Effect of chronic administration of magnesium sulfate on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice.

This investigation was aimed to study the effect of magnesium on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice. Four groups of mice were given magnesium sulfate (MgSO4.7H2O) in drinking water at four different concentrations of 0.0 g/l (control), 2.5 g/l (low), 5.0 g/l (medium) and 10.0 g/l (high) respectively for a period of 16 weeks; these animals also received MPTP (30 mg/kg, intraperitoneally daily) during the last five days of Mg treatment. Other four groups of mice were given similar dose regimen of MgSO4 but received injections of saline instead of MPTP. Seventy-two hr after the last dose of MPTP, neurobehavioural studies including locomotor activity, pole climbing test and heart nociception test were performed and striata were collected for the analysis of dopamine. The results of this study show that treatment of mice with MgSO4 or MPTP individually has no effect on their behaviour. Concomitant administration of low dose of MgSO4 (2.5 g/l) along with MPTP produced increase in motor activity and latency to heat stimuli; whereas medium and high doses of MgSO4 in combination with MPTP produced opposite (as compared to low dose) effects resulting in a decrease in motor activity and latency to heat stimuli and increase in pole climbing time. However, MgSO4 dose-dependently exacerbated MPTP-induced depletion of striatal dopamine. The mortality was drastically increased (30-55%) in the animals receiving combined treatments of MPTP and MgSO4 as compared to the mice treated with MPTP alone (12%). This study clearly points towards the ability of MgSO4 to modify MPTP-induced neurotoxicity.