Differential regulation of seizure activity in the hippocampus of male and female rats

OBJECTIVE: The aim of the current study was to directly examine and compare the susceptibility to N-methyl-D-aspartate-induced seizures in male versus female rats. We Also sought to compare the anticonvulsant effects of magnesium sulfate in these two groups. STUDY DESIGN: Eighteen female and 10 male rats were stereotaxically implanted with a chronic bipolar recording electrode in the hippocampus and an injection cannula in the lateral cerebral ventricle. After 1 week rats randomly received an intravenous injection of 90 mg/kg magnesium sulfate or saline solution control. Fifteen minutes after the infusion rats were given the convulsant N-methyl-D-aspartate at a dose of 5 μg/μl by direct intraventricular injection. Electrical seizure activity was thereafter assessed for 20 minutes. All data were analyzed by the Mann-Whitney U test and Student t test. RESULTS: In saline solution-treated rats receiving the convulsant N-methyl-D-aspartate, females had significantly lower total duration (p< 0.01) and total number of seizures (p< 0.05) compared with the male rats. The initial seizure was not affected by gender. In the female animals magnesium sulfate significantly reduced first seizure duration (p< 0.01) compared with saline solution controls. In males magnesium sulfate reduced both total duration (p< 0.05) and total seizure number (p< 0.05) compared with saline solution-treated animals. CONCLUSION: N-methyl-D-aspartate-induced seizure activity is more severe in males versus female rats. Magnesium sulfateʹs effect on N-methyl-D-aspartate-induced seizures is also dependent on gender. We speculate that seizure regulation may be hormonally influenced.