Antidepressant-like effects of 1-methylnicotinamide in a chronic unpredictable mild stress model of depression

Depression is one of the most common psychiatric disorders, and there is strong demand for developing novel antidepressants with better efficacy and less adverse effects. 1-Methylnicotinamide (MNA) is a main metabolite of nicotinamide and has been demonstrated to possess biological effects in the brain. This study aimed to evaluate the antidepressant-like effects of MNA in mice, and the possible antidepressant mechanism was also determined. The forced swim test (FST), tail suspension test (TST), chronic unpredictable mild stress (CUMS) model of depression, western blotting method and K252a (a pharmacological inhibitor of the BDNF receptor) were used together in the present study. It was found that a single injection of MNA (100 and 200 mg/kg) displayed notable antidepressant-like potential in the FST and TST without affecting the locomotor activity of mice. Repeated administration of MNA (100 and 200 mg/kg) for 2 weeks fully reversed not only the CUMS-induced depressive-like symptoms in mice but also the CUMS-induced decrease in the hippocampal BDNF signaling pathway. Furthermore, the usage of K252a fully blocked the antidepressant-like effects of MNA in the FST, TST and CUMS model of depression. Collectively, MNA possess an antidepressant-like effect in mice which is mediated, at least in part, through promoting the hippocampal BDNF signaling pathway.