ABSTRACT
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 syn-thases(NOS)and various types of NOS were examined by molecular biology methods.The mice pretreated with NMDA re-ceptor antagonist MK-801(MK),NMDA,NO precursor L-arginine(L-ARG),endothelial NOS(eNOS)inhibitor Nω-ni-tro-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 antidepres-sant 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.