Resveratrol exerts antidepressant properties in the chronic unpredictable mild stress model through the regulation of oxidative stress and mTOR pathway in the rat hippocampus and prefrontal cortex

• Published in: Behavioural brain research Vol. 302; pp. 191 - 199
• Main Authors: liu, Song, Li, Tong, Liu, Hansen, Wang, Xueer, bo, Shishi, Xie, Yunkai, Bai, Xuemei, Wu, Lin, Wang, Zhen, Liu, Dexiang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-04-2016
• Subjects: Akt; Animals; Antidepressive Agents - pharmacology; Antidepressive Agents - therapeutic use; Brain - drug effects; Brain - metabolism; Chronic Disease; Chronic unpredictable mild stress (CUMS); Depression; Depression - drug therapy; Depression - etiology; Depression - pathology; Disease Models, Animal; Exploratory Behavior - drug effects; Food Preferences - drug effects; Lipid Peroxidation - drug effects; Locomotion - drug effects; Male; mTOR; Oxidative Stress - drug effects; Polygonum cuspidatum; Rats; Rats, Wistar; Resveratrol; Signal Transduction - drug effects; Stilbenes - pharmacology; Stilbenes - therapeutic use; Stress, Psychological - complications; Swimming - psychology; Time Factors; TOR Serine-Threonine Kinases - metabolism; BDNF; FST; CUMS; SOD; Depression; MDA; Akt; PFC; ROS; Resveratrol; mTOR; Chronic unpredictable mild stress (CUMS); GSH
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2016.01.037

•Resveratrol reversed the CUMS-induced behavioral abnormalities in rats.•Resveratrol exhibited its antioxidant action.•Resveratrol reversed CUMS-induced Akt/mTOR phosphorylation.
Depression is one of the most common neuropsychiatric disorders and has been associated with oxidative stress and brain protein alterations. Resveratrol is a natural polyphenol enriched in Polygonum cuspidatum and has diverse biological activities including potent antidepressant-like effects. The present study attempts to explore the mechanisms underlying the antidepressant-like action of resveratrol by measuring oxidative stress parameters and phosphorylation of AKT/mTOR pathway in the rat hippocampus and prefrontal cortex (PFC) exposed to the chronic unpredictable mild stress (CUMS). Male Wistar rats were subjected to CUMS protocol for a period of 4 weeks to induce depressive-like behavior. The results showed that resveratrol treatment (80mg/kg/i.p. 4 weeks) significantly reversed the CUMS-induced behavioral abnormalities (reduced sucrose preference, increased immobility time and decreased locomotor activity) and biochemical changes (increased lipid peroxidation and decreased superoxide dismutase). Additionally, CUMS exposure significantly decreased phosphorylation of Akt and mTOR in the hippocampus and PFC, while resveratrol treatment normalized these parameters. In conclusion, our study showed that resveratrol exerted antidepressant-like effects in CUMS rats, which was mediated in part by its antioxidant action, up-regulation of phosphor–Akt and mTOR levels in the hippocampus and PFC.