Phenytoin's effect on the spread of seizure activity in the amygdala kindling model

Phenytoin is a major antiepileptic drug for treatment of limbic seizures. The effect of phenytoin on the generation and spread of seizure activity was studied in a rat model of this type of seizures. Sprague-Dawley and Wistar rats were implanted with a stimulation and recording electrode in the basolateral amygdala. Naive Sprague-Dawley rats showed an increase in current intensity necessary for eliciting afterdischarges (afterdischarge threshold) of about 200% after administration of phenytoin (75 mg/kg i.p.), while seizure severity at threshold was increased compared to controls. Afterdischarge and seizure durations were significantly prolonged under phenytoin. This result suggests that phenytoin can exert a potent anticonvulsant effect on the generation of focal seizure activity, but it does not suppress or may even increase ongoing afterdischarge activity once it occurs. Following amygdala kindling in Wistar rats, administration of phenytoin again resulted in an increase in the afterdischarge threshold. However, all rats still showed generalized seizures, and epileptic afterdischarges could be recorded in various limbic brain regions at threshold current. This result suggests that phenytoin can increase the threshold for generation of epileptic discharges in kindled rats, but is not able to prevent the development of generalized seizure activity and the spread of afterdischarges within the limbic system when focal activity is initiated. We conclude that phenytoin is able to suppress focal seizure activity in the amygdala kindling model of the rat. However, it does not prevent the spread of seizure activity originating in the limbic system. Therefore, a decrease in focal seizure susceptibility seems to be the primary target for phenytoin's anticonvulsant action.