SEROTONIN 5-HT3 ANTAGONISTS FAIL TO AFFECT ETHANOL SELF-ADMINISTRATION OF RATS

Five Long-Evans hooded rats were trained to lever press according to fixed-ratio 5 reinforcement schedules for 0.06 ml dipper deliveries of 8% w/v ethanol during daily (M-F) 0.5-h experimental sessions. After ethanol self-administration was established, doses of the serotonin 5-HT3 antagonists, ondansetron (0.03-3.0 mg/kg), granisetron (0.01-1.0 mg/kg), and SC-51296 (0.1-10.0 mg/kg) were administered prior to ethanol sessions to determine their effects on ethanol self-administration. None of the doses of the antagonists had significant effects on numbers of obtained ethanol deliveries. Subsequently, each antagonist (ondansetron, 0.1 mg/kg; granisetron, 0.3 mg/kg; SC-51296, 0.1 mg/kg) was administered b.i.d. for five consecutive daily sessions. During none of these chronic tests with the 5-HT3 antagonists were there significant main effects of drug administration. Overall, these results do not support the hypothesis that the serotonin 5-HT3 antagonists would have robust therapeutic efficacy in the treatment of alcoholism.