Intrastriatal injection of cannabinoid receptor agonists induced turning behavior in mice.
When injected unilaterally into the mouse striatum, cannabinoid agonists such as Win 55212-2 (1-100 ng/mouse), CP 55940 (0.1-50 ng/mouse), and anandamide (0.5-50 ng/mouse), the putative endogenous ligand of CB1 receptor, dose-dependently induced turning behavior. SR 141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1H- pyrazole-3-carboxamide hydrochloride], the selective antagonist of CB1 receptor, antagonized the three cannabinoid receptor agonists-induced turning with similar ED50s (0.13-0.15 mg/kg, IP). Spiroperidol (a D2 receptor blocker), (+)-SCH 23390 (a D1 receptor blocker), or prior 6-OHDA lesions of the striatum blocked Win 55212-2- and CP 55940-induced turning, thus suggesting the involvement of DA transmission in cannabinoid-induced turning. Taken together, these findings reinforce the notion of a cannabinoid receptor-mediated control of nigrostriatal function.
Souilhac
J
J
Neuropsychiatry Department, Sanofi Recherche, Montpellier, France.
Poncelet
M
M
Rinaldi-Carmona
M
M
Le Fur
G
G
Soubrié
P
P
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D048588:Benzoxazines; D002188:Cannabis / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism / Q000502:physiology*; D003511:Cyclohexanols / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007267:Injections; D051379:Mice; D009025:Morpholines / Q000008:administration & dosage / Q000494:pharmacology; D009281:Naphthalenes / Q000008:administration & dosage / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D016627:Oxidopamine / Q000633:toxicity; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D000077285:Rimonabant; D013237:Stereoisomerism; D013239:Stereotyped Behavior / Q000187:drug effects*
D000700:Analgesics; D048588:Benzoxazines; D003511:Cyclohexanols; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D018041:Receptors, Neurokinin-2; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D016627:Oxidopamine; D000077285:Rimonabant