Pentobarbital-like effects of N-methyl-D-aspartate antagonists in mice

The effects of the competitive N-methyl-D-aspartate (NMDA) antagonist, 3-[(+/-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid (CPP), and of the noncompetitive NMDA antagonist, dizocilpine (MK-801), were determined in mice trained to discriminate pentobarbital (20 mg/kg i.p.) from saline under a standard two-lever fixed-ratio 20 schedule of sweetened milk reinforcement. CPP substituted for pentobarbital; however, pentobarbital-lever responding was usually associated with decreases in response rates. Dizocilpine produced a maximum average of only 62% pentobarbital-lever responding, accompanied by a 50% decrease in response rates. These results suggest that pentobarbital-like discriminative stimulus effects are more likely to be produced by competitive than by noncompetitive NMDA antagonists. This extends previous observation in rats and provides further evidence for differences in the behavioral effects of competitive and noncompetitive NMDA antagonists and for an overlap in the behavioral pharmacology of NMDA antagonists and classical CNS depressants.