Progesterone and testosterone modulate the convulsant actions of pentylenetetrazol and strychnine in mice

The influence of progesterone and testosterone on the incidence of seizures after administration of intraperitoneal pentylenetetrazol and subcutaneous strychnine was evaluated in mice. Pentylenetetrazol and strychnine were ad ministered in doses that induced seizures in 40-50% of control mice in dioe strus (48 and 0.9 mg/kg, respectively). The percentage of seizures induced by pentylenetetrazol and strychnine was significantly lower in female mice in prooestrus/oestrus, when progesterone levels are high, than in dioestrus , when progesterone levels are low. Pretreatment of pentylenetetrazol-chall enged mice with progesterone (250 mu g/kg) increased the incidence of seizu res in prooestrus/oestrus, without affecting seizures in dioestrus. The sam e pretreatment in strychnine-challenged mice also increased the incidence o f seizures in prooestrus-dioestrus. but significantly reduced the incidence of seizures in dioestrus. In addition, progesterone pretreatment significa ntly increased the percentage of deaths induced by strychnine in prooestrus -oestrus, reducing deaths in dioestrus. Orchidectomized male mice had a sig nificantly higher incidence of seizures after administration of pentylenete trazol and strychnine than control mice. Administration of 11 daily doses o f 250 mu g/kg of testosterone to castrated mice significantly reduced the i ncidence of seizures induced by pentylenetetrazol. These results confirm th e modulatory influence of reproductive steroids on the excitability of the central nervous system and the possible clinical importance of progesterone and testosterone in the management of partial epilepsy.