EXTRACELLULAR MAGNESIUM AND ANTICONVULSANT EFFECTS OF VALPROATE IN YOUNG-RAT HIPPOCAMPUS

Extracellular field potential recordings were made in CA3 subfield of hippocampal slices from rats aged 11-22 days. In these experiments, we analyzed the effects induced by modifying [Mg2+] in the medium (1 or 2 mM) on (a) 4-aminopyridine (4-AP, 50 mu M)-induced synchronous event s (including ictal- and interictal-like epileptiform discharges as wel l as gamma-aminobutyric acid (GABA)-mediated potentials), and (b) the changes induced by the antiepileptic drug (AED) valproate (VPA 2 mM) o n such activities. Changing [Mg2+] from 1 to 2 mM induced age-dependen t effects consisting of reduction in rate of occurrence of ictal-like discharges at 11-13 days (55% reduction, p < 0.005) and 14-16 days (46 % reduction, p < 0.025) postpartum. At any age, the rate of occurrence and the amplitude of the GABA-mediated synchronous potentials tended to decrease in 1 mM [Mg2+], Similar effects were noted when changes in [Mg2+] were made during continuous application of the competitive ant agonist of the N-methyl-D-aspartate (NMDA) receptor DL-2-amino-5-phosp honovalerate (APV 50 mu M). AS previously reported, interictal and ict al discharges were blocked by addition of VPA to medium containing 2 m M [Mg2+]. Such an effect was not observed when [Mg2+] was decreased to 1 mM. In 1 mM, but not in 2 mM [Mg2+], VPA increased the amplitude of GABA-mediated synchronous potentials. Our results indicate that [Mg2] plays a role in modulating occurrence of 4-AP-induced ictal activity and that it can influence the effects of VPA in this in vitro model o f epileptogenesis, Because these findings are also observed in the pre sence of the NMDA receptor antagonist APV, we conclude that they are n ot mediated by a mechanism linked to the NMDA receptor-ionophore.