Effects of N ‐methyl‐ d ‐aspartate agonists and antagonists in rats discriminating amphetamine

Abstract

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 0.25 mg/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.