Antidepressant- and anxiolytic-like activity of magnesium in mice

Pharmacol Biochem Behav. 2004 May;78(1):7-12. doi: 10.1016/j.pbb.2004.01.006.


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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology
  • Anti-Anxiety Agents / therapeutic use*
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use*
  • Anxiety / drug therapy*
  • Anxiety / psychology
  • Magnesium / pharmacology
  • Magnesium / therapeutic use*
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Mice


  • Anti-Anxiety Agents
  • Antidepressive Agents
  • Magnesium