Validation of the Zebra-fish Pentylene Tetrazol Seizure Model: Behaviour Assay for Assessing Anti-Epileptic Drug Efficacy

The availability of zebra-fish larvae model of epileptic seizure provides opportunities to identify novel anticonvulsants for treatment of people with epilepsy. However, the major parameters of zebra-fish behavior assay for assessing antiepileptic drug efficacy existed disparity, which resulted in different results in previous studies. In this study, we chose the high, medium, slow-speed moved distances and the total distances moved for seizure-like activity quantification in individual wells of a 48-well plate in the dark phase and used this zebra-fish seizure model to assess three commonly prescribed anti-epileptic drug’s efficacy and screen bioactive components from plant extract. Results showed that the high-speed moved distances were given a more reasonable and sensitive dose-response curve than the total distances in zebra-fish larvae model exposed to 10 mM pentylene tetrazole. Besides, we also optimized the vehicle (dimethyl sulfoxide, DMSO) concentration used in epileptic behaviour assay. The three anti-epileptic drugs, phenytoin, valproate sodium and carbamazepine showed the same efficacy patterns in zebra-fish seizure model as in mammalian epileptic models. We also found four positive hits from plant (Vaccinium spp.) extract in primary drug screening, two hits exhibited concentration-dependent inhibition of locomotor activity, confirming their anticonvulsant characteristics. These results indicated that this zebra-fish larvae model could be useful for assessing anti-epileptic drug efficacy, facilitating the primary drug screening and evaluating of effective components in medicinal plants. Validation of the Zebra-fish Pentylene Tetrazol Seizure Model: Behaviour Assay for Assessing Anti-Epileptic Drug Efficacy Chongbin Liu1,2*, Juan Zhou1, Yong Zhang2, Taotao Zhu2, Rui Wang1 and Chunqi Li2,3 1Department of Physiology, Huzhou University, Huzhou, Zhejiang Province 313000, P. R. China 2Zhejiang Provincial Key Lab for Technology and Application of Model Organisms, Wenzhou Medical University, Wenzhou, Zhejiang Province 325035, P. R. China 3Hunter Biotechnology, Inc., Transfarland, Hangzhou, Zhejiang Province 311231, P. R. China