Previous developmental studies in vitro suggested that the inhibitory
neurotransmitter GABA exerts depolarizing and excitatory actions on the immature neurons and that depolarizing
GABA is causally linked to ictal activity during the first weeks of postnatal life. However, remarkably little is known on the role of
GABA in the generation of neonatal
seizures in vivo. Here, using extracellular recordings from CA3 hippocampus, we studied the effects of
GABA(A)-acting drugs on electrographic
seizures induced by local intrahippocampal injection of the epileptogenic agents (high K(+)/low Mg(2+)) in the nonanesthetized rats in vivo and in the hippocampal slices in vitro during the second postnatal week (postnatal days P8-12). We found that in vivo, the induction of ictal-like events was facilitated by co-infusion of high-K(+)/low Mg(2+) together with the
GABA(A) antagonist
bicuculline or
gabazine. Moreover, the infusion of
bicuculline alone caused ictal-like activity in approximately 30% of cases. Co-infusion of the
GABA(A) receptor agonist isoguvacine or the
GABA(A)-positive allosteric modulator
diazepam completely prevented high-K(+)/low Mg(2+)-induced
seizures. In in vitro studies using hippocampal slices, we also found that high-K(+)/low Mg(2+) produced ictal activity that was exacerbated by
bicuculline and
gabazine and reduced by
isoguvacine. Thus in the model of high-K(+)/low Mg(2+)-induced
seizures both in in vivo and in vitro conditions,
GABA, acting via
GABA(A) receptors, has an
anticonvulsant effect during the critical developmental period of enhanced excitability.