Collins A C, Gilliam D M, Miner L L
Alcohol Clin Exp Res. 1985 Jul-Aug;9(4):371-6. doi: 10.1111/j.1530-0277.1985.tb05562.x.
Previous reports from our laboratory have indicated that the responses to ethanol following intraperitoneal (i.p.) injection increase as the concentration of the ethanol solution increases. We have also presented evidence which indicates that pretreatment with drugs such as indomethacin (a prostaglandin synthetase inhibitor) decreases the response of mice to ethanol injected i.p. The results reported here corroborate our earlier findings in that the sleep time response of C57BL and DBA mice was greater following injection with a 40% (w/v) ethanol solution than that seen following i.p. injection with a 20% (w/v) ethanol solution. The increase in sleep time does not appear to be due to alterations in the rates of absorption or elimination of ethanol. Pretreatment with indomethacin reduced sleep time in those animals injected with the 40% solution but was without effect in the animals injected with the 20% solution. Both C57BL and DBA mice pretreated with indomethacin exhibited an increase in waking blood and brain ethanol, an indicant of altered central nervous system sensitivity. In addition, both DBA and C57BL mice exhibited an increase in the linear rate of ethanol elimination if pretreated with indomethacin before injection with the 40% ethanol solution. Indomethacin did not affect ethanol elimination rates of animals injected with the 20% ethanol solution. These data indicate that high concentrations of ethanol when injected into the peritoneal cavity promote the production of prostaglandins which serve to enhance the behavioral response to ethanol. This enhancement may be due to altered pharmacokinetics as well as central nervous system effects.
我们实验室之前的报告表明，腹腔注射乙醇后的反应会随着乙醇溶液浓度的增加而增强。我们还提供了证据表明，用消炎痛（一种前列腺素合成酶抑制剂）等药物进行预处理会降低小鼠对腹腔注射乙醇的反应。此处报告的结果证实了我们早期的发现，即C57BL和DBA小鼠注射40%（w/v）乙醇溶液后的睡眠时间反应比腹腔注射20%（w/v）乙醇溶液后的反应更大。睡眠时间的增加似乎不是由于乙醇吸收或消除速率的改变。用消炎痛预处理可减少注射40%溶液的动物的睡眠时间，但对注射20%溶液的动物没有影响。用消炎痛预处理的C57BL和DBA小鼠的清醒血液和脑乙醇含量均增加，这表明中枢神经系统敏感性发生了改变。此外，如果在注射40%乙醇溶液前用消炎痛预处理，DBA和C57BL小鼠的乙醇消除线性速率均会增加。消炎痛对注射20%乙醇溶液的动物的乙醇消除速率没有影响。这些数据表明，腹腔注射高浓度乙醇会促进前列腺素的产生，而前列腺素会增强对乙醇的行为反应。这种增强可能是由于药代动力学改变以及中枢神经系统效应。
