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Item does not contain fulltext, In the first experiment, the relationship between the phase of the estrous cycle and the number of spontaneously occurring spike-wave discharges was investigated 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 emerged for the number of spike-wave discharges: a nadir during the first hours 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 enhances spike-wave discharges. There was no difference in the first few hours of the light period in the number of spike-wave discharges between proestrus and the three other days, suggesting that estradiol has no effect on spike-wave discharges. In the second study, the effects of the systemic administration of progesterone and 17-estradiol on spike-wave discharges and spontaneous behavior were investigated. It was shown that progesterone (20 and 30 mg/kg) but not estradiol (0.17Ø1.5 mg/kg) increased the number and total duration of spike-wave discharges. On the other hand, injection of RU 38486 (10 and 30 mg/kg), an antagonist of intracellular progesterone receptors, had no effect on spike-wave discharges and did not block the stimulatory effect of progesterone. The antagonist of 17-estradiol tamoxifen (1 and 3 mg/kg) did not evoke alterations in the number or duration of spike-wave discharges. Our results indicate that progesterone aggravates spike-wave discharges, but is not mediated through intracellular receptors. Since progesterone is rapidly metabolized in the brain to the positive modulator of GABAA receptor allopregnanolone, which increases spike-wave discharges in WAG/Rij rats, it is possible that the epileptiformic eff

Item does not contain fulltext, Rats of the WAG/Rij strain are considered as a genetic model for generalised absence epilepsy. The relationship between the phase of the estrous cycle and the number of spontaneously occurring spike-wave discharges (SWDs) was investigated during the 4 days of the cycle. Vaginal smears were daily made while the EEG was recorded continuously. The phase of the estrous cycle was determined on the basis of cytological examination. There were more spike-wave discharges at pro-estrus than at the other three days, suggesting a role for ovarian hormones. A circadian pattern emerged for the number of SWDs: a minimum during the first few hours of the light and a maximum during the first few hours of the dark period. This maximum occurred at the time at which maximum progesterone plasma levels can be expected. This suggests that progesterone enhances SWDs. There was no difference in the first few hours of the light period in number of SWDs between pro-estrus and the three other days. The lack of differences suggests that estradiol has no effect on SWDs. The circadian pattern of spike-wave discharges is in temporal agreement with data on circadian fluctuations in brain concentrations of progesterone and its metabolites dihydroprogesterone and allopregnanolone. This opens the possibility that the circadian distribution of SWDs is controlled by the circadian brain concentrations of progesterone and its metabolites.