George F R
National Institute on Drug Abuse, United States Department of Health and Human Services, Baltimore, Maryland 22124.
Ann N Y Acad Sci. 1989;559:382-91. doi: 10.1111/j.1749-6632.1989.tb22624.x.
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.
前列腺素合成抑制剂可拮抗酒精的作用，这表明环氧化酶活性和花生四烯酸代谢的某些方面参与了酒精的作用机制。此外，乙醇会使体内大脑前列腺素E和前列腺素F水平升高，其升高方式在剂量和时间上与乙醇的吸收阶段相关。这些结果为乙醇在很大程度上通过前列腺素介导的机制产生其 intoxicating 作用这一假说提供了系统的证据。本报告概述了这项工作，以及一系列近期研究的其他结果，这些研究考察了用强效前列腺素合成抑制剂吲哚美辛（INDO）预处理对乙醇自我给药的影响。这些自我给药研究的结果表明，吲哚美辛能以剂量相关的方式减少对乙醇的反应。变化模式表明，吲哚美辛通过降低乙醇的强化作用而非通过产生对乙醇的条件性厌恶来减少乙醇自我给药。在随后的一项研究中，吲哚美辛不影响糖精自我给药。这些结果表明，存在一种与前列腺素相关的共同机制，这一机制在介导对乙醇的急性敏感性和该药物的强化特性方面都很重要。这些发现可能为开发针对急性酒精过量以及慢性酒精滥用的新型药物治疗方法提供依据。
