Is the discriminative stimulus produced by phencyclidine due to an interaction with N-methyl-D-aspartate receptors?

Abstract

Rats were trained to discriminate phencyclidine (PCP) from saline at doses of 2 and 4 mg/kg, using a two-lever food reinforced operant technique. +/- N-allylnormetazocine (+/- SKF 10047), +5-methyl-10,11-dihydro-5H-dibenzo[A,D]cyclohepten-5,10-imine MK 801), 3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid (CPP) and ifenprodil, which have been shown to antagonise the effects of N-methyl-D-aspartate (NMDA), were tested for their ability to give rise to PCP-appropriate responding. In rats trained at both doses of PCP, +/- SKF 10047 (2-12 mg/kg) and MK 801 (0.0125-0.2 mg/kg) produced dose-related responding on the lever associated with PCP injection. The relative potency of these two compounds was the same in the two groups of animals, but their absolute potencies to produce a PCP-like discriminative stimulus were dependent on the training dose of PCP. In contrast, neither the competitive NMDA antagonist CPP (4-20 mg/kg) nor the non-competitive antagonist ifenprodil (2-12 mg/kg) produced PCP-appropriate responding and ifenprodil (4 mg/kg) neither potentiated nor antagonised PCP. These findings are discussed in the light of the hypothesis that the behavioural effects of PCP are mediated via a reduction of neurotransmission at the NMDA-subtype of glutamate receptors.