Curcumin produces antidepressant effects via activating MAPK/ERK-dependent brain-derived neurotrophic factor...

The potential antidepressant effects of curcumin have been demonstrated in various animal models of depression, however, there is little information regarding the site and mechanisms of curcumin in promoting antidepressant effects. The present study attempts to explore the mechanisms underlying the antidepressant-like action of curcumin by measuring the contents of brain derived neurotrophic factor (BDNF) in the amygdala of animal model of depression. The results showed that treatment with curcumin (40 mg/kg, i.p.) significantly reduced depressive-like behaviors of mice in the forced swim test. Chronic administration of curcumin (40 mg/kg, i.p., 21 days) increased BDNF protein levels in the amygdala and this enhancement was suppressed by pretreatment with the extracellular signal-regulated kinase (ERK) inhibitor SL327. Additionally, the increased levels of ERK phosphoryation in the amygdala by curcumin were blocked by the ERK inhibitor, and inhibition of this kinase prevented the antidepressant effects of curcumin. All of these effects of curcumin, were essentially identical to that observed with the clinical antidepressant, fluoxetine. These results suggest that the antidepressant-like effects of curcumin in the forced swim test are mediated, at least in part, by an ERK-regulated increase of BDNF expression in the amygdala of mice.