氯硝西泮抗大鼠听源惊厥耐受性的受体学基础

以听源惊厥大鼠为模型，观察了给予氯硝西泮１ｗｋ及６ｗｋ后，其对听源惊厥大鼠的抗惊作用及抗惊耐受性，同时通过对大鼠脑组织ＧＡＢＡＡ受体的检测，对其抗惊作用耐受性机制进行了研究。结果显示：氯硝西泮对听源惊厥大鼠有明显的抗惊作用，但长期应用可产生耐受性，表现为惊厥等级的升高。模型大鼠的溶剂对照组较正常Ｗｉｓｔａｒ大鼠ＧＡＢＡＡ－受体的Ｂｍａｘ明显降低，给予氯硝西泮可明显增加Ｂｍａｘ；但长期给予则Ｂｍａｘ又降低。提示：氯硝西泮抗大鼠听源惊厥耐受性与ＧＡＢＡＡ－受体下调有关。

Receptor base on tolerance of the antiepileptic effect to clonazepam in the audiogenic seizure rats

Combining the observation of rat behavior with the [3 H] muscimol radioligand binding experiment,the mechanisms of CZPantiepileptic effect and tolerance were studied.The audiogenic seizure rats were used,and divided into vehicle control,short time CZP-prertreated,and long time CZP-pretreated group.The results showed that(1)the bell-stimulation made control rats convulsion,(2)short timeCZP pretreated rats showed no response to bell;(3)long time-CZP pretreated rats resembled with the control rats;(4)in the short time-CZPPretreated groups,the Bmax binding to GABAAreceptor were highter than in the control groups Significantly, but the Bmax binding to GABAA-reCeptor did not show significant differences between the control and long-time-CZP pretreated group.The results suggested that CZP inhibited the convulsion of audiogenic seizure rats signifiCantly,and raised the Bma x to GABAA-receptor.But long time CZP group lost the antiepileptic effects and the Bmax binding to GABAA-recePtor were diminished markedly.