Pharmacological specificity of the phencyclidine discriminative stimulus in rats

The discriminative stimulus effects of phencyclidine (PCP), pentobarbital and the competitive N-methyl-D-aspartate antagonist 3-([+/-]-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) were examined in rats trained to discriminate PCP from saline under a 2-lever, food-maintained operant schedule. Dose-response curves were obtained for all three drugs at a PCP training dose of 1.25 mg/kg; subsequently, rats were retrained to discriminate either 0.56 or 3.0 mg/kg PCP. The dose-response to PCP was not substantially changed by raising or lowering the training dose. However, doses of pentobarbital and CPP produced augmented levels of substitution when the training dose was lowered and decreased substitution when it was raised. The changes in PCP training dose were, therefore, effective in either diminishing or amplifying the pharmacological specificity of the PCP stimulus. Under conditions where specificity was high (high training dose), neither pentobarbital (0.1-17 mg/kg) nor CPP (1-17 mg/kg) produced appreciable PCP-like stimulus effects, supporting evidence that competitive NMDA antagonists may be no more PCP-like than are barbiturates. These data provide additional evidence for differences in the behavioral effects of noncompetitive and competitive NMDA antagonists.