time points tested even out to 2 h after SE onset, a condition where resistance developed to lorazepam. Thus, the use of cannabinoids in the treatment of SE may offer a unique approach to controlling SE without the development of pharmacoresistance observed with conventional treatments.

PMID: 17289026 [PubMed - indexed for MEDLINE]

On-demand activation of the endocannabinoid system in the control of neuronal excitability and epileptiform seizures.

2007-10-26T10:18:00.001-07:00

On-demand activation of the endocannabinoid system in the control of neuronal excitability and epileptiform seizures.

Biochem Pharmacol. 2004 Nov 1;68(9):1691-8

Authors: Lutz B

Neurons intensively exchange information among each other using both inhibitory and excitatory neurotransmitters. However, if the balance of excitation and inhibition is perturbed, the intensity of excitatory transmission may exceed a certain threshold and epileptic seizures can occur. As the occurrence of epilepsy in the human population is about 1%, the search for therapeutic targets to alleviate seizures is warranted. Extracts of Cannabis sativa have a long history in the treatment of various neurological diseases, including epilepsy. However, cannabinoids have been reported to exert both pro- and anti-convulsive activities. The recent progress in understanding the endogenous cannabinoid system has allowed new insights into these opposing effects of cannabinoids. When excessive neuronal activity occurs, endocannabinoids are generated on demand and activate cannabinoid type 1 (CB1) receptors. Using mice lacking CB1 receptors in principal forebrain neurons in a model of epileptiform seizures, it was shown that CB1 receptors expressed on excitatory glutamatergic neurons mediate the anti-convulsive activity of endocannabinoids. Systemic activation of CB1 receptors by exogenous cannabinoids, however, are anti- or pro-convulsive, depending on the seizure model used. The pro-convulsive activity of exogenous cannabinoids might be explained by the notion that CB1 receptors expressed on inhibitory GABAergic neurons are also activated, leading to a decreased release of GABA, and to a concomitant increase in seizure susceptibility. The concept that the endogenous cannabinoid system is activated on demand suggests that a promising strategy to alleviate seizure frequency is the enhancement of endocannabinoid levels by inhibiting the cellular uptake and the degradation of these endogenous compounds.

PMID: 15450934 [PubMed - indexed for MEDLINE]

Altering cannabinoid signaling during development disrupts neuronal activity.

2007-10-26T10:17:00.005-07:00

Altering cannabinoid signaling during development disrupts neuronal activity.

Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9388-93

Authors: Bernard C, Milh M, Morozov YM, Ben-Ari Y, Freund TF, Gozlan H

In adult cortical tissue, recruitment of GABAergic inhibition prevents the progression of synchronous population discharges to epileptic activity. However, at early developmental stages, GABA is excitatory and thus unable to fulfill this role. Here, we report that retrograde signaling involving endocannabinoids is responsible for the homeostatic control of synaptic transmission and the resulting network patterns in the immature hippocampus. Blockade of cannabinoid type 1 (CB1) receptor led to epileptic discharges, whereas overactivation of CB1 reduced network activity in vivo. Endocannabinoid signaling thus is able to keep population discharge patterns within a narrow physiological time window, balancing between epilepsy on one side and sparse activity on the other, which may result in impaired developmental plasticity. Disturbing this delicate balance during pregnancy in either direction, e.g., with marijuana as a CB1 agonist or with an antagonist marketed as an antiobesity drug, can have profound consequences for brain maturation even in human embryos.

PMID: 15964987 [PubMed - indexed for MEDLINE]

Alternative therapies for seizures: promises and dangers.

2007-10-26T10:17:00.003-07:00

Alternative therapies for seizures: promises and dangers.

Semin Neurol. 2007 Sep;27(4):325-30

Authors: Sirven JI

Complementary and alternative medicine (CAM) is increasingly being used for a multitude of medical problems, one of them being seizures. This article discusses the prevalence of CAM use for seizures and epilepsy. Evidence-based data regarding CAM for epilepsy are presented as well as potential safety concerns regarding ephedra and cannabis use.

