D-serine, a selective glycine/N-methyl-D-aspartate receptor agonist, antagonizes the antidepressant-like effects of magnesium and zinc in mice.

Zinc and magnesium are potent inhibitors of the N-methyl-D-aspartate (NMDA) receptor complex. Recent data demonstrate that both zinc and magnesium, like other NMDA receptor antagonists, exhibit antidepressant-like activity in rodent screening tests and depression models. In the present study, we investigated the effect of D-serine (agonist for the glycine(B) site of the NMDA receptor complex; 100 nmol/mouse, icv) on magnesium (30 mg/kg, ip)- and zinc (5 mg/kg, ip)-induced activity during a forced swim test (FST) in mice. The antidepressant-like effect observed during FST for both ions was abolished by D-serine co-treatment. The present study indicates that the NMDA receptor complex, especially the glycine(B) site, plays a role in the antidepressant-like activity of magnesium and zinc in the FST in mice.