Region-specific modulation of limbic seizure susceptibility by ovarian steroids

Gonadal steroid hormones can markedly affect seizure susceptibility. Ovario hysterectomized female rats given ovarian steroid hormone supplements were used to evaluate the effects of ovarian steroids on epileptiform activity i n hippocampal slices in vitro and on flurothyl-induced seizures in vivo. Se izure susceptibility was compared in the entorhinal cortex (EC) and CA1 reg ions of the hippocampus perfused with Mg2+-free medium, which leads to epil eptiform discharges caused by a relief of voltage-dependent NMDA receptor b lock. After in vivo treatment with 500 mu g of progesterone for 2 h prior t o slice preparation, the latency to onset of low Mg2+-induced epileptiform activity of slices was significantly prolonged compared to slices from cont rols. In contrast, progesterone replacement accelerated the development of epileptiform activity in the CAL region, Neither estrogen alone (2 x 2 mu g of estradiol benzoate, 48 and 24 h prior to the experiment), nor a combine d treatment with estrogen plus progesterone, significantly affected seizure susceptibility in either CAI or the EC. There were no consistent effects o f estrogen or progesterone, alone or in combination, on flurothyl-induced s eizures in vivo. The data suggest that in vitro, progesterone alters seizur e susceptibility in a site and seizure model-specific fashion. The differen tial effects of progesterone may be due to differential expression of proge sterone receptor isoforms or metabolites in specific brain areas suggesting that selective modulation of NMDA receptor-dependent epileptiform activity may play a role in hormonal effects on epileptogenesis. (C) 1999 Elsevier Science B.V. All rights reserved.