MAGNESIUM-SULFATE REDUCES SEIZURES INDUCED BY CENTRAL ADMINISTRATION OF THE EXCITATORY AMINO-ACID N-METHYL-D-ASPARTATE IN RATS

N-Methyl-D-aspartate (NMDA) has been implicated in a number of pathoph ysiologic conditions, including seizures. Magnesium is a physiologic b locker of the NMDA receptor. As magnesium sulfate (MgSO4) is currently used as a treatment for eclamptic seizures in North America, we exami ned the anticonvulsant effects of MgSO4 on central NMDA-induced seizur es. Forty-one female rats were surgically anesthetized and a bipolar r ecording electrode was stereotaxically implanted into the dorsal hippo campus, while a cannula was implanted into the lateral cerebral ventri cle for drug injection. Following 1-week recovery, baseline behavior a nd electrical activity were recorded. Two treatment protocols were exa mined: (a) chronic-intraperitoneal injection of 270 mg/kg MgSO4, follo wed 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 mu 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) MgSO4. Total seizure number was significantly reduced in the chronic MgSO4 g roup (P < 0.05). Total seizure duration was significantly reduced in b oth the chronic (P < 0.05) and acute (P < 0.05) MgSO4 groups. Mortalit y was 30% in the chronic control group, whereas none of the rats that received chronic MgSO4 died. We conclude that magnesium sulfate reduce s seizure activity induced by centrally administered NMDA. These resul ts support our previous observations that magnesium does have central anticonvulsant effects.