George F R, Meisch R A
National Institute on Drug Abuse, Addiction Research Center, Baltimore, MD 21224.
Alcohol. 1990 Jul-Aug;7(4):355-60. doi: 10.1016/0741-8329(90)90095-t.
Prostaglandin synthetase inhibitors (PGSIs), which inhibit actions of the enzyme complex cyclooxygenase, significantly antagonize the effects of alcohols but not other sedative-hypnotics across a broad range of measures. This suggests that certain actions of alcohols, in particular ethanol, are mediated at least partially through a prostaglandin-related pathway. This study examined changes in the rate-depressant effects of ethanol in an operant task following pretreatment with either of two PGSIs, indomethacin (INDO) or aspirin (ASP). Water reinforcement maintained the responding of male Sprague-Dawley (SD) rats under a Fixed-Ratio (FR) 32 schedule. Saline, INDO or ASP had no significant effect on control rates of responding. INDO pretreatment significantly antagonized the rate-depressant effects of 1.0 and 1.5 g/kg ethanol. ASP pretreatment also resulted in significant antagonism of ethanol's rate-decreasing effects. INDO was more potent than ASP in antagonizing the rate-depressant effects of ethanol. These results provide further support for the hypothesis that alcohols, by fluidizing neuronal membranes and mobilizing the release of arachidonate, serve to increase prostaglandin production, resulting in some of the behavioral and physiological sequellae of ethanol administration.
前列腺素合成酶抑制剂（PGSIs）可抑制环氧化酶复合物的作用，在广泛的指标范围内能显著拮抗酒精的作用，但对其他镇静催眠药则无此作用。这表明酒精的某些作用，尤其是乙醇的作用，至少部分是通过与前列腺素相关的途径介导的。本研究考察了用两种PGSIs之一吲哚美辛（INDO）或阿司匹林（ASP）预处理后，乙醇在操作性任务中对速率抑制作用的变化。水强化维持雄性Sprague-Dawley（SD）大鼠在固定比率（FR）32程序下的反应。生理盐水、INDO或ASP对对照反应速率无显著影响。INDO预处理显著拮抗了1.0和1.5 g/kg乙醇的速率抑制作用。ASP预处理也导致乙醇速率降低作用的显著拮抗。在拮抗乙醇的速率抑制作用方面，INDO比ASP更有效。这些结果为以下假说提供了进一步支持：酒精通过使神经元膜流化并促进花生四烯酸的释放，从而增加前列腺素的产生，导致乙醇给药后的一些行为和生理后遗症。
