Sex differences in models of temporal lobe epilepsy: role of testosterone

Kainic acid and pilocarpine were used to assess sex differences in temporal lobe seizures. Adult Sprague-Dawley rats were injected with kainic acid (10-12 mg/kg) or with pilocarpine (380 mg/kg) and behavior was recorded for the next 3 h. Trunk blood was collected for hormonal measurements. Our data indicate that the male is more susceptible to the convulsant effects of agents that produce temporal lobe-like seizures. Males presented a higher amount of full limbic convulsions than females. To assess the role of plasma testosterone levels in kainate-induced seizures, a group of males was gonadectomized and half received testosterone replacement. The presence of testosterone, in intact and in gonadectomized males with testosterone replacement, increased the susceptibility to seizure. Seizures were either stronger (full limbic) or more frequent in animals with testosterone compared to animals devoid of testosterone. These results suggest that differences in plasma levels of testosterone may be partially responsible for the observed gender differences in seizure susceptibility. Our data reveal a reciprocal relationship between kainic acid-induced temporal lobe seizures and plasma testosterone. Testosterone enhances the occurrence and the severity of seizures. Conversely, kainic-acid-induced seizures decrease plasma testosterone. The higher plasma corticosterone levels found in these males suggest that kainic acid-induced seizures activate the hypothalamic-pituitary-adrenal axis which may induce alterations in plasma levels of male reproductive hormones.