Treatment with the antiepileptic drugs phenytoin and gabapentin ameliorates seizure and paralysis of Drosophila bang-sensitive mutants

Drosophila bang-sensitive (bs) mutants exhibit a stereotypic seizure and paralysis following exposure to mechanical shock. In a physiological preparation, seizures and failures corresponding to the defective behavior are observed in response to high frequency stimulation. The amplitude of the stimulus necessary to produce bs behavior, or seizure threshold, varies with bs mutant and its gene dosage. In many respects, the bs defects are similar to those observed in mammalian seizure disorders. Antiepileptic drugs (AEDs) were administered by feeding to easily shocked(2) (eas(2)), a representative bs mutant. The mean recovery times of treated flies were examined in comparison to control cultures. Some of the drugs administered, including carbamazeprine, ethosuximide, and vigabactrin, had little or no effect on the bs behavior of eas(2). Gabapentin, however, showed a reduction in mean recovery time with chronic drug exposure. Phenytoin also had a significant effect on the bs behavior of treated flies. There was a reduction of both mean recovery time and the percentage of flies that displayed bang-sensitive behavior with both acute and chronic treatment. The adult giant fiber preparation was used to examine the effects of phenytoin physiologically. Treated eas(2) flies showed changes in their response to normal stimulation as well as alterations in seizure threshold in response to high frequency stimulation. Gabapentin was also effective against two other bs mutants, bangsenseless(1) and slamdance(iso7.8), at strain-specific concentrations, while phenytoin also reduced bang-sensitive behaviors in bangsenseless(1) in a dose dependent manner. AEDs, therefore, can be used to dissect aspects of bs behavior and this model may be useful in understanding the underlying basis of seizure disorders.