Effects of cannabinoid receptor stimulation and blockade on catalepsy produced by dopamine receptor antagonists.
The ability of cannabinoid receptor stimulation or blockade to alter catalepsy produced by dopamine D1 and D2 receptor antagonists was studied in rats. The cannabinoid receptor antagonist SR 141716A (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1H- pyrazole-3-carboxamidehydrochloride) (0.5 and 2.5 mg/kg) reduced catalepsy elicited by the cannabinoid receptor agonist CP 55,940 (1 alpha,2-(R)-5-(1,1-dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl ) cyclohexyl-phenol) (0.5 mg/kg). However, SR 141716A (0.5 and 2.5 mg/kg) did not decrease catalepsy produced by the dopamine D1 receptor antagonist SCH 23390 (R-(+)-7chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5- tetrahydro-1-H-3-benzazepine) (0.5 mg/kg) or the dopamine D2 receptor antagonist raclopride (S(-)-3,5-dichloro-N-(1-ethyl-2-pyrrolidinyl)-methyl-6-methoxysalicylami de) (2.5 mg/kg), suggesting that, under these conditions, endogenous cannabinoid ligands do not modulate the cataleptic effects of dopamine D1 or D2 receptor antagonists. In contrast, CP 55,940 (0.025 and 0.1 mg/kg), at doses which do not produce catalepsy when administered alone, enhanced catalepsy produced by SCH 23390 and raclopride. These results suggest that stimulation, but not blockade, of brain cannabinoid receptors modifies catalepsy behavior produced by selective dopamine D1 and D2 receptor blockade.
Anderson
J J
JJ
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Kask
A M
AM
Chase
T N
TN
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects*; D002375:Catalepsy / Q000145:classification*; D003511:Cyclohexanols / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D020891:Raclopride; D051381:Rats; D017207:Rats, Sprague-Dawley; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000187:drug effects*; D000077285:Rimonabant; D012457:Salicylamides / Q000494:pharmacology
D001552:Benzazepines; D003511:Cyclohexanols; D018492:Dopamine Antagonists; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D012457:Salicylamides; D020891:Raclopride; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D000077285:Rimonabant