Antidepressant effect of dextromethorphan and its mechanism

AIM:To investigate the antidepressant effect of dextromethorphan (DXM) and its mechanism. METHODS:The antidepressant effect of DXM was observed by the methods of forced swimming test, tail suspension test and open field test. The N-methyl-D-aspartate (NMDA) receptor activity in brain, and the effects of total nitric oxide synthases (NOS) and various types of NOS were examined by molecular biology methods. The mice pretreated with NMDA receptor antagonist MK-801 (MK), NMDA, NO precursor L-arginine (L-ARG), endothelial NOS (eNOS) inhibitor N^ω-nitro-L-arginine methyl ester (L-NAME), inducible NOS (iNOS) inhibitor aminoguanidine (AG), neuronal NOS (nNOS) inhibitor 7-nitroindole (7-NI) or phosphodiesterase 5 inhibitor sildenafil were given DXM to explore the mechanism of DXM as an antidepressant. RESULTS:DXM had a dose-dependent antidepressant effect. DXM inhibited the activity of brain NMDA receptor in a dose-dependent manner, and inhibited the expression of eNOS and nNOS. MK, L-NAME and 7-NI were able to promote the antidepressant effect of DXM. NMDA, L-ARG and sildenafil were able to inhibit the antidepressant effect of DXM. AG did not influence the antidepressant effect of DXM. CONCLUSION:DXM has an antidepressant effect, and NMDA receptor and L-ARG-NO-cGMP signaling pathways are involved in this process.