ATTENUATION OF THE DISCRIMINATIVE STIMULUS EFFECTS OF ETHANOL BY THE BENZODIAZEPINE PARTIAL INVERSE AGONIST RO-15-4513

The aim of the present study was to investigate whether ethanol traini ng affects the ability of Ro 15-4513 to block the discriminative stimu lus effects of ethanol dose differentially. Three different groups of rats were trained to discriminate 1.0 g/kg ethanol (n =8), 1.5 g/kg et hanol (n = 7) or 2.0 g/kg ethanol (n =8) from water in a two-lever, fo od-reinforced procedure. Ethanol and water were administered by gavage 20 min before the onset of the session. When the discrimination perfo rmance was stable, rats mere pretreated with Ro 15-4513 (1-17 mg/kg; i .p.) 5 min before the administration of ethanol. Ro 15-4513 attenuated the discriminative stimulus effects of 1.0 and 1.5 g/kg ethanol but n ot 2.0 g/kg ethanol in each of the ethanol training groups. Overall, b lockade of the discriminative stimulus effects of 1.0 and 1.5 g/kg eth anol by 5.6 mg/kg Ro 15-4513 occurred without significantly altering r esponse rates or blood ethanol concentrations. A decrease in blood eth anol concentration was, however, found with 17 mg/kg Ro 15-4513 in com bination with 2.0 g/kg ethanol. These results suggest that the benzodi azepine partial inverse agonist, Ro 15-4513, can attenuate the discrim inative stimulus effects associated with low to moderate doses of etha nol (1.0-1.5 g/kg).