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A comparison of the discriminative stimulus properties of delta 9- tetrahydrocannabinol and CP 55,940 in rats and rhesus monkeys

LH Gold, RL Balster, RL Barrett, DT Britt and BR Martin

Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond.

CP 55,940 [(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4- (3- hydroxypropyl)cyclohexanol] is a potent bicyclic analog of delta 9- tetrahydrocannabinol (THC) which has been used as a probe for a cannabinoid recognition site in neural tissue. In the present study, CP 55,490 was evaluated for delta 9-THC-like effects in rats and rhesus monkeys trained to discriminate delta 9-THC from vehicle. Rats trained to discriminate delta 9-THC (3.0 mg/kg i.p.) from vehicle were tested with various doses of delta 9-THC and CP 55,940 at both 30 and 90 min postinjection. Catalepsy was measured immediately after these operant tests using an adaptation of the mouse ring-test. In rats, CP 55,940 substituted for delta 9-THC at both 30 and 90 min postinjection at a dose of 0.1 mg/kg that had minimal effects on rates of responding. Doses of delta 9-THC (greater than 3.0 mg/kg) and CP 55,940 (greater than 0.1 mg/kg) that reduced response rates by greater than 50% also produced substantial increases in catalepsy. CP 55,940 and delta 9-THC had a similar time course for discriminative stimulus effects, but CP 55,940 was about 30 times more potent. In monkeys, the training dose of delta 9-THC ranged from 0.04 to 0.16 mg/kg i.m., adjusted individually to minimize response-rate disruption. After training, monkeys were tested with various doses of delta 9-THC and CP 55,940 at 30 min postinjection.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 262, Issue 2, pp. 479-486, 08/01/1992
Copyright © 1992 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1992 by the American Society for Pharmacology and Experimental Therapeutics.