Discriminative stimulus effects of ethanol: lack of antagonism with N-methyl-D-aspartate and D-cycloserine.

Several drug discrimination studies reported that both competitive and uncompetitive NMDA receptor antagonists substituted for ethanol stimulus in rats. In the present study we examined if compounds that act as agonists at the NMDA receptor complex, D-cycloserine (a partial agonist at the glycine positive modulatory site) and N-methyl-D-aspartate (an agonist at the glutamate binding site), could antagonize the discriminative stimulus effects of ethanol. Rats were trained to discriminate between IP administered 1.0 g/kg of ethanol (10% v/v) and saline under a sweetened milk-reinforced fixed ratio 10 (FR10) schedule of reinforcement. When the animals met the discriminative criteria, antagonism tests were conducted with D-cycloserine (0.3-10.0 mg/kg, IP) and N-methyl-D-aspartate (15.0-60.0 mg/kg, IP). Neither D-cycloserine nor N-methyl-D-aspartate antagonized the ethanol-mediated discriminative stimulus effects. In addition, D-cycloserine (3.0-300.0 mg/kg, IP) did not substitute for ethanol. These results indicate that at least certain agonists at the NMDA receptor complex do not attenuate the ethanol interoceptive cue in the rat.