Drug discrimination analysis of ethanol as an N-methyl-D-aspartate receptor antagonist

Ethanol has been shown to antagonize N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission in a number of in vitro systems. Drug discrimination procedures in rats were used to evaluate ethanol as an antagonist of NMDA discrimination and for its ability to produce discriminative stimulus effects similar to those of competitive and noncompetitive NMDA antagonists. Ethanol (300-1500 mg/kg i.p.) failed to antagonize the stimulus effects of 30 mg/kg NMDA, nor did it substitute fully for either the competitive antagonist NPC 12626 nor the noncompetitive antagonist phencyclidine (PCP). A maximum average of 55.4% PCP-lever responding provided evidence for partial substitution in this model. The effects of ethanol on NMDA discrimination are distinct from those previously reported for competitive NMDA antagonists but similar to those of noncompetitive antagonists. On the other hand, ethanol can be distinguished from both competitive and PCP-like noncompetitive NMDA antagonists using drug discrimination procedures.