L-arginine as a potential antidepressant: Effects on cognitive function and antioxidant enzyme activity in depressed rats

Abstract

The potential antidepressant effects of dietary L-arginine (L-Arg) were investigated in male white laboratory rats with corticosterone-induced depression. Daily administration of L-Arg at a dose of 150 mg/kg for 14 consecutive days significantly alleviated depressive-like behaviors and improved cognitive performance. Furthermore, L-Arg supplementation restored serotonin levels in the prefrontal cortex and hippocampus, which had been reduced following intraperitoneal corticosterone injection. To evaluate the antioxidant properties of L-Arg, quantitative changes in malondialdehyde (MDA) and nitric oxide (NO) levels were measured in the prefrontal cortex and hippocampal cells of depressive rats following L-Arg administration. The findings revealed that L-Arg normalized lipid peroxidation processes that had been enhanced under depressive conditions. L-Arg treatment significantly reduced elevated levels of these oxidative stress markers. Additionally, it increased the activity of key antioxidant enzymes, including mitochondrial superoxide dismutase (SOD) and catalase, whose activities had been suppressed in the depressive state. Kinetic analysis of enzymatic reactions indicated that the increased activity of these antioxidant enzymes in the brain cells of depressive rats was not due to structural modifications of the enzymes, but rather to an increase in their abundance. This effect is likely attributable to the activation of biosynthetic processes in brain cells triggered by L-Arg administration.