PMID: 17701869 [PubMed - in process]

[Therapeutic use of cannabinoids in neurology]

2007-10-26T10:17:00.001-07:00

[Therapeutic use of cannabinoids in neurology]

Schmerz. 2003 Oct;17(5):367-73

Authors: Schwenkreis P, Tegenthoff M

This review gives insight into the potential therapeutical role of cannabinoids in neurology. Preclinical data are presented which could give a rationale for the clinical use of cannabinoids in the fields of multiple sclerosis, spasticity, epilepsy, movement disorders, and neuroprotection after traumatic head injury or ischemic stroke. Besides, clinical data (case reports, open-label and randomised controlled studies) dealing with the therapeutical use of cannabinoids in these fields are reported and discussed. At present, clinical data are insufficient to recommend the use of cannabinoids in any neurological disease as standard therapy. Several questions still have to be answered (which cannabinoid? which way of administration? stimulation of endogenous cannabinoids? separation between desired and undesired effects?), and controlled studies are still needed to clarify the potential therapeutical role of cannabinoids in neurology.

PMID: 14513344 [PubMed - indexed for MEDLINE]

Delta9-tetrahydrocannabinol and epilepsy in the photosensitive baboon, Papio papio.

2007-10-26T10:16:00.005-07:00

Delta9-tetrahydrocannabinol and epilepsy in the photosensitive baboon, Papio papio.

Epilepsia. 1974 Jun;15(2):255-64

Authors: Meldrum BS, Fariello RG, Puil EA, Derouaux M, Naquet R

PMID: 4525183 [PubMed - indexed for MEDLINE]

Anticonvulsant effects of cannabinoids in mice: drug interactions within cannabinoids and cannabinoid interactions with phenytoin.

2007-10-26T10:16:00.003-07:00

Anticonvulsant effects of cannabinoids in mice: drug interactions within cannabinoids and cannabinoid interactions with phenytoin.

Psychopharmacologia. 1974 Jul 11;37(3):255-64

Authors: Chesher GB, Jackson DM

PMID: 4850601 [PubMed - indexed for MEDLINE]

Letter: Cannabidiol and electroencephalographic epileptic activity.

2007-10-26T10:16:00.001-07:00

Letter: Cannabidiol and electroencephalographic epileptic activity.

JAMA. 1974 Dec 23-30;230(12):1635

Authors: Perez-Reyes M, Wingfield M

PMID: 4612180 [PubMed - indexed for MEDLINE]

The pharmacology of the cannabinoid system-a question of efficacy and selectivity.

2007-10-26T10:14:00.007-07:00

The pharmacology of the cannabinoid system-a question of efficacy and selectivity.

Mol Neurobiol. 2007 Aug;36(1):15-25

Authors: Fowler CJ

Our knowledge of the function of the cannabinoid system in the body has been aided by the availability of pharmacological agents that affect its function. This has been achieved by the design of agents that either directly interact with the receptor (agonists and antagonist/inverse agonists) and agents that indirectly modulate the receptor output by changing the levels of the endogenous cannabinoids (endocannabinoids). In this review, examples of the most commonly used receptor agonists, antagonists/inverse agonists, and indirectly acting agents (anandamide uptake inhibitors, fatty acid amide hydrolase inhibitors, monoacylglycerol lipase inhibitors) are given, with particular focus upon their selectivity and, in the case of the directly acting compounds, efficacy. Finally, the links between the endocannabinoid and cyclooxygenase pathways are explored, in particular, with respect to agents whose primary function is to inhibit cyclooxygenase activity, but which also interact with the endocannabinoid system.

PMID: 17952646 [PubMed - in process]

Cannabinoid CB(2) Receptor-Mediated Anti-nociception in Models of Acute and Chronic Pain.

2007-10-26T10:14:00.005-07:00

Cannabinoid CB(2) Receptor-Mediated Anti-nociception in Models of Acute and Chronic Pain.

