EFFECTS OF COMPETITIVE AND NONCOMPETITIVE N-METHYL-D-ASPARTATE (NMDA)ANTAGONISTS IN SQUIRREL-MONKEYS TRAINED TO DISCRIMINATE D-CPPENE (SDZ-EAA-494) FROM VEHICLE

Drug discrimination studies have proven useful for comparing and contr asting 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 discri minate 1 mg/kg D-CPPene (2-carboxypiperazine-4-yl)-1-propenyl-1-phosph onic acid; SDZ EAA 494] from vehicle in a two-lever drug discriminatio n procedure. Results show that D-CPPene and several other competitive NMDA antagonists (NPC 17742, CGS 19755, and CGP 37849) completely subs tituted for D-CPPene in a dose-dependent manner. In contrast, phencycl idine (PCP) and ketamine produced only partial substitution at doses t hat severely suppressed response rates. These results are consistent w ith results of earlier studies with rats and monkeys showing differenc es 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 differenc es would be found in the subjective effects of competitive NMDA antago nists and PCP-like non-competitive antagonists.