Finasteride blocks the reduction in ictal activity produced by exogenous estrous cyclicity

The purpose of the present study was to examine seizure activity during reduced 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha,5 alpha-THP) production. Ovariectomized Long-Evans rats were stereotaxically implanted with bipolar electrodes above the perforant pathway; silastic implants filled with estradiol-17-benzoate (EB) and progesterone were inserted subcutaneously to mimic diestrus, Estrus was then induced in half of these animals by injection of EB (30 mu g) and progesterone (2.5 mg), 48 and 4 h, respectively, prior to perforant pathway stimulation, Half of the estrous and diestrous rats also received a 5 alpha-reductase inhibitor, finasteride (50 mg/kg), 6 h prior to perforant pathway stimulation, The estrous condition was associated with reduced number and duration of partial seizures, improved performance on a Morris water maze recovery of function test, reduced neuronal loss in the hilar region of the hippocampus, and elevated central and plasma 3 alpha,5 alpha-THP, compared to estrus + finasteride, diestrus + vehicle and diestrus + finasteride conditions, which did not differ from each another. These data suggest antiseizure effects of estrus may be caused, in part, by the action of 3 alpha,5 alpha-THP and that the precipitous decline in 3 alpha,5 alpha-THP may restore seizure threshold to control levels.