Validation of the Zebrafish Pentylenetetrazol Seizure Model: Behavior Assay for Assessing Anti-Epileptic Drug Efficacy

The availability of zebrafish larvae model of epileptic seizure provides opportunities to identify novel anticonvulsants for treatment of people with epilepsy. However, the major parameters of zebrafish behavior assay for assessing anti-epileptic 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 zebrafish seizure model to assess three commonly prescribed anti-epileptic drug’s efficacy and screen bioactive components from plant extrat. Results showed that the high-speed moved distances were given a more reasonable and sensitive dose-response curve than the total distances in zebrafish larvae model exposed to 10 mM pentylenetetrazole . Besides, we also optimized the vehicle (dimethyl sulfoxide, DMSO) concentration used in epileptic behavior assay. The three anti-epileptic drugs, phenytoin, valproate sodium and carbamazepine showed the same efficacy patterns in zebrafish 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 zebrafish larvae model could be useful for assessing anti-epileptic drug efficacy, facilitating the primary drug screening and evaluating of effective components in medicinal plants.