Evaluation of the reinforcing effects of the cannabinoid CB1 receptor antagonist, SR141716, in rhesus monkeys.
The abuse liability of a selective cannabinoid CB1 receptor antagonist, SR141716 (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxyamide hydrochloride), was evaluated in rhesus monkeys. Four rhesus monkeys with chronically indwelling venous catheters were initially trained to self-administer cocaine (30 microg/kg/injection) during daily 1-h sessions under a fixed ratio 50 (FR50) schedule of reinforcement. SR141716 was subsequently substituted for cocaine, and SR141716 dose was varied from 1 to 100 microg/kg/injection. Each dose of SR141716 was tested for four consecutive sessions and each unit dose was separated by at least three sessions of cocaine self-administration. Substitution of SR141716 for cocaine resulted in rapid extinction of lever pressing and none of the doses of SR141716 tested was self-administered above the vehicle levels. When the highest dose of SR141716 (100 microg/kg/injection) was evaluated, self-administration behavior was suppressed below vehicle levels suggesting that behaviorally active doses were evaluated. Since positive results in self-administration tests are generally predictive of abuse potential, the negative results with SR141716 suggest that this drug would likely have low abuse liability.
Beardsley
Patrick M
PM
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, 410 North 12th Street, Smith Building #756A, Richmond, VA 23298-0613, USA. pbeardsl@hsc.vcu.edu
Dance
Mario E
ME
Balster
Robert L
RL
Munzar
Patrik
P
D000818:Animals; D002186:Cannabinoids / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D019970:Cocaine-Related Disorders; D004305:Dose-Response Relationship, Drug; D008253:Macaca mulatta; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012055:Reinforcement Schedule; D000077285:Rimonabant; D012646:Self Administration
D002186:Cannabinoids; D000697:Central Nervous System Stimulants; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D003042:Cocaine; D000077285:Rimonabant