EFFECTS OF ONDANSETRON PRETREATMENT ON ACUTE RESPONSES TO ETHANOL IN SOCIAL DRINKERS

Laboratory animal and clinical studies suggest that the 5-HT3 receptor subtype may mediate some of the CNS effects of ethanol. Two experimen ts were conducted to evaluate the effects of the 5-HT3 receptor antago nist, ondansetron, on the acute responses of social drinkers to a mode rate dose of ethanol. In Experiment 1, two doses of ondansetron (0.15 and 0.30 mg) or placebo were tested in combination with ethanol (0.5) g/kg or placebo. In Experiment 2, three higher doses of ondansetron (1 .0, 3.0 and 10.0 mg) or placebo were tested in combination with ethano l (0.5 g/kg) or placebo. Sessions were conducted one or two evenings p er week from 16.00 h until 20.45 h. Separate groups of subjects partic ipated in the two placebo-controlled, double-blind experiments (Experi ment 1: n = 13; Experiment 2: n = 6). The order of drug administration was counterbalanced across subjects. In each study, subjects were giv en an intravenous infusion of ondansetron and 5 min later consumed an ethanol or placebo beverage. For 3 h after the beverage was consumed, physiological, subjective effects and performance measures were taken at regular intervals. Across a wide range of doses, the effects of ond ansetron alone did not differ significantly from placebo. Ethanol alon e produced prototypic effects on several measures (e.g., increased rat ings of ''positive'' subjective effects and impaired memory performanc e). Furthermore, ondansetron pretreatment did not modify physiological , subjective or performance effects of ethanol. These findings do not support the hypothesis that the 5-HT3 receptor/channel complex mediate s the positive subjective effects, or any other subjective or performa nce effects, of ethanol.