The role of arachidonic acid metabolites in mediating ethanol self-administration and intoxication.
Prostaglandin synthesis inhibitors antagonize the effects of alcohols, indicating that some aspect of cyclooxygenase activity and arachidonic acid metabolism is involved in the mechanism of action of alcohols. In addition, ethanol increases in vivo brain PGE and PGF levels in a manner correlated across dose and time with the absorption phase of ethanol. These results have provided systematic evidence in support of the hypothesis that ethanol produces its intoxicating effects to a significant degree through a prostaglandin-mediated mechanism. This report has presented an overview of this work, as well as additional results from a series of recent studies that examined the effects of pretreatment with INDO, a potent PGSI, on ethanol self-administration. The results of these self-administration studies indicate that INDO can decrease responding for ethanol in a dose-related manner. The pattern of changes suggests that INDO decreases ethanol self-administration by decreasing the reinforcing effects of ethanol and not by producing a conditioned aversion to ethanol. In a subsequent study, INDO did not affect saccharin self-administration. These results suggest that there exists a common prostaglandin-related mechanism that is important in the mediation of both acute sensitivity to ethanol and the reinforcing properties of this drug. These findings may provide for the development of novel pharmaceutical treatments for acute alcohol overdose as well as for chronic alcohol abuse.
National Institute on Drug Abuse, United States Department of Health and Human Services, Baltimore, Maryland 22124.
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D000435:Alcoholic Intoxication; D000818:Animals; D001095:Arachidonic Acids / Q000502:physiology*; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012439:Saccharin; D012646:Self Administration
D001095:Arachidonic Acids; D000431:Ethanol; D012439:Saccharin; D007213:Indomethacin