Effects of antiepileptic drugs on 4-aminopyridine-induced epileptiform activity in young and adult rat hippocampus

Abstract

Extracellular field potential recordings were used to study the effects of the antiepileptic drugs (AEDs) carbamazepine (CBZ), phenytoin (PHT), phenobarbital (PhB) and valproic acid (VPA) on the epileptiform activity evoked by 4-aminopyridine (4-AP, 50 μM) in the CA3 subfield of rat hippocampal slices obtained from young (8–23-day-old) and adult (> 60-day-old) male rats. Ictal (duration: 3-2 rate of occurrence: 3–12 × 10 −3 s −1) and interjetai (duration: 0.2–0.8 s; rate of occurrence: 0.2–0.8 s −1) discharges were recorded in young slices, while only interictal activity (duration: 70–90 ms; rate of occurrence: 0.5–0.9 s −1) discharges were observed in adult slices. In addition, in both young and adult slices 4-AP disclosed a synchronous long-lasting potential (duration and rate of occurrence: 0.6–3 s, 7–70 × 10 −3 s −1 and 260–660 ms, 8–60 × 10 −3 s −1, respectively) that was caused by the activation of the γ-aminobutyric acid type A (GABA A) receptor. In young slices, ictal discharges were blocked by CBZ (0.05 mM), PHT (0.1 mM), PhB (0.5 mM) and VPA (0.5 mM). With the exception of PhB, higher concentrations were necessary in these experiments for blocking the interictal activity (i.e., CBZ: 0.1 mM; PHT: > 0.2 mM; VPA: 2 mM). At these concentrations, none of the AEDs blocked the interictal activity in the adult hippocampus, but only reduced the rate of occurrence. PhB enhanced the rate of occurrence of the synchronous GABA-mediated long-lasting potentials both in young (increase: 190%) and in adult (increase: 145%) slices, while VPA increased their occurrence by 54% only in young slices. CBZ decreased the rate of occurrence of this long-lasting potential only in adult hippocampus. Our data indicate that the effects of the AEDs on 4-AP-induced epileptiform discharges are both pattern- and age-dependent. The rank order of potencies of the four AEDs was: (a) in young: CBZ > PHT > PhB > VPA; (b) in adult: CBZ > PhB > PHT > VPA.