Finn D A, Roberts A J, Crabbe J C
Research Service (151C), Department of Veterans Affairs Medical Center, Hospital Road, Portland, OR 97201, USA.
Alcohol Clin Exp Res. 1995 Apr;19(2):410-5. doi: 10.1111/j.1530-0277.1995.tb01523.x.
Withdrawal Seizure-Prone (WSP) and -Resistant (WSR) mice, which were selectively bred for severe (WSP) or mild (WSR) handling-induced convulsions (HICs) following chronic ethanol inhalation, were found to differ in sensitivity to the anticonvulsant effects of the neuroactive steroid 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-P. 3 alpha,5 alpha-P (5 or 10 mg/kg, ip) significantly increased seizure thresholds to pentylenetetrazol in ethanol-native males of both the WSP and WSR lines. In general, WSP mice were more sensitive than WSR mice to the anticonvulsant effect of 3 alpha,5 alpha-P. Subsequent studies in male WSP mice exposed to ethanol vapor or air for 24 hr demonstrated enhanced sensitivity to the anticonvulsant effect of 3 alpha,5 alpha-P (0.5-20 mg/kg, ip) during ethanol withdrawal. Only the highest dose affected HICs in air-exposed animals, whereas both the two highest doses significantly reduced HICs in ethanol-exposed mice. These results provide the first demonstration that 3 alpha,5 alpha-P attenuates ethanol withdrawal convulsions and indicate enhanced sensitivity to the anticonvulsant effect of 3 alpha,5 alpha-P in animals withdrawing from ethanol dependence.
对慢性吸入乙醇后因重度（撤药惊厥易感性，WSP）或轻度（撤药惊厥抗性，WSR）处理诱导惊厥（HICs）而进行选择性培育的小鼠进行研究发现，它们对神经活性甾体3α-羟基-5α-孕烷-20-酮（3α,5α-P）的抗惊厥作用敏感性存在差异。3α,5α-P（5或10毫克/千克，腹腔注射）可显著提高WSP和WSR品系乙醇未处理雄性小鼠对戊四氮的惊厥阈值。总体而言，WSP小鼠比WSR小鼠对3α,5α-P的抗惊厥作用更敏感。随后对暴露于乙醇蒸气或空气中24小时的雄性WSP小鼠进行的研究表明，在乙醇戒断期间，它们对3α,5α-P（0.5 - 20毫克/千克腹腔注射）的抗惊厥作用敏感性增强。只有最高剂量对暴露于空气中的动物的HICs有影响，而两个最高剂量均显著降低了暴露于乙醇中的小鼠的HICs。这些结果首次证明3α,5α-P可减轻乙醇戒断惊厥，并表明从乙醇依赖中戒断的动物对3α,5α-P的抗惊厥作用敏感性增强。
