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

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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.

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.

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.

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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.

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.

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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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