ETHANOL DRUG DISCRIMINATION IN RATS - SUBSTITUTION WITH GABA AGONISTSAND NMDA ANTAGONISTS

Both enhancement of GABAergic neurotransmission and antagonism of glut amatergic neurotransmission involving the NMDA receptor have been impl icated in the acute effects of ethanol. In this study, rats were train ed to discriminate 1000 mg/kg ethanol from saline. This dose of ethano l was consistently discriminated from saline but had no effects on ove rall rates of responding. Substitution tests were conducted with a num ber of GABA agonists and NMDA antagonists. Both midazolam and pentobar bital exhibited substantial substitution for ethanol at doses that mod erately decreased response rates. However, muscimol and baclofen compl etely failed to substitute for ethanol, as did a combination of a fixe d dose of muscimol with increasing doses of baclofen. The non-competit ive NMDA antagonists PCP, dizocilpine and ketamine substituted fully f or ethanol, but only at doses that also substantially suppressed rates of responding. The competitive NMDA antagonists, CPPene and NPC 17742 , partially substituted for ethanol. The levels of substitution for et hanol among the indirect GABA agonists and the non-competitive NMDA an tagonists indicate that the discriminative stimulus effects of ethanol , at least at a 1000 mg/kg dose, may involve both GABAergic and glutam atergic systems.