Gonadal status-dependent effects of in vivo β-estradiol administration to female rats on in vitro epileptiform activity induced by low [Mg2+]o in combined hippocampus-entorhinal cortex slices

•Seizure modulating effects of estradiol in female rats depend on gonadal status.•Estradiol delays epileptiform activity within the dentate gyrus network.•Estradiol promotes epileptiform discharges in brain slices from intact female rats.

SummaryThere are controversial data regarding estrogen effects on neuronal excitability. We investigated whether β-estradiol (EB) administration to ovariectomized (OVX) or gonadally intact female rats alters epileptiform activity within the dentate gyrus network induced in vitro by removing [Mg2+]o in combined hippocampus-entorhinal cortex slices. In vivo EB administration significantly influenced the epileptiform activity in gonadal status-dependent manner. The onset of epileptiform discharges was modestly delayed in slices from OVX rats replaced with physiologically relevant doses of EB but the number of discharges was not affected. In contrast, EB administration to gonadally intact rats had robust effects such that: EB delayed the onset of discharges but significantly increased their number within the dentate gyrus network. Our data suggest that EB in physiologically relevant concentrations does not seem to negatively affect hippocampal neuronal excitability, nevertheless supraphysiological EB levels may enhance seizure severity.