Alkana R L, Bejanian M, Syapin P J, Finn D A
Life Sci. 1987 Jul 27;41(4):413-20. doi: 10.1016/0024-3205(87)90216-5.
Previous studies have found that body temperature during intoxication influences brain sensitivity to ethanol with the sensitivity being less at cool than at warm body temperatures. If this effect of temperature reflects alterations in the acute membrane perturbing action of ethanol, as suggested by in vitro studies, then body temperature reduction (hypothermia) during tolerance acquisition should reduce the effectiveness of a given ethanol concentration and, in turn, should reduce the development of chronic functional ethanol tolerance. To test this hypothesis, adult drug-naive C57BL/6J mice were injected i.p. once daily for five days with 3.6 g/kg ethanol (20% w/v) and were exposed to 34 degrees C or 25 degrees C for five hours following injection. On day 6, both ethanol acquisition groups and naive mice were injected i.p. with 4.0 g/kg ethanol and exposed to 25 degrees C. During acquisition, the group exposed to 34 degrees C had significantly higher body temperatures than the mice exposed to 25 degrees C, and there were no statistically significant differences in blood ethanol concentrations between treatment conditions. The extent of tolerance on day 6, measured by sleep-times and wake-up blood and brain ethanol concentrations versus naive mice, was significantly greater in the 34 degrees C acquisition group than in the 25 degrees C acquisition group. The results demonstrate that body temperature influences tolerance development in the manner predicted by membrane perturbation theories of anesthesia and adaptation based tolerance theories.
先前的研究发现，中毒期间的体温会影响大脑对乙醇的敏感性，凉爽体温下的敏感性低于温暖体温时。如果温度的这种影响反映了乙醇急性膜扰动作用的改变，正如体外研究表明的那样，那么在耐受性形成过程中体温降低（体温过低）应该会降低给定乙醇浓度的效力，进而应该会减少慢性功能性乙醇耐受性的发展。为了验证这一假设，成年未接触过药物的C57BL/6J小鼠每天腹腔注射一次3.6克/千克乙醇（20% w/v），持续五天，并在注射后暴露于34摄氏度或25摄氏度环境中五小时。在第6天，两个乙醇给药组和未接触过乙醇的小鼠均腹腔注射4.0克/千克乙醇，并暴露于25摄氏度环境中。在给药期间，暴露于34摄氏度环境中的组体温显著高于暴露于25摄氏度环境中的小鼠，且不同处理条件下的血液乙醇浓度无统计学显著差异。通过睡眠时间以及苏醒时血液和大脑中的乙醇浓度与未接触过乙醇的小鼠相比来衡量，第6天34摄氏度给药组的耐受性程度显著高于25摄氏度给药组。结果表明，体温以麻醉的膜扰动理论和基于适应的耐受性理论所预测的方式影响耐受性的发展。
