Discriminative stimulus properties of stereoisomers of cyclazocine in phencyclidine-trained squirrel monkeys.
Squirrel monkeys were trained to discriminate 0.16 mg/kg phencyclidine (PCP) from saline in a two-layer drug discrimination task on a fixed-ratio 32 schedule of food presentation. After reliable discriminative control of lever choice was established, dose-response determinations for generalization to the training dose of PCP were made with several doses of PCP, a racemic mixture of cyclazocine and the pure (+)- and (-)-isomers of cyclazocine. Only PCP and the (+)-isomer produced dose-dependent PCP-appropriate responding. Neither the racemic mixture nor (-)-cyclazocine produced over 25% PCP-appropriate responding at any of the doses tested. (+)-Cyclazocine was eight times less potent than PCP in producing drug-lever appropriate responding. (-)-Cyclazocine was about 30 times more potent than PCP and over 200 times more potent than (+)-cyclazocine in overall response rate suppression. The potency of the racemic mixture for response-rate suppression was consistent with an additive effect of the isomers. Neither the PCP-lever appropriate responding produced by (+)-cyclazocine nor the response-rate suppression produced by (-)-cyclazocine were antagonized by naloxone. Thus, racemic cyclazocine is composed of two isomers with differing behavioral effects. The (-)-isomer is more potent, and the (+)-isomer has more specificity for PCP-like effects.
D000818:Animals; D001665:Binding Sites; D003216:Conditioning, Operant / Q000187:drug effects; D003496:Cyclazocine / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects; D012453:Saimiri; D013237:Stereoisomerism
D011957:Receptors, Opioid; D009270:Naloxone; D010622:Phencyclidine; D003496:Cyclazocine