Effects of standard anticonvulsant drugs on different patterns of epileptiform discharges induced by 4-aminopyridine in combined entorhinal cortex–hippocampal slices

Abstract

Application of 4-aminopyridine (4-AP) has previously been reported to produce different patterns of epileptiform discharges in entorhinal cortex (EC)–hippocampal slices: recurrent short discharges (RSDs) in hippocampal area CA1, seizure-like events (SLEs) and negative-going potentials (NGPs) in the medial entorhinal cortex (mEC). Using recordings of field potentials, we investigated the pharmacological effects of the clinically employed standard anticonvulsant drugs phenytoin (PHT), carbamazepine (CBZ), valproic acid (VPA) and phenobarbital (PHB) and those of pentobarbital (PB) on 4-AP-induced epileptiform activity. The anticonvulsant drugs showed different effects: SLEs were completely blocked by all tested drugs. Valproic acid, which suppressed all epileptiform activities, seemed to have the most fundamental effect of all drugs on 4-AP induced activity, because under phenytoin and carbamazepine, some epileptiform activity was still observable. The RSDs in hippocampal area CA1 of the hippocampus did not respond to the different anticonvulsants. In contrast, PB decreased the frequency of the RSDs in CA1 and enhanced the frequency of the NGPs in the EC. We propose that the activities induced by 4-AP in the combined entorhinal cortex–hippocampal slices may provide an in vitro model for the development of new drugs against difficult-to-treat focal epilepsy.