A Zebrafish Behavior Assay for Assessing Anti- Epileptic Drug Efficacy

ABSTRACT


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 antiepileptic drug efficacy existed disparity. 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.
Results also 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 (PTZ). Moreover, this
seizure-like swimming pattern was alleviated by the addition of either phenytoin (PHT) or valproate sodium (VPA),
two commonly prescribed anti-epileptic drugs (AEDs). They exhibited concentration-dependent inhibition of both
locomotor activity and PTZ-induced c-fos transcription, confirming their anticonvulsant characteristics. Whereas
carbamazepine (CBZ) promoted zebrafish larvae movement by 26% at 30 μM and 116.7% at 100 μM, and sharply
suppressed zebrafish larvae motility about 94.8% at 300 μM. C-fos expression significantly decreased at 30 μM and
300 μM CBZ, which was found to oppose various aspects of the PTZ-induced changes in activity. These results indicated
that this zebrafish larvae model could be useful for studying drug efficacy, predicting drug targets and aiding our
understanding of disease etiology.