斑马鱼——一种新型电惊厥动物模型

Zebrafish——A New Animal Model for Studying Electrical Stimulation-Induced Convulsion

目的:用斑马鱼建立一种电惊厥动物模型。方法:50μA电流刺激斑马鱼,观察其惊搐反应;2 000μA电流刺激斑马鱼,观察其惊厥反应。地西泮、咪达唑仑、苯巴比妥、苯妥英、丙戊酸、琥珀酸预处理斑马鱼后,分别给予50μA和2 000μA电流刺激斑马鱼1 s,观察药物抗惊搐及惊厥作用。结果:50μA电流刺激1 s可使斑马鱼发生惊搐反应,2 000μA刺激斑马鱼可发生类似小鼠最大电休克的惊厥反应。上述抗惊厥药物均可抑制电刺激所致的惊搐反应与惊厥反应(P<0.05,P<0.01)。结论:斑马鱼可作为一种新型电惊厥模型,对于神经药理学研究和抗癫痫药筛选有积极意义。

Objective： To examine the validity of a new convulsion animal model using electrical stimulation in adult zebrafish. Methods： Adult zebrafish were randomly divided into subgroups （n=10 per group） and exposed to electric current （either 50 μA or 2 000 μA） for 1 second. In order to investigate the effects of antiepileptic drugs （AEDs） on such animal model, adult zebrafish were pretreated with one of the following AEDs： diazepam, midazolam, phenobarbital, phenytoin, valproate and succinate, respectively, prior to delivering electrical stimulation. Results： The behavior profile during weak electrical stimulation （50 μA, 1 s） was characterized by scared twitch reaction, including forward channeling, jumping, swinging and circle swimming. The behavior profile during strong electrical stimulation （2 000 μA, 1 s） was characterized by convulsive reaction, being tonic, motionless, followed by rollover, coma or even death, similar to the phenotype seen in mice convulsion model using maximal electrical shocks.All the above-mentioned AEDs significantly suppressed scared twitch reaction and convulsion behavior, caused by electrical stimulation （P〈0.05 and P〈0.01 respectively）. Conclusion： This is the first report on electrical stimulation-induced convulsion in adult zebrafish. Our study provides behavioral evidence in support of adult zebrafish as a valid animal model for neuropharmacological research and potential method for antiepileptics screening.