Evidence for multiple opiate receptor involvement in different phencyclidine-induced unconditioned behaviors in rats

Rats were used for comparing the behavioral response profiles of phencyclidine (PCP) and d,1-N-allylnormetazocine (NANM), two drugs that are proposed to exert their effects through the "PCP/sigma" receptor. Phencyclidine (1.0-5.0 mg/kg) and NANM (2.5-10.0 mg/kg) induced dose-related increases in locomotion, sniffing, repetitive head movements, non-object directed mouth movements, and ataxia. Both drugs also increased food and water consumption during the latter portion of the drug response. Ingestive behaviors induced by PCP (2.5 mg/kg), as with eating and drinking stimulated by the mu-opiate morphine (2.0 mg/kg), were blocked by a relatively low dose of the opiate antagonist naloxone (0.5 mg/kg). Multiple injections of PCP (2.5 mg/kg for 4 days) or NANM (10.0 mg/kg for 4 days) augmented several measures of behavioral activation, including horizontal locomotion, rearing, and nonfocused sniffing, but did not significantly change stereotyped behaviors or ataxia. Reciprocal cross-sensitization of locomotor activation is indicated by the finding that the response to a challenge injection of PCP (2.5 mg/kg) or to NANM (10.0 mg/kg) after 4 days of treatment with the other drug closely resembled the enhanced locomotor response observed after the chronic treatment. Phencyclidine and NANM thus appear to exert many of their effects on unconditioned behavior through common mechanisms, including interaction with sigma receptors. In addition, these findings are consistent with previous suggestions that a mu-opiate receptor system may modulate some effects of PCP.