5-HT3 antagonist ICS 205-930 enhances naltrexone's effects on ethanol intake.

Opioid receptor antagonist naltrexone has shown some efficacy in decreasing ethanol consumption in humans. However, naltrexone treatment is not always efficacious and produces several aversive effects such as nausea, anxiety and weight loss. Serotonin-3 (5-HT3) receptor antagonists also modulate some of the behavioral effects of alcohol and may decrease alcohol consumption. We examined the effects of the combination of 5-HT3 receptor antagonist ICS 205–930 ((3-tropanyl-indole-1-carboxylate, tropisetron) and naltrexone on ethanol and food intake in Sprague–Dawley rats. Both naltrexone (0.56–10 mg/kg) and ICS 205–930 (5.6 mg/kg), when administered intraperitoneally 30 min before the scheduled 3-h access to ethanol, significantly suppressed ethanol intake. Naltrexone (1 mg/kg) when given in combination with ICS 205–930 (5.6 mg/kg) was significantly more efficacious in suppressing ethanol intake in comparison with naltrexone (1 mg/kg) administered alone. The drug combination did not affect the food intake. These data suggest that 5-HT3 receptor antagonist ICS 205–930 may be used as an effective adjunct for pharmacotherapy of alcoholism.