ONDANSETRON ALTERS HUMAN ALCOHOL-INTOXICATION

There is considerable evidence that serotonin-3 (5-HT3) receptor antag onists modulate some of the behavioral effects of alcohol, and may dec rease alcohol consumption. To better clarify the mechanism of action o f 5-HT3 antagonists on these behaviors, we investigated the effects of the 5-HT3 antagonist, ondansetron, on several subjective and objectiv e measures of alcohol intoxication in social drinkers. Twelve nonalcoh olic, social drinkers received either 8 mg ondansetron, p.o., or place bo during one of two test sessions in a crossover, double-blind protoc ol. Both conditions were followed by a standard, intoxicating dose of alcohol. Subjective and objective measures of intoxication including m ood, physical sensations, performance changes, and alcohol pharmacokin etics were determined. To control for ondansetron effects, 10 addition al subjects received either ondansetron or placebo, followed by a noni ntoxicating, ''placebo'' dose of alcohol during a second crossover dou ble-blind protocol. Ondansetron was found to augment certain stimulant , sedative, and discriminant effects of alcohol, without affecting psy chomotor performance or alcohol pharmacokinetics. Ondansetron had mini mal effects on subjects receiving placebo alcohol. These data suggest that the reductions in alcohol consumption observed in animals and hum ans treated with ondansetron may be mediated by increases in subjectiv e intoxication, and/or increases in the aversive effects of alcohol.