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.
Beardsley
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G. D. Searle & Co., Neurological Diseases Research Dept., Skokie, IL 60077.
Lopez
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OT
Gullikson
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Flynn
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D000437:Alcoholism / Q000188:drug therapy; D000818:Animals; D000431:Ethanol / Q000008:administration & dosage*; D017829:Granisetron / Q000008:administration & dosage / Q000494:pharmacology; D007191:Indazoles / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D017294:Ondansetron / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D012054:Reinforcement, Psychology; D012646:Self Administration; D012702:Serotonin Antagonists / Q000494:pharmacology*
D000431:Ethanol; D017829:Granisetron; D007191:Indazoles; D017294:Ondansetron; D012702:Serotonin Antagonists; C091452:SC 51296