Differential effects of σ and phencyclidine receptor ligands on learning

Abstract

Several phencyclidine (PCP) and σ receptor ligands were examined for their effects on a single trial passive avoidance test in rats. Rats were administered the PCP receptor ligands (+)-5-methyl-10,11-dihydro-5Hdibenzo[1,d]cyclohepten-5,10-imine maleate (MK-801), PCP, ketamine or the σ receptor ligands (+)-N-allylnormetazocine ((+)-NANM), (+)-pentazocine, (+)-3-hydroxyphenyl)-N-n-propylpiperidine ((+)-3-PPP) or 1,3-Di(2-[5- 3H]tolyl)guanidine (DTG) subcutaneously prior to acquisition of the passive avoidance response, and tested 24 h later for retention. MK-801 (0.1–0.3 mg/kg), PCP (0.54–1.7 mg/kg), ketamine (10.0–17.2 mg/kg) and (+)-N-allylnormetazocine (5.4–10.0 mg/kg) produced significant memory deficits. (+)-Pentazocine (54 mg/kg) and (+)-PPP (30 mg/kg) also produced retention deficits, but at significantly higher doses. DTG (0.3–3.0 mg/kg s.c.) had no effect on retention. There was a positive correlation between production of retention deficits and the compounds' PCP receptor binding affinity. The results suggest that the σ receptor is not involved in learning the passive avoidance response.