George F R, Howerton T C, Elmer G I, Collins A C
Pharmacol Biochem Behav. 1983 Jul;19(1):131-6. doi: 10.1016/0091-3057(83)90321-0.
Pretreatment of mice with prostaglandin synthetase inhibitors (PGSI's) antagonizes alcohol-induced behaviors. This study examined genetic and time course factors of this effect and studied the effects of a putative prostaglandin antagonist (SC-19220) on ethanol sleep time. Long Sleep (LS) and Short Sleep (SS) mice, lines bred for differential response to an hypnotic dose of ethanol, showed a four-fold difference in their dose-response curves for indomethacin antagonism of ethanol-induced hypnosis. Females of both lines required higher amounts of indomethacin relative to males. Indomethacin pretreated animals regained the righting response at a higher blood ethanol concentration than did saline pretreated animals. In addition, indomethacin pretreatment failed to alter the rate of ethanol disappearance from blood. In general, both lines showed effects with low doses of indomethacin at early time points and with high doses of indomethacin at later time points. Indomethacin did not antagonize ethanol-induced hypnosis if given after ethanol. In C3H mice, pretreatment with low doses of SC-19220, a dibenzoxazepine derivative, produced a significant decrease in ethanol sleep time, moderate doses produced no effect, and high levels increased sleep time. These results further substantiate and expand our previous reports. Possible mechanisms for the biphasic effects of indomethacin treatment are presented and discussed.
用前列腺素合成酶抑制剂（PGSI）对小鼠进行预处理可对抗酒精诱导的行为。本研究考察了这种效应的遗传和时间进程因素，并研究了一种假定的前列腺素拮抗剂（SC - 19220）对乙醇睡眠时间的影响。长睡眠（LS）和短睡眠（SS）小鼠是为对催眠剂量乙醇的不同反应而培育的品系，它们在吲哚美辛拮抗乙醇诱导催眠的剂量反应曲线上显示出四倍的差异。两个品系的雌性相对于雄性需要更高剂量的吲哚美辛。与生理盐水预处理的动物相比，吲哚美辛预处理的动物在更高的血液乙醇浓度时恢复翻正反射。此外，吲哚美辛预处理未能改变乙醇从血液中消失的速率。一般来说，两个品系在早期时间点用低剂量吲哚美辛显示出效应，在后期时间点用高剂量吲哚美辛显示出效应。如果在乙醇给药后给予吲哚美辛，则它不会拮抗乙醇诱导的催眠。在C3H小鼠中，用低剂量的二苯并恶唑嗪衍生物SC - 19220进行预处理可使乙醇睡眠时间显著缩短，中等剂量无作用，高剂量则延长睡眠时间。这些结果进一步证实并扩展了我们之前的报告。本文提出并讨论了吲哚美辛治疗双相效应的可能机制。
