Effects of competitive and non-competitive N-methyl-D-aspartate (NMDA) antagonists in squirrel monkeys trained to...

Drug discrimination studies have proven useful for comparing and contrasting the behavioral effects of site-selective N-methyl-D-aspartate (NMDA) antagonists. This study examined the effects of competitive and non-competitive NMDA antagonists in squirrel monkeys trained to discriminate 1 mg/kg D-CPPene [D-3-(2-carboxypiperazine-4-yl)-1- propenyl-1-phosphonic acid; SDZ EAA 494] from vehicle in a two-lever drug discrimination procedure. Results show that D-CPPene and several other competitive NMDA antagonists (NPC 17742, CGS 19755, and CGP 37849) completely substituted for D-CPPene in a dose-dependent manner. In contrast, phencyclidine (PCP) and ketamine produced only partial substitution at doses that severely suppressed response rates. These results are consistent with results of earlier studies with rats and monkeys showing differences in the discriminative stimulus effects of competitive and PCP-like non-competitive NMDA antagonists. The data support the predictions (1) that D-CPPene and the other competitive NMDA antagonists tested would have similar subjective effects in humans and (2) that some differences would be found in the subjective effects of competitive NMDA antagonists and PCP-like non-competitive antagonists.