Effect of magnesium sulfate on excitatory amino acid receptors in the rat brain: I. N-methyl-D-aspartate receptor channel complex

OBJECTIVE: Our purpose was to determine the effect of peripherally administered magnesium sulfate on the N-methyl-D-aspartate receptor channel complex in the rat central nervous system. STUDY DESIGN: Six rats were injected intraperitoneally with 270 mg/kg magnesium sulfate, followed by 27 mg/kg every 20 minutes for 4 hours. Controls (n = 6) received saline solution. Six rats received intraperitoneal injections of magnesium sulfate (270 mg/kg) every 4 hours for 24 hours and 6 received saline solution. Six rats received intraperitoneal magnesium sulfate (270 mg/kg) every 12 hours for 2 weeks and 6 received saline solution. Rats were subsequently perfused and killed and their brains dissected and frozen. Cryostate sections were taken, labeled in vitro by one of three ligands for autoradiography assay, and mounted on tritium-sensitive film for 4 weeks. The ligands were tritiated glutamate agonist, N-methyl-D-aspartate binding site; tritiated glycine agonist, glycine binding site; and tritiated MK-801 noncompetitive antagonist, channel site. Optical density measurements of binding of 11 brain regions on each section were performed with an image analyzing system. RESULTS: N-methyl-D-aspartate receptor binding in the hippocampus was higher than in all other brain regions in all three experiments. Systemic administration of magnesium sulfate for 24 hours resulted in reduced tritiated glutamate binding, whereas long-term administration (2 weeks) resulted in significantly decreased tritiated glycine binding in all brain regions sampled. Binding of tritiated MK-801 was significantly increased in both short- and intermediate-term administration of magnesium sulfate. CONCLUSIONS: These data suggest that short-term magnesium sulfate administration results in increased inhibition of the ion channel. This effect is also continued with prolonged treatment, along with decreased sensitivity of the N-methyl-D-aspartate receptor channel complex to its agonists glutamate and glycine. This proposed time-dependent, twofold effect may provide insight into the mechanisms of magnesium sulfate's central anticonvulsant effect.