Substitution by NMDA antagonists and other drugs in rats trained to discriminate ethanol

It has been reported that, in animals trained to discriminate ethanol, stimulus control generalized to the non-competitive NMDA antagonists phencyclidine, ketamine and dizocilpine. In the present study, rats were trained to discriminate a dose of ethanol (1g/kg, i.p.) and substitution tests were carried out with phencyclidine, dizocilpine, CGS 19755, eliprodil, triazolam, chlordiazepoxide, abecarnil, alpidem and d-amphetamine. Phencyclidine and dizocilpine produce dose-related substitution for ethanol as did the competitive NMDA antagonist, CGS 19755, and the benzodiazepines, triazolam and chlordiazepoxide. Eliprodil, an NMDA antagonist acting through the polyamine modulatory site, neither substituted for ethanol nor modified the ethanol dose-response curve. d-Amphetamine, and the non-benzodiazepine anxiolytics, alpidem and abecarnil, did not substitute for ethanol. The results show that both NMDA antagonists and compounds acting through (GABA receptors (benzodiazepines) can substitute for ethanol, emphasizing that the ethanol cue may involve several mechanisms. As all the drugs substituting for ethanol, like ethanol itself, are known to produce ataxia and muscle relaxation, it is proposed that this property may be an important aspect of the ethanol cue.