Effects of the 5-HT3 antagonist ICS 205-930 on benzodiazepine withdrawal signs in rats

Effects of the 5-HT3 antagonist ICS 205-930 on chlordiazepoxide (CDP) withdrawal were assessed in rats treated for 21 days with doses of CDP up to 40mg/kg/day (b.i.d.). Withdrawal signs recorded were body weight and 24h food intake, which both fell during withdrawal and then recovered. ICS 205-930 (0.001-1.0mg/kg) was administered b.i.d. during withdrawal. At no dose over the wide range tested did ICS 205-930 reduce withdrawal signs. These data contrast with published findings with the 5-HT3 antagonist ondanestron, some of which indicated that ondansetron completely alleviated the "anxiogenic" suppression of exploratory behaviour observed during benzodiazepine (BZ) withdrawal. Possible reasons for these differing findings are discussed. Collectively, these findings suggest that 5-HT3 antagonists may have limited utility in the clinical treatment of BZ withdrawal.