Estradiol facilitates kainic acid-induced, but not flurothyl-induced, behavioral seizure activity in adult female rats

Purpose: This study was designed to determine whether previously demonstrat ed increases in hippocampal axospinous synapse density and NMDA receptor fu nction induced by estradiol are paralleled by increased susceptibility to l imbic (kainic acid induced) or generalized (flurothyl induced) behavioral s eizures. Methods: Kainic acid was injected systemically to ovariectomized adult fema le rats treated with either estradiol or oil vehicle. The latencies to each of five stages of seizure-related behaviors (staring, wet-dog shakes, head waving and chewing, forelimb clonus. rearing, and falling) were recorded f or each animal. Flurothyl was administered by inhalation to ovariectomized adult female rats treated with estradiol alone, estradiol followed by short -term progesterone, or oil vehicle. The latencies to each of three stages o f seizure-related behaviors (first myoclonic jerk, forelimb clonus, wild ru nning and bouncing) were recorded for each animal. Results: Estradiol treatment decreased the latency to seizure-related behav iors induced by kainic acid, but neither estradiol alone nor estradiol foll owed by progesterone had any effect on flurothyl-induced seizure-related be haviors. Conclusions: The same estradiol treatment paradigm known to induce structur al and functional changes in the excitatory circuitry of the hippocampus fa cilitates the progression of kainic acid-induced seizures, which are known to involve the hippocampus, but has no effect on flurothyl-induced seizures . The lack of an effect of estradiol alone or estradiol followed by progest erone on flurothyl-induced seizures indicates that estradiol's effects on s eizure susceptibility do not result from increased neuronal excitability th roughout the brain, but rather involve action within the limbic system. The data suggest that structural and functional changes in hippocampal circuit ry induced by estradiol may contribute to increased susceptibility to limbi c seizure activity.