Many women with epilepsy experience an increase in the frequency of seizures around the time of menstruation. Catamenial seizures are difficult to control and, thus, pose a significant clinical problem. A decrease in seizure frequency has been reported to occur during the luteal phase of the menstrual cycle, a time when progesterone reaches its highest blood levels. This and other observations have led to the suggestion that progesterone has anticonvulsant activity. Estrogen, on the other hand, has been hypothesized to have convulsant or """"""""proconvulsant"""""""" properties. Presently, the means by which gonadal steroids modulate epileptiform activity are not well understood. The overall goal of this proposal is to investigate the anticonvulsant properties of progesterone, and the antiestrogen, clomiphene citrate. Using the in vitro hippocampal slice as a model and the techniques of extracellular and interacellular neurophysiological recording, we will investigate the direct effects of progesterone, a progesterone metabolite, and clomiphene citrate on an epileptogenic focus. Specifically, we will determine if these substances suppress epileptiform activity in the hippocampal slice. In addition, if we confirm that progesterone or clomiphene citrate modulate epileptiform activity in the slice, we will investigate some of the cellular mechanisms by which they may influence neuronal excitability. These experiments will provide us with information about how gonadal steroids influence epileptiform activity. It is hoped that the information derived from these and future studies will contribute to a better understanding of catamenial seizures and eventually, to the development of improved methods to treat this disorder.
