Resveratrol exerts anxiolytic-like effects through anti-inflammatory and antioxidant activities in rats exposed to chronic social isolation.

Emerging evidence has confirmed resveratrol's (RES) antioxidant, anti-inflammatory, and antidepressant effects. The beneficial effects of RES were confirmed for several emotional and cognitive deficits. This research aimed to assess the impacts of RES on behavior and hippocampal levels of anti-inflammatory and pro-inflammatory factors in rats exposed to chronic social isolation (SI) stress, which is known to induce mental disorders such as depressive-like behavior. The animals were treated by RES (20, 40, or 80 mg/kg/intraperitoneally) for 28 days following a 28-day exposure to stress. Behavioral tests, including the forced swim test (FST), open-field test (OFT), tail suspension test (TST), and sucrose preference test (SPT), assessed depressive symptoms. Finally, the animals were sacrificed, and molecular studies (qPCR and ELISA) were performed. Exposure of animals to SI dramatically increased the immobility of animals in TST and FST, enhanced the time spent in the open-field peripheral zone of the OFT, and reduced the sucrose preference rate. In addition, SI increased serum levels of corticosterone and hippocampal content of MDA, whereas it reduced hippocampal SOD and CAT activities. Moreover, SI upregulated the expression of IL-10, IL-18, and IL-1β and downregulated the expression of TGF-β in the hippocampus. RES treatment (40 & 80 mg/kg) significantly improved the behavioral alterations through the modulation of neuroinflammation and oxidative stress. The 20 mg/kg RES dose was inefficient for treating SI-induced depressive-like behavior. These results indicated that RES attenuated depressive-like behavior in prolonged stressed animals. These properties might be associated with RES-mediated improvements in serum corticosterone and hippocampal inflammatory and oxidative stress biomarkers.