The ovarian hormones and absence epilepsy: a long-term EEG study and pharmacological effects in a genetic absence epilepsy model

In the first experiment, the relationship between the phase of the estrous cycle and the number of spontaneously occurring spike-wave discharges was i nvestigated in WAG/Rij rats, a model for generalized absence epilepsy. The electroencephalogram (EEG) was continuously recorded for 96 h in eight rats chronically equipped with cortical EEG electrodes. A circadian pattern eme rged for the number of spike-wave discharges: a nadir during the first hour s of the light period, and an acrophase during the first hours of the dark period. This daily maximum was increased at proestrus day compared with the other days of the cycle, when the plasma level of progesterone is enhanced specifically at these hours of this day. This suggests that progesterone e nhances spike-wave discharges. There was no difference in the first few hou rs of the light period in the number of spike-wave discharges between proes trus and the three other days, suggesting that estradiol has no effect on s pike-wave discharges. In the second study, the effects of the systemic admi nistration of progesterone and 17 beta -estradiol on spike-wave discharges and spontaneous behavior were investigated. It was shown that progesterone (20 and 30 mg/kg) but not estradiol (0.17-1.5 mg/kg) increased the number a nd total duration of spike-wave discharges. On the other hand, injection of RU 38486 (10 and 30 mg/kg), an antagonist of intracellular progesterone re ceptors, had no effect on spike-wave discharges and did not block the stimu latory effect of progesterone. The antagonist of 17 beta -estradiol tamoxif en (1 and 3 mg/kg) did not evoke alterations in the number or duration of s pike-wave discharges. Our results indicate that progesterone aggravates spi ke-wave discharges, but is riot mediated through intracellular receptors. S ince progesterone is rapidly metabolized in the brain to the positive modul ator of GABA(A) receptor allopregnanolone, which increases spike-wave disch arges in WAG/Rij rats, it is possible that the epileptiformic effects of pr ogesterone are mediated through this metabolite. (C) 2001 Elsevier Science B.V. All rights reserved.