Repeated ethanol withdrawal experience increases the severity and duration of subsequent withdrawal seizures in mice
Repeated ethanol withdrawal experience increases the severity and duration of subsequent withdrawal seizures in mice
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DOI：
10.1016/s0741-8329(97)87949-9
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发表时间：
1997-07-01
期刊：
影响因子：
2.3
通讯作者：
Weathersby, RT
中科院分区：
文献类型：
--
作者：
Becker, HC;DiazGranados, JL;Weathersby, RT
反复的乙醇戒断经验已被证明会导致未来戒断事件的加重。这种退缩反应的感觉被假设为代表一种“点燃”现象。本研究的目的是检查是否有系统的增加，在以前的乙醇戒断经验的数量增加的严重程度和随后的戒断反应的持续时间。采用已建立的重复乙醇中毒/戒断模型，其中成年C3 H小鼠在吸入室中长期暴露于乙醇蒸气。在第一个实验中，多次戒断（MW）组小鼠接受9个（MWx 9）、6个（MWx 6）或3个（MWx 3）周期的16小时乙醇暴露;对照（C）组在整个实验中未接受任何乙醇处理。在第二个实验中，一组小鼠（MW 1 -9）在9个戒断周期内重复测试。第三项实验旨在评估重复吡唑给药对增强的戒断性癫痫发作反应的影响。结果表明，先前经历的乙醇戒断次数与随后戒断事件的严重程度和持续时间之间存在正相关关系。停药评估前，所有乙醇暴露组的血液乙醇水平相似。此外，在9个中毒/戒断周期内，戒断性癫痫发作（处理诱导的惊厥）的强度逐渐增加，重复测试对这种增强反应的发展没有显著影响。此外，吡唑重复给药似乎不会影响这种戒断致敏现象。总的来说，这些结果为乙醇戒断的“点燃”假说提供了进一步的支持。
Repeated ethanol withdrawal experience has been shown to result in an exacerbation of future withdrawal episodes. This sensation of the withdrawal response has been hypothesized to represent a ''kindling'' phenomenon. The present study was designed to examine whether a systematic increase in the number of previous ethanol withdrawal experiences increases both the severity and duration of a subsequent withdrawal response. An established model of repeated ethanol intoxication/withdrawal was employed in which adult C3H mice were chronically exposed to ethanol vapor in inhalation chambers. In the first experiment, multiple withdrawal (MW) groups of mice received nine (MWx9), six (MWx6), or three (MWx3) cycles of 16-h ethanol exposure; and a control (C) group did not receive any ethanol treatment throughout the experiment. In a second experiment, a group of mice (MW1-9) were repeatedly tested over nine cycles of withdrawal. A third experiment was designed to assess the effects of repeated pyrazole administration on the potentiated withdrawal seizure response. Results indicated a positive relationship between the number of previously experienced ethanol withdrawals and the severity and duration of a subsequent withdrawal episode. Blood ethanol levels were similar for all ethanol-exposed groups prior to withdrawal assessment. Further, the intensity of withdrawal seizures (handling-induced convulsions) progressively increased over nine cycles of intoxication/withdrawal and repeated testing did not significantly influence the development of this potentiated response. In addition, repeated administration of pyrazole did not appear to influence this withdrawal sensitization phenomenon. Collectivity, these results provide further support for the ''kindling'' hypothesis of ethanol withdrawal.