Mol Neurobiol. 2007 Aug;36(1):26-35

Authors: Jhaveri MD, Sagar DR, Elmes SJ, Kendall DA, Chapman V

The endocannabinoid system consists of cannabinoid CB(1) and CB(2) receptors, endogenous ligands and their synthesising/metabolising enzymes. Cannabinoid receptors are present at key sites involved in the relay and modulation of nociceptive information. The analgesic effects of cannabinoids have been well documented. The usefulness of nonselective cannabinoid agonists can, however, be limited by psychoactive side effects associated with activation of CB(1) receptors. Following the recent evidence for CB(2) receptors existing in the nervous system and reports of their up-regulation in chronic pain states and neurodegenerative diseases, much research is now aimed at shedding light on the role of the CB(2) receptor in human disease. Recent studies have demonstrated anti-nociceptive effects of selective CB(2) receptor agonists in animal models of pain in the absence of CNS side effects. This review focuses on the analgesic potential of CB(2) receptor agonists for inflammatory, post-operative and neuropathic pain states and discusses their possible sites and mechanisms of action.

PMID: 17952647 [PubMed - in process]

Cannabinoids and gliomas.

2007-10-26T10:14:00.003-07:00

Cannabinoids and gliomas.

Mol Neurobiol. 2007 Aug;36(1):60-7

Authors: Velasco G, Carracedo A, Blázquez C, Lorente M, Aguado T, Haro A, Sánchez C, Galve-Roperh I, Guzmán M

Cannabinoids, the active components of Cannabis sativa L., act in the body by mimicking endogenous substances-the endocannabinoids-that activate specific cell surface receptors. Cannabinoids exert various palliative effects in cancer patients. In addition, cannabinoids inhibit the growth of different types of tumor cells, including glioma cells, in laboratory animals. They do so by modulating key cell signaling pathways, mostly the endoplasmic reticulum stress response, thereby inducing antitumoral actions such as the apoptotic death of tumor cells and the inhibition of tumor angiogenesis. Of interest, cannabinoids seem to be selective antitumoral compounds, as they kill glioma cells, but not their non-transformed astroglial counterparts. On the basis of these preclinical findings, a pilot clinical study of Delta(9)-tetrahydrocannabinol (THC) in patients with recurrent glioblastoma multiforme has been recently run. The good safety profile of THC, together with its possible growth-inhibiting action on tumor cells, justifies the setting up of future trials aimed at evaluating the potential antitumoral activity of cannabinoids.

PMID: 17952650 [PubMed - in process]

The endocannabinoid system and Alzheimer's disease.

2007-10-26T10:14:00.001-07:00

The endocannabinoid system and Alzheimer's disease.

Mol Neurobiol. 2007 Aug;36(1):75-81

Authors: Benito C, Núñez E, Pazos MR, Tolón RM, Romero J

The importance of the role of the endocannabinoid system (ECS) in neurodegenerative diseases has grown during the past few years. Mostly because of the high density and wide distribution of cannabinoid receptors of the CB(1) type in the central nervous system (CNS), much research focused on the function(s) that these receptors might play in pathophysiological conditions. Our current understanding, however, points to much diverse roles for this system. In particular, other elements of the ECS, such as the fatty acid amide hydrolase (FAAH) or the CB(2) cannabinoid receptor are now considered as promising pharmacological targets for some diseases and new cannabinoids have been incorporated as therapeutic tools. Although still preliminary, recent reports suggest that the modulation of the ECS may constitute a novel approach for the treatment of Alzheimer's disease (AD). Data obtained in vitro, as well as in animal models for this disease and in human samples seem to corroborate the notion that the activation of the ECS, through the use of agonists or by enhancing the endogenous cannabinoid tone, may induce beneficial effects on the evolution of this disease.

PMID: 17952652 [PubMed - in process]

Cannabinoids in eating disorders and obesity.

2007-10-26T10:13:00.005-07:00

Cannabinoids in eating disorders and obesity.

