The antidepressant- and anxiolytic-like effects of magnesium, an N-methyl-D-aspartate (NMDA) glutamate receptor inhibitor, were studied in mice using the forced swim test and elevated plus-maze test, respectively. The doses of 20 and 30 mg Mg/kg, reduced immobility time in the forced swim test exerting antidepressant-like activity. In the elevated plus-maze test, magnesium at the same doses produced anxiolytic-like effect. The doses of magnesium active in both tests did not affect locomotor activity. To evaluate the tolerance to these effects, we also performed experiments on the following acute/chronic magnesium treatment schedule: chronic saline and saline challenge at 0.5 h before behavioral experiments or serum magnesium determination (S+S), chronic saline and magnesium challenge (S+Mg), chronic magnesium and saline challenge (Mg+S), chronic magnesium and magnesium challenge (Mg+Mg). The antidepressant- and anxiolytic-like effect of magnesium was demonstrated in groups treated acutely and chronically with magnesium (Mg+Mg), but not in the Mg+S group. Moreover, these effects seem to be connected with at least 58% increase in serum magnesium concentration. The results indicate that magnesium induces the antidepressant- and anxiolytic-like effects without tolerance to these activities, which suggests a potential antidepressant and anxiolytic activity of magnesium in these disorders in humans. © 2004 Elsevier Inc. All rights reserved.
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