Effects of N-methyl-D-aspartate agonists and antagonists in rats discriminating amphetamine

The present study assessed the interactions between N-methyl-D-aspartate (NMDA) agonists or antagonists and the discriminative stimulus effects of amphetamine. Adult male Sprague-Dawley rats were trained to discriminate 0.5 mg/kg (i.p.) of amphetamine from saline under a two-lever fixed-ratio schedule of food reinforcement. During test sessions, i.p. injections of the glycine site agonist D-cycloserine, the ion-channel blocker dizocilpine and the competitive antagonist CGP 43487 were coadministered with i.p. saline or with a full range of doses of amphetamine. D-Cycloserine did not substitute for amphetamine and attenuated the cueing effects of the drug. Both dizocilpine and CGP 43487 engendered intermediate levels of amphetamine-appropriate responses and potentiated the stimulus properties of amphetamine; however, the effects of CGP 43487 were very small and not dose-dependent. In an ancillary experiment, the training dose of amphetamine was reduced to 0.25mg/kg; under these conditions dizocilpine, but not CGP 43487, produced full substitution for the discriminative stimulus effects of amphetamine. These results show that drugs affecting NMDA receptor-based neurotransmission can modulate the discriminative stimulus effects of amphetamine.