The zebrafish has emerged as a vertebrate model system amenable to study human disease states. Zebrafish models of human neurobiological disorders offer the opportunity to identify novel therapeutic treatments through phenotype-based chemical modifier screens and larval zebrafish have previously been suggested as an experimental model of epilepsy-related pathogenic states.
Using alternating light and dark conditions, combined with a sub-convulsive concentration of pentylenetetrazole (PTZ) we show that the most pronounced effects were obtained with the neurosteroids alfaxalone and allopregnanolone. In addition, neurosteroid and benzodiazepine drug combinations were found to significantly improve phenotypic rescue in larval zebrafish, as reflected by a reduction in the minimal effective drug concentrations needed to reverse locomotion in the alternating light/dark assay.