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 micrograms/microliters 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 sulfate's effect on N-methyl-D-aspartate-induced seizures is also dependent on gender. We speculate that seizure regulation may be hormonally influenced.