The antidepressant effects of l-arginine on chronic mild stress-induced depression by augmenting the expression of brain-derived neurotrophic factor in rats.

In the present study, the antidepressant effects of l-arginine in a rat model of chronic mild stress-induced depression were investigated. Animals were divided into group I (sham), group II (control, depression), group III (10 mg/kg l-arginine), group IV (20 mg/kg l-arginine), and group V (10 mg/kg venlafaxine, positive control). The doses were orally administered for 30 consecutive days. Sucrose preference analysis as well as forced swim and open field tests were performed. Serum cortisol, nitric oxide (NO), and monoamine levels in brain tissue were then measured. Brain-derived neurotrophic factor (BDNF) expression was also examined. Supplementation with l-arginine significantly increased the sucrose preference ratio, locomotor activity, and monoamines and decreased serum cortisol and NO levels. The mRNA and protein expression of BDNF in the brain tissue was significantly reduced (>50 %) in control rats. However, supplementation with l-arginine significantly increased BDNF mRNA expression (>50 %) in both groups. Similarly, increased BDNF protein expression after l-arginine treatment was confirmed using Western blot and immunohistochemical analyses. In conclusion, l-arginine supplementation may be effective against chronic stress-induced depression.