Expression and Function of CB1 Receptor in the Rat Striatum: Localization and Effects on D1 and D2 Dopamine Receptor-Mediated Motor Behaviors
| Autor: | Fernando Rodríguez de Fonseca, Ana B. Martín, Emilio Fernández-Espejo, Rosario Moratalla, Belen Ferrer, Miguel Navarro, Ainhoa Bilbao, Miguel Angel Gorriti |
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| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Movement Nerve Tissue Proteins D1-like receptor Arachidonic Acids Motor Activity Substance P Depolarization-induced suppression of inhibition Models Biological Rats Sprague-Dawley Dopamine receptor D1 Piperidines Receptor Cannabinoid CB1 Dopamine receptor D3 Internal medicine Dopamine receptor D2 medicine Animals Neurons Pharmacology Behavior Animal Receptors Dopamine D2 Chemistry Receptors Dopamine D1 Dopaminergic Enkephalins Grooming Corpus Striatum Rats Psychiatry and Mental health Endocrinology Gene Expression Regulation nervous system D2-like receptor Dopamine receptor Dopamine Agonists Pyrazoles lipids (amino acids peptides and proteins) 2 3 4 5-Tetrahydro-7 8-dihydroxy-1-phenyl-1H-3-benzazepine Rimonabant Neuroscience |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1740-634X 0893-133X |
| DOI: | 10.1038/sj.npp.1301558 |
| Popis: | 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 D 2 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 CB 1 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. © 2008 Nature Publishing Group All rights reserved. |
| Databáze: | OpenAIRE |
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