Discriminative stimulus effects of the PCP/sigma-ligand (+)-N-allylnormetazocine in monkeys.
(+)-N-Allylnormetazocine [(+)-NANM] binds to both the phencyclidine (PCP) receptor and the sigma-site in brain, with some selectivity for the latter. In rats, the discriminative stimulus effects of (+)-NANM are primarily PCP like. The present study was performed to determine if the discriminative effects of (+)-NANM in a primate species might reflect the actions of this drug at the sigma-site. Six squirrel monkeys were trained to discriminate between IM injections of saline and 1.0 mg/kg (+)-NANM in a two-choice discrete-trial avoidance procedure. In tests of stimulus generalization, dose-dependent increases in trials completed on the (+)-NANM choice lever were produced by (+)- and (-)-NANM, by PCP and the PCP-like drugs MK-801 and thienylcyclohexyl-piperidine, and by the opioids (+)- and (-)-cyclazocine and dextrorphan; order of potency correlated with reported affinities for the PCP receptor. High-affinity sigma-ligands, (+)-pentazocine, 1,3-di-ortho-tolylguanidine (DTG), haloperidol, and BMY 14802, as well as agonists at mu- and kappa-opioid receptors, occasioned selection of the saline-appropriate choice lever. Selection of the (+)-NANM choice lever was reduced by up to 35-50% when 1.0 mg/kg (+)-NANM was given concurrently with haloperidol or BMY 14802, but was not affected substantially by (-)-butaclamol, another sigma-ligand, or by naltrexone, an opioid antagonist. The discriminative effects of (+)-NANM in squirrel monkeys appear to be mediated largely by the PCP receptor and not by the sigma-site or opioid receptors.
Holtzman
S G
SG
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322.
D000818:Animals; D004193:Discrimination Learning / Q000187:drug effects*; D005795:Generalization, Stimulus / Q000187:drug effects*; D008024:Ligands; D008297:Male; D009271:Naltrexone / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D017478:Receptors, Phencyclidine / Q000378:metabolism*; D017480:Receptors, sigma / Q000378:metabolism*; D012453:Saimiri
D008024:Ligands; D009294:Narcotics; D017478:Receptors, Phencyclidine; D017480:Receptors, sigma; D009271:Naltrexone; C012134:SK&F 10047; D010620:Phenazocine