Antiepileptic drugs abolish ictal but not interictal epileptiform discharges in vitro

Purpose: We established the effects of the antiepilepticdrugs (AEDs) carbamazepine (CBZ), topiramate(TPM), and valproic acid (VPA) on theepileptiform activity induced by 4-aminopyridine(4AP) in the rat entorhinal cortex (EC) in anin vitro brain slice preparation.Methods: Brain slices were obtained from Sprague-Dawley rats (200–250 g). Field and intracellularrecordings were made from the EC during bathapplication of 4AP (50 microM). AEDs, and in someexperiments, picrotoxin were bath applied concomitantly.Results: Prolonged (>3 s), ictal-like epileptiformevents were abolished by CBZ (50 microM), TPM(50 microM), and VPA (1 mM), whereas shorter (<3 s)interictal-like discharges continued to occur, evenat concentrations up to 4-fold as high. gamma-Aminobutyricacid (GABA)A–receptor antagonism changedthe 4AP-induced activity into recurrent interictallikeevents that were not affected by CBZ or TPM,even at the highest concentrations. To establishwhether these findings reflected the temporal featuresof the epileptiform discharges, we testedCBZ and TPM on 4AP-induced epileptiform activitydriven by stimuli delivered at 100-, 10-, and 5-sintervals; these AEDs reduced ictal-like responsesto stimuli at 100-s intervals at nearly therapeuticconcentrations, but did not influence shorter interictal-like events elicited by stimuli deliveredevery 10 or 5 s.Conclusions: We conclude that the AED ability tocontrol epileptiform synchronization in vitrodepends mainly on activity-dependent characteristicssuch as discharge duration. Our data are inkeeping with clinical evidence indicating that interictalactivity is unaffected by AED levels that areeffective to stop seizures.