Tolerance to the discriminative stimulus effects of ethanol

These experiments tested (1) the specificity of the discriminative stimulus produced by ethanol (EtOH), (2) the ability of Ro 15-4513 to block the EtOH stimulus, and (3) whether tolerance would develop to the discriminative effects of EtOH following high-dose EtOH administration. Rats were trained to use EtOH, 1 g/kg, i.p., as a discriminative stimulus in a two-choice, food-reward task. Following establishment of stimulus control, EtOH and pentobarbital substituted for EtOH in a dose-related manner; in contrast, pentylene-tetrazole and cocaine produced responding on the vehicle lever. Ro 15-4513, a partial inverse agonist at benzodiazepine receptors, failed to block the EtOH stimulus. Following these experiments, subjects were withheld from training and given EtOH in a nutritionally complete liquid diet, in two feedings per day for 6 days. Subjects consumed approximately 10 g of EtOH per day from this diet. On days 4 to 6 of this regimen, 12-h after a previous EtOH feeding, subjects were retested with EtOH. After recovery from this procedure and re-establishment of baseline performance, subjects were again given the high-dose EtOH treatment and tested for pentobarbital substitution. High-dose EtOH produced tolerance to EtOH and some degree of cross-tolerance to pentobarbital. These results are consistent with the hypothesis that chronic EtOH administration produces tolerance to the stimulus effects of EtOH.