title: Expression and function of CB1 receptor in the rat striatum: localization and effects on D1 and D2 dopamine receptor-mediated motor behaviors.
abstract: Cannabinoid CB1 receptors are densely expressed on striatal projection neurons expressing dopamine D1 or D2 receptors. However, the specific neuronal distribution of CB1 receptors within the striatum is not known. Previous research has established that the endocannabinoid system controls facilitation of behavior by dopamine D2 receptors, but it is not clear if endocannabinoids also modulate D1 receptor-mediated motor behavior. In the present study, we show that cannabinoid CB1 receptor mRNA is present in striatonigral neurons expressing substance P and dopamine D1 receptors, as well as in striatopallidal neurons expressing enkephalin and dopamine D2 receptors. We explored the functional relevance of the interaction between dopamine D1 and D2 receptors and cannabinoid CB1 receptors with behavioral pharmacology experiments. Potentiation of endogenous cannabinoid signaling by the uptake blocker AM404 blocked dopamine D1 receptor-mediated grooming and D2 receptor-mediated oral stereotypies. In addition, contralateral turning induced by unilateral intrastriatal infusion of D1 receptor agonists is counteracted by AM404 and potentiated by the cannabinoid antagonist SR141716A. These results indicate that the endocannabinoid system negatively modulates D1 receptor-mediated behaviors in addition to its previously described effect on dopamine D2 receptor-mediated behaviors. The effect of AM404 on grooming behavior was absent in dopamine D1 receptor knockout mice, demonstrating its dependence on D1 receptors. This study indicates that the endocannabinoid system is a relevant negative modulator of both dopamine D1 and D2 receptor-mediated behaviors, a finding that may contribute to our understanding of basal ganglia motor disorders.
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
authors.forename: Ana Belén
authors.initials: AB
authors.lastname: Martín
authors.forename: Emilio
authors.initials: E
authors.lastname: Fernandez-Espejo
authors.forename: Belén
authors.initials: B
authors.lastname: Ferrer
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Gorriti
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Bilbao
authors.forename: Miguel
authors.initials: M
authors.lastname: Navarro
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodriguez de Fonseca
authors.forename: Rosario
authors.initials: R
authors.lastname: Moratalla
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006120:Grooming / Q000187:drug effects / Q000502:physiology; D008297:Male; D008954:Models, Biological; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009068:Movement / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000145:classification / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D000077285:Rimonabant; D013373:Substance P / Q000235:genetics / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D018491:Dopamine Agonists; D004745:Enkephalins; D009419:Nerve Tissue Proteins; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013373:Substance P; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000077285:Rimonabant; C107594:N-(4-hydroxyphenyl)arachidonylamide