Effects of the cannabinoid CB(1) receptor antagonist, SR141716A, after Delta(9)-tetrahydrocannabinol withdrawal.
Rats were trained to lever press according to variable interval 10 s schedules during daily experimental sessions composed of six 3 min food reinforcement periods and were treated twice daily for 6 days with either vehicle or escalating regimens of Delta(9)-tetrahydrocannabinol. On days 7 and 8, the rats were challenged with vehicle and cumulative doses of SR141716A (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4, -dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxyamide hydrochloride), a cannabinoid CB(1) receptor antagonist, up to 3 and 9 mg/kg, respectively. Response rates increased during Delta(9)-tetrahydrocannabinol withdrawal and towards those of the vehicle treatment group suggesting a waning of the direct effects of Delta(9)-tetrahydrocannabinol. SR141716A reduced response rates but only in rats pre-treated with Delta(9)-tetrahydrocannabinol. These data suggest that dependence upon Delta(9)-tetrahydrocannabinol was induced and SR141716A precipitated withdrawal.
Beardsley
P M
PM
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Box 980613, 410 N. 12th Street, Smith Building #756A, Richmond, VA 23298-0613, USA.
Martin
B R
BR
D000818:Animals; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D011619:Psychotropic Drugs / Q000009:adverse effects*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors*; D000077285:Rimonabant; D013375:Substance Withdrawal Syndrome / Q000209:etiology* / Q000517:prevention & control; D019966:Substance-Related Disorders / Q000209:etiology / Q000517:prevention & control
D010880:Piperidines; D011619:Psychotropic Drugs; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D013759:Dronabinol; D000077285:Rimonabant