Effect of Neurosteroid Withdrawal on Spontaneous Recurrent Seizures in a Rat Model of Catamenial Epilepsy

Abstract

Women with epilepsy often report an increase in seizures at the time of menstruation, a condition referred to as catamenial epilepsy. Perimenstrual seizure exacerbation has long been known to be associated with an abrupt withdrawal of progesterone. The progesterone’s antiseizure effect is due in part to its conversion to the “neurosteroid” allopregnanolone. However, there is no specific animal model of catamenial epilepsy. In this study, we sought to develop a rat model of catamenial seizure exacerbation based on the premise that allopregnanolone withdrawal leads to the exacerbation of spontaneous seizures in epileptic state. Chronic epilepsy was induced in rats by treatment with pilocarpine. Rats were monitored for spontaneous seizures during 2–6 months post pilocarpine. EEG was recorded from hippocampus and cortex. Pilocarpine treatment was associated spontaneous seizures after latency of 60 days post pilocarpine. The average seizure frequency was 15 seizures per week. At 5 months post pilocarpine, majority of rats exhibited bilateral neurodegeneration and a robust aberrant mossy fiber sprouting. To model catamenial seizure exacerbation, epileptic rats were subjected to repeated neurosteroid withdrawal by a pseudopregnancy-finasteride paradigm. Neurosteroid withdrawal showed a tendency of increased seizure frequency, including exacerbation of EEG discharges. Thus, this neurosteroid withdrawal paradigm in epileptic rats may provide a suitable animal model of catamenial seizure exacerbation for use in testing novel agents. ∗∗ Supported by NIH/NINDS grant NS052158 ∗∗