A comparison of the discriminative stimulus properties of delta 9-tetrahydrocannabinol and CP 55,940 in rats and rhesus monkeys.
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)
Gold
L H
LH
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond.
Balster
R L
RL
Barrett
R L
RL
Britt
D T
DT
Martin
B R
BR
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003511:Cyclohexanols / Q000378:metabolism / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000700:Analgesics; D003511:Cyclohexanols; D013759:Dronabinol; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol