Rutin co-treatment prevented cognitive impairment/depression-like behavior and decreased IDO activation following 35 days of ethanol administration in male Wistar rats.

Alcohol (ethanol) is among the most popularly consumed beverages globally. Ethanol was earlier demonstrated to elicit cognitive impairment and depressive-like effects in both human and animal studies. Rutin (R) is known for its antioxidant, anti-inflammatory, immunomodulatory, and anti-depressive properties, among others. Herein, we investigate the impact of rutin on ethanol-induced cognitive impairment and depressive-like effects in rats and the involvement of the indoleaminergic pathway. Three groups of eight rats each were orally exposed to drinking water (group 1), ethanol (5 g/kg body weight)-group 2 (via oral gavage), and ethanol + R (5 g/kg body weight + 50 mg/kg body weight)-group 3 (via oral gavage) for 35 days. Results showed that exposure to ethanol significantly (p < 0.0001) reduced spontaneous alternation in the Y-maze and increased immobility time in the tail suspension test (TST), which indicates cognitive impairment and depressive-like behavior in rats. We observed increased IDO activity/expression, and inflammatory responses, with attendant disruption in antioxidant systems and concomitant elevation in malondialdehyde (MDA) levels in the cerebral cortex and hippocampus. Following rutin co-exposure, an ethanol-mediated increase in indoleamine 2,3-dioxygenase [IDO] activity/expression and decrease in antioxidant enzymes, in addition to an increase in markers of inflammatory response and