Belknap J K, Mitchell M A
J Pharmacol Exp Ther. 1981 Sep;218(3):647-52.
Chronic exposure to phenobarbital at a 21-22 degrees C ambient temperature produced marked hypothermia in C57BL/6J male mice, to which functional tolerance gradually developed over a 6.5 day intoxication period. Soon after phenobarbital withdrawal, marked hypothermia again developed, reaching its maximal extent at a time when tremors, convulsions on handling and Straub tail were at their peak frequency. When these mice were placed in a 34 degrees C ambient environment, which prevents the hypothermia, these withdrawal signs were eliminated or greatly reduced in frequency compared to mice at 22 degrees C, whereas the incidence of tonic-clonic seizures was not significantly affected. Core body temperature was found to correlate significantly with the degree of gross intoxication during the intoxication phase and with the withdrawal signs of tremor and Straub tail after withdrawal of the drug. When mice were given a choice between a 23 and a 35 degrees C environment at times of maximal hypothermia, their choice often served to maintain the hypothermic state rather than to reduce it. These results suggest that some of the signs of withdrawal (tremor and Straub tail) may be (in part) secondary responses to a primary dysfunction, which is thermoregulatory in nature.
在21 - 22摄氏度的环境温度下，对C57BL/6J雄性小鼠进行长期苯巴比妥暴露会导致显著的体温过低，在6.5天的中毒期内，小鼠会逐渐产生功能性耐受。苯巴比妥撤药后不久，体温过低现象再次出现，在震颤、抓握时抽搐和斯特劳布尾（Straub tail）频率达到峰值时，体温过低达到最大程度。当将这些小鼠置于34摄氏度的环境中（该环境可防止体温过低）时，与处于22摄氏度环境中的小鼠相比，这些撤药症状的频率会消除或大大降低，而强直阵挛性癫痫发作的发生率则没有受到显著影响。研究发现，在中毒阶段，核心体温与总体中毒程度显著相关，在药物撤药后，核心体温与震颤和斯特劳布尾等撤药症状也显著相关。当小鼠在体温过低达到最大值时，在23摄氏度和35摄氏度的环境之间进行选择时，它们的选择往往是维持低温状态而非降低低温。这些结果表明，某些撤药症状（震颤和斯特劳布尾）可能（部分）是对一种原发性功能障碍的继发反应，这种原发性功能障碍本质上是体温调节方面的。
