Neuropsychopharmacological effect of sesamol in unpredictable chronic mild stress model of depression: behavioral and biochemical evidences

A complex relationship exists among stressful situations, body's reaction to stress, and the onset of clinical depression. Chronic unpredictable stressors can produce a situation similar to clinical depression, and such animal models can be used for the preclinical evaluation of antidepressants. Many findings have shown that the levels of proinflammatory cytokines (e.g., TNF-alpha) and oxidative stress (increased lipid peroxidation, decreased glutathione levels, and endogenous antioxidant enzyme activities) are increased in patients with depression. Sesamol, a phenolic derivative with a methylenedioxy group, is a potent inhibitor of cytokine production as well as an antioxidant. The present study was designed to investigate the effect of sesamol on unpredictable chronic stress-induced behavioral and biochemical alterations in mice. Animals were subjected to different stress paradigms daily for a period of 21 days to induce depressive-like behavior. The sucrose preference, immobility period, locomotor activity, memory acquisition, and retention were evaluated. Chronic treatment with sesamol significantly reversed the unpredictable chronic stress-induced behavioral (increased immobility period, reduced sucrose preference), biochemical (increased lipid peroxidation and nitrite levels; decreased glutathione levels, superoxide dismutase and catalase activities), and inflammation surge (serum TNF-alpha) in stressed mice. The study revealed that sesamol exerted antidepressant-like effects in behavioral despair paradigm in chronically stressed mice, specifically by modulating central oxidative-nitrosative stress and inflammation.