Pharmacological analysis of the phencyclidine-like discriminative stimulus properties of narcotic derivatives in rats.

The purpose of the present experiments was to evaluate the phencyclidine (PCP)-like discriminative stimulus properties of narcotic derivatives in the rat. Rats were trained to discriminate between saline and 3.0 mg/kg of PCP in a two-choice, shock-avoidance procedure. PCP-like stimulus control of behavior was produced by (in order of relative molar potency): l-cyclazocine greater than PCP greater than dl-cyclazocine greater than SKF 10,047 greater than MeO-cyclazocine greater than dextrorphan greater than d-cyclazocine. Metazocine and levalorphan also occasioned appreciable percentages of PCP-appropriate responding. Ten other narcotic derivatives, including pentazocine and nalorphine, occasioned only saline-appropriate responding. Among enantiomeric pairs, levocyclazocine was more potent than dextrocyclazocine, and dextrorphan but not levorphanol produced PCP-like discriminative effects. The specific narcotic antagonist naloxone failed to antagonize these PCP-like effects but rather increased the relative potency of cyclazocine and "unmasked" PCP-like effects of higher doses of metazocine. These results demonstrate that PCP and selected narcotic derivatives have similar components of action which appear to be mediated by sigma receptors rather than receptors which subserve the characteristic opioid actions of narcotic analgesics.