Effects of ondansetron pretreatment on acute responses to ethanol in social drinkers

Laboratory animal and clinical studies suggest that the 5-HT(3) receptor subtype may mediate some of the CNS effects of ethanol. Two experiments were conducted to evaluate the effects of the 5-HT(3) receptor antagonist, ondansetron, on the acute responses of social drinkers to a moderate dose of ethanol. In Experiment 1, two doses of ondansetron (0.15 and 0.30mg) or placebo were tested in combination with ethanol (0.5g/kg) or placebo. In Experiment 2, three higher doses of ondansetron (1.0, 3.0 and 10.0mg) or placebo were tested in combination with ethanol (0.5g/kg) or placebo. Sessions were conducted one or two evenings per week from 16.00h until 20.45h. Separate groups of subjects participated in the two placebo-controlled, double-blind experiments (Experiment 1: n = 13; Experiment 2: n = 6). The order of drug administration was counterbalanced across subjects. In each study, subjects were given an intravenous infusion of ondansetron and 5min later consumed an ethanol or placebo beverage. For 3h 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 ondansetron alone did not differ significantly from placebo. Ethanol alone produced prototypic effects on several measures (e.g., increased ratings of "positive" subjective effects and impaired memory performance). Furthermore, ondansetron pretreatment did not modify physiological, subjective or performance effects of ethanol. These findings do not support the hypothesis that the 5-HT(3), receptor/channel complex mediates the positive subjective effects, or any other subjective or performance effects, of ethanol.