Magnesium Sulfate Reduces Seizures Induced by Central Administration of the Excitatory Amino Acid N-Methyl-D-Aspartate in Rats

Abstract

A'-Methyl-D-aspartate (NMDA) has been implicated in a number of pathophysiologic conditions, including seizures. Magnesium is a physiologic blocker of the NMDA receptor. As magnesium sulfate (MgSO₄) is currently used as a treatment for eclamptic seizures in North America, we examined the anticonvulsant effects of MgSO₄ on central NMDA-induced seizures. Forty-one female rats were surgically anesthetized and a bipolar recording electrode was stereotaxically implanted into the dorsal hippocampus, while a cannula was implanted into the lateral cerebral ventricle for drug injection. Following 1-week recovery, baseline behavior and electrical activity were recorded. Two treatment protocols were examined: (a) chronic–intraperitoneal injection of 270 mg/kg MgSO₄, followed every 20 min with 27 mg/kg MgSO₄ for a total of 2 h; and (b) acute—intravenous injection of MgSO₄ (30, 60, or 90 mg/kg) in a volume of 1.5 mL/kg via the tail vein. Following either treatment protocol, rats received 1 µ;L of 20 mg/mL NMDA via the cannula, and seizure activity was assessed. Onset to the first seizure was significantly lengthened in rats receiving both chronic (P < 0.01) and acute (P < 0.01) MgS0₄. Total seizure number was significantly reduced in the chronic MgSO₄ group (P < 0.05). Total seizure duration was significantly reduced in both the chronic (P < 0.05) and acute (P < 0.05) MgSO₄ groups. Mortality was 30% in the chronic control group, whereas none of the rats that received chronic MgSO₄ died. We conclude that magnesium sulfate reduces seizure activity induced by centrally administered NMDA. These results support our previous observations that magnesium does have central anticonvulsant effects.

Key Words:

• Eclampsia
• Excitatory amino acids
• Magnesium
• Seizures