EFFECT OF THE 5-HT3 ANTAGONIST ONDANSETRON ON VOLUNTARY ETHANOL INTAKE IN RATS AND MICE MAINTAINED ON A LIMITED ACCESS PROCEDURE

The effect of the 5-HT3 antagonist ondansetron on ethanol self-adminis tration was examined in a limited access paradigm. Acute administratio n of ondansetron (0.01 and 0.1 mg/kg) reduced ethanol intake in male W istar rats by 35%, whilst water intake was unaffected. Both a lower (0 .001 mg/kg) and higher dose (1 mg/kg) of ondansetron failed to modify ethanol consumption. Ondansetron did not, however, alter the pharamaco kinetic profile of an orally administered dose of ethanol (1 g/kg) ove r the same dose range. To examine the generality of these findings and to determine if tolerance would develop to the suppressant effects of ondansetron on ethanol intake, male C57BL/6 mice were treated with on dansetron (0.001, 0.01 and 0.1 mg/kg) over 22 days, 30 min prior to sc heduled access to ethanol. Both 0.01 and 0.1 mg/kg doses reduced ethan ol intake; however, water intake was not altered by either dose. This finding confirms and extends the generality of the effects of 5-HT3 re ceptor antagonists on ethanol intake across different species and diff erent paradigms of ethanol consumption. More importantly, the present study shows that the reduction in ethanol intake induced by ondansetro n was maintained even after a prolonged period of treatment and is not due to an alteration in the absorption or metabolism of ethanol.