Resveratrol ameliorates physical and psychological stress-induced depressive-like behavior

Abstract Objectives Depression is a mental disorder that profoundly affects all aspects of life, but currently, antidepressants have some problems with their effectiveness and side effects. Resveratrol is a compound that has the ability to regulate the hypothalamic-pituitary-adrenal axis. This study aimed to determine resveratrol’s effect on physical and psychological stress-induced depressive-like behavior. Methods Mice were divided into control, physical stress, psychological stress groups. Treatment was conducted with fluvoxamine 20 mg/kg and resveratrol 20, 40, and 80 mg/kg for seven days. The depressive-like state was evaluated using a forced swim test (FST), tail suspension test (TST), and open field test (OFT). Results Physical stress and psychological stress induction increase the immobility time on FST and TST. Besides, there is an increase in time in central on OFT, which indicates an anxiety or mental illness-like behavior. However, the OFT examination on sniffing, rearing, grooming, and crossing behavior did not show a significant difference. Resveratrol 80 mg/kg and fluvoxamine 20 mg/kg were significantly reduced immobility time at TST compared to the physical stress group. While in psychological stress, resveratrol 80 mg/kg tended to decrease immobility time but not significant. A significant increase in time in central duration was seen in the resveratrol 40 mg/kg compared to the psychological stress. Stress induction causes increased amygdala corticotrophin-releasing factor (CRF) mRNA expression. However, neither resveratrol nor fluvoxamine affected amygdala CRF mRNA expression. Conclusions Resveratrol ameliorates depressive-like behavior induced by physical and psychological stress.