Phencyclidine-like discriminative stimulus effects of the stereoisomers of alpha- and beta-cyclazocine in rats.
Stereoisomers of alpha- and beta-cyclazocine were tested in rats trained to discriminate phencyclidine (PCP; 3.0 mg/kg i.p.) from saline in a two-lever, food-reinforced, drug-discrimination procedure. (+)-Alpha-cyclazocine and both (+)- and (-)-beta-cyclazocine substituted for PCP. Neither (+/-) nor (-)-alpha-cyclazocine substituted for PCP, although both compounds had potent, response-rate decreasing effects. When these two drugs were tested in combination with naltrexone, rate-suppressing effects were somewhat attenuated and both then resulted in substantial PCP-lever responding. Thus, PCP-like effects in the alpha series can be masked by opiate effects. (-)-Beta-cyclazocine was the most potent compound for mimicking the PCP discriminative stimulus, being 4 to 5 times more potent than PCP itself. The (+)-isomers in both the alpha and beta series were equipotent and over 10 times less potent than PCP. Thus, both stereoisomers of beta-cyclazocine have PCP-like discriminative stimulus properties and the (-)-isomer, in particular, is a very potent, selective, PCP-like compound. The stereoisomers of beta-cyclazocine have over a 50-fold potency difference for PCP-like effects, evidencing greater stereoselectivity for these actions than is commonly obtained with 6,7-benzomorphans. The stereoisomers of beta-cyclazocine should prove to be useful tools for studying the PCP/sigma-like effects of opioids.
Slifer
B L
BL
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond.
Balster
R L
RL
D000818:Animals; D003496:Cyclazocine / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005795:Generalization, Stimulus / Q000187:drug effects*; D008297:Male; D009271:Naltrexone / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
D009271:Naltrexone; D010622:Phencyclidine; D003496:Cyclazocine