Competitive and noncompetitive N-methyl-D-aspartate (NMDA) antagonists, haloperidol, and scopolamine impair performance in a nonspatial operant discrimination task

The actions of competitive (NPC 12626 and CPP) and noncompetitive (PCP and MK 801) N-methyl-D-aspartate (NMDA) antagonists on performance of a nonspatial, operant repeated discrimination task were examined. The effects of the reference agents scopolamine and haloperidol were also examined. The competitive NMDA antagonist CPP, the noncompetitive NMDA antagonist MK 801, and scopolamine increased the number of responses necessary to attain discrimination criterion. Only MK 801 simultaneously reduced the probability of a response during a trial and increased the probability of an intertrial interval response. Haloperidol reduced the number of sessions with a reliable number of responses but did not alter the total number of responses to criterion. The results suggest that both competitive and noncompetitive NMDA antagonists can disrupt cognitive processes that are involved in a variety of learning tasks, including nonspatial discrimination.