Involvement of mGlu5 and NMDA receptors in the antidepressant-like effect of acamprosate in the tail suspension test

Accumulating evidence supports the hypothesis that modulation of glutamatergic system via NMDA receptors and mGlu5 receptors might be an effective antidepressant therapy. However, clinical application of NMDA and mGlu5 antagonists in the therapy of depression is still an open question. In the present study we investigated potential antidepressant-like effect of a functional NMDA and mGlu5 receptor antagonist, acamprosate, which has been used in the therapy of human alcoholics as an anti-craving drug for more than 20 years and is considered as a safe substance. We have found potential antidepressant-like effect of acamprosate at doses of 100-400 mg/kg in the TST in C57BL/6J mice. Furthermore we have shown that the antidepressant-like effect of acamprosate used at a dose of 200 mg/kg was dependent on NMDA and mGlu5 receptor blockade, since NMDA (25 mg/kg) and mGlu5 receptor positive allosteric modulator, CDPPB (3 mg/kg), antagonized its activity in the TST. These data suggest that acamprosate may induce antidepressant-like effect and that NMDA and mGlu5 receptors are crucial targets of acamprosate in this action.

► A potential antidepressant-like effect of acamprosate was investigated. ► Acamprosate induced dose-dependent antidepressant-like effect in the TST in mice. ► The effect of acamprosate depended on NMDA and/or mGlu5 receptor blockade.