Mol Neurobiol. 2007 Aug;36(1):113-28

Authors: Arias Horcajadas F

Cannabinoid system is a crucial mechanism in regulating food intake and energy metabolism. It is involved in central and peripheral mechanisms regulating such behavior, interacting with many other signaling systems with a role in metabolic regulation. Cannabinoid agonists promote food intake, and soon a cannabinoid antagonist, rimonabant, will be marketed for the treatment of obesity. It not only causes weight loss, but also alleviates metabolic syndrome. We present a review of current knowledge on this subject, along with data from our own research: genetic studies on this system in eating disorders and obesity and studies locating cannabinoid receptors in areas related to food intake. Such studies suggest cannabinoid hyperactivity in obesity, and this excessive activity may have prognostic implications.

PMID: 17952656 [PubMed - in process]

Cannabinoid-based medicines for neurological disorders-clinical evidence.

2007-10-26T10:13:00.003-07:00

Cannabinoid-based medicines for neurological disorders-clinical evidence.

Mol Neurobiol. 2007 Aug;36(1):129-36

Authors: Wright S

Whereas the cannabis plant has a long history of medicinal use, it is only in recent years that a sufficient understanding of the pharmacology of the main plant constituents has allowed for a better understanding of the most rational therapeutic targets. The distribution of cannabinoid receptors, both within the nervous system and without, and the development of pharmacological tools to investigate their function has lead to a substantial increase in efforts to develop cannabinoids as therapeutic agents. Concomitant with these efforts, the understanding of the pharmacology of plant cannabinoids at receptor and other systems distinct from the cannabinoid receptors suggests that the therapeutic applications of plant-derived cannabinoids (and presumably their synthetic derivatives also) may be diverse. This review aims to discuss the clinical evidence investigating the use of medicines derived, directly or indirectly, from plant cannabinoids with special reference to neurological disorders. Published studies suggest that the oral administration of cannabinoids may not be the preferred route of administration and that plant extracts show greater evidence of efficacy than synthetic compounds. One of these, Sativex(R) (GW Pharmaceuticals), was approved as a prescription medicine in Canada in 2005 and is currently under regulatory review in the EU.

PMID: 17952657 [PubMed - in process]

Functional blockage of the cannabinoid receptor type 1 evokes a kappa-opiate-dependent analgesia.

2007-10-26T10:13:00.001-07:00

Functional blockage of the cannabinoid receptor type 1 evokes a kappa-opiate-dependent analgesia.

J Neurochem. 2007 Oct 22;

Authors: Sáez-Cassanelli JL, Fontanella GH, Delgado-García JM, Carrión AM

Progress in the control and treatment of pain may be facilitated by a better understanding of mechanisms underlying nociceptive processing. Cannabinoids and opioids are endogenous modulator of pain sensation, but therapies based in these compounds are not completely exploited because of their side effects. To test the role of cannabinoid receptor type 1 (CB1-R) inhibition in nociception, we performed a subchronic administration of the CB1-R antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM281) in mice. This treatment provoked analgesia in peripheral thermal and visceral models of pain. Analysis of genes encoded for the opioid system in the spinal cord showed an increase in the expression of genes encoded for the kappa-opioid system in AM281-injected mice compared with vehicle-injected ones. Furthermore, systemic administration of nor-binaltorphimine, a kappa-opioid receptor antagonist, blocked AM281-induced analgesia. Finally, c-fos expression in the dorsal spinal cord and higher centers of pain processing after noxious stimulation were significantly lower in AM281-injected mice than in vehicle-injected animals, indicating that dynorphin could block nociceptive information transmission at the spinal cord level. These results indicate the existence of a cross-talk between opioid and cannabinoid systems in nociception. Furthermore, the results suggest that CB1-R antagonists could be useful as a new therapeutic approach for pain relief.

PMID: 17953671 [PubMed - as supplied by publisher]

Expression and Function of CB(1) Receptor in the Rat Striatum: Localization and Effects on D(1) and D(2) Dopamine Receptor-Mediated Motor Behaviors.

2007-10-26T10:12:00.005-07:00

Expression and Function of CB(1) Receptor in the Rat Striatum: Localization and Effects on D(1) and D(2) Dopamine Receptor-Mediated Motor Behaviors.

Neuropsychopharmacology. 2007 Oct 24;

Authors: Martín AB, Fernandez-Espejo E, Ferrer B, Gorriti MA, Bilbao A, Navarro M, Rodriguez de Fonseca F, Moratalla R

Cannabinoid CB(1) receptors are densely expressed on striatal projection neurons expressing dopamine D(1) or D(2) receptors. However, the specific neuronal distribution of CB(1) receptors within the striatum is not known. Previous research has established that the endocannabinoid system controls facilitation of behavior by dopamine D(2) receptors, but it is not clear if endocannabinoids also modulate D(1) receptor-mediated motor behavior. In the present study, we show that cannabinoid CB(1) receptor mRNA is present in striatonigral neurons expressing substance P and dopamine D(1) receptors, as well as in striatopallidal neurons expressing enkephalin and dopamine D(2) receptors. We explored the functional relevance of the interaction between dopamine D(1) and D(2) receptors and cannabinoid CB(1) receptors with behavioral pharmacology experiments. Potentiation of endogenous cannabinoid signaling by the uptake blocker AM404 blocked dopamine D(1) receptor-mediated grooming and D(2) receptor-mediated oral stereotypies. In addition, contralateral turning induced by unilateral intrastriatal infusion of D(1) receptor agonists is counteracted by AM404 and potentiated by the cannabinoid antagonist SR141716A. These results indicate that the endocannabinoid system negatively modulates D(1) receptor-mediated behaviors in addition to its previously described effect on dopamine D(2) receptor-mediated behaviors. The effect of AM404 on grooming behavior was absent in dopamine D(1) receptor knockout mice, demonstrating its dependence on D(1) receptors. This study indicates that the endocannabinoid system is a relevant negative modulator of both dopamine D(1) and D(2) receptor-mediated behaviors, a finding that may contribute to our understanding of basal ganglia motor disorders.Neuropsychopharmacology advance online publication, 24 October 2007; doi:10.1038/sj.npp.1301558.

PMID: 17957223 [PubMed - as supplied by publisher]

A neutral CB1 receptor antagonist reduces weight gain in rat.

2007-10-26T10:12:00.003-07:00

A neutral CB1 receptor antagonist reduces weight gain in rat.

Am J Physiol Regul Integr Comp Physiol. 2007 Oct 24;

Authors: Chambers AP, Vemuri VK, Peng Y, Wood JT, Olzewska T, Pittman QJ, Makriyannis A, Sharkey KA

Cannabinoid (CB) 1 receptor inverse agonists inhibit food intake in animals and humans, but also potentiate emesis. It is not clear whether these effects result from inverse agonist properties or from the blockade of endogenous cannabinoid signaling. Here, we examine the effect of a neutral CB1 antagonist, AM4113, on food intake, weight gain and emesis. Neutral antagonist and binding properties were confirmed in HEK293 cells transfected with human CB1 or CB2 receptors. AM4113 had no effect on forskolin stimulated cAMP production at concentrations up to 630 nM. The Ki value of AM4113 (0.80+/-0.44nM) in competitive binding assays with the CB1/2 agonist [(3)H]CP55,940 was 100-fold more selective for CB1 over CB2 receptors. We determined that AM4113 antagonized CB1 receptors in brain by blocking hypothermia induced by CP55,940. AM4113 (0-20 mg kg(-1)) significantly reduced food intake and weight gain in rat. Compared with AM251, higher doses of AM4113 were needed to produce similar effects on food intake and body weight. Unlike AM251 (5 mg kg(-1)), a highly anorectic dose of AM4113 (10 mg kg(-1)) did not significantly potentiate vomiting induced by the emetic morphine-6-glucoronide. We show that a centrally active neutral CB1 receptor antagonist shares the appetite suppressant and weight loss effects of inverse agonists. If these compounds display similar properties in humans they could be developed into a new class of anti-obesity agents. Key words: Cannabinoid receptor, Food intake, inverse agonist, obesity, emesis.

PMID: 17959701 [PubMed - as supplied by publisher]

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