Discriminative stimulus effects of the PCP/σ-ligand (+)- N-Allylnormetazocine in monkeys

Abstract

(+)- N-Allylnormetazocine [(+)-NANM] binds to both the phencyclidine (PCP) receptor and the σ-site in brain, with some selectivity for the latter. In rats, 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 σ-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 σ-ligands, (+)-pentazocine, 1,3-di- ortho-tolylguanidine (DTG), haloperidol, and BMY 14802, as well as agonists at μ- and κ-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 σ-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 σ-site or opioid receptors.