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.

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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]