Effects of d-amphetamine and apomorphine in a new animal model of petit mal epilepsy

Abstract

d-Amphetamine is effective in controlling seizures in petit mal epilepsy. The flash-evoked afterdis-charge (FEAD) in rats has been proposed as a model of the peit mal seizure. The experiments reported here investigated the dose response relationship for the suppression of FEAD by d-amphetamine, and compared its effects with those of the dopamine-mimetic, apomorphine. Significant suppression of FEAD was observed at doses of d-amphetamine greater than 0.2 mg/kg. A maximum decrease of 60% occurred at 1.2 mg/kg. Higher doses did not result in any further suppression. In contrast, apomorphine and no effect on the FEAD even at doses that induced intense stereotypic behavior. In other experiments, administration of either the dopamine antagonist pimozide or the alpha-adrenergic antagonist phenoxybenzamine exacerbated FEAD and also prevented the suppression of FEAD by d-amphetamine. The results of these experiments support the hypothesis that the FEAD is a valid model of the petit mal seizure. Furthermore, they provide evidence that norepinephrine is necessary for the seizure-suppressant action of d-amphetamine.