Mhatre M C, Gonzalez L P
Department of Psychiatry & Behavioral Sciences, University of Oklahoma Health Sciences Center, Oklahoma City 73190-3000, USA.
Pharmacol Biochem Behav. 1999 May;63(1):93-9. doi: 10.1016/s0091-3057(98)00257-3.
Clinical research into the etiology of ethanol withdrawal seizures has shown an increase in the number and severity of seizures with increasing numbers of withdrawal episodes. The aim of the present study was to determine the effects of multiple ethanol withdrawals on the seizure sensitivity to the GABA(A) receptor inverse agonist Ro15-4513. In this study, three groups of laboratory rats received varying amounts of either continuous or intermittent ethanol exposure. A fourth group (Naive) received no ethanol exposure. Eight hours following the last withdrawal from chronic ethanol exposure, animals were tested for sensitivity to Ro15-4513-induced motor convulsions. Seizure sensitivity was significantly increased in all ethanol-treated groups compared to ethanol-naive controls, which did not exhibit any convulsive responses to this dose of Ro15-4513. Furthermore, rats exposed to multiple ethanol withdrawals exhibited significantly higher sensitivity to drug-induced seizures than did animals experiencing only a single ethanol withdrawal. Although the specific mechanism of this enhanced convulsant effect of Ro15-4513 following multiple ethanol withdrawals remains to be determined, these results suggest an involvement of GABA(A)-benzodiazepine receptors in this multiple withdrawal phenomenon.
关于乙醇戒断性癫痫病因的临床研究表明，随着戒断发作次数的增加，癫痫发作的数量和严重程度也会增加。本研究的目的是确定多次乙醇戒断对癫痫发作对GABA(A)受体反向激动剂Ro15 - 4513敏感性的影响。在本研究中，三组实验大鼠接受了不同剂量的连续或间歇性乙醇暴露。第四组（未处理组）未接受乙醇暴露。在最后一次从慢性乙醇暴露中戒断8小时后，测试动物对Ro15 - 4513诱导的运动性惊厥的敏感性。与未接触乙醇的对照组相比，所有乙醇处理组的癫痫发作敏感性均显著增加，对照组对该剂量的Ro15 - 4513未表现出任何惊厥反应。此外，经历多次乙醇戒断的大鼠对药物诱导的癫痫发作的敏感性显著高于仅经历一次乙醇戒断的动物。尽管多次乙醇戒断后Ro15 - 4513这种增强的惊厥作用的具体机制仍有待确定，但这些结果表明GABA(A)-苯二氮䓬受体参与了这种多次戒断现象。
