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

Abstract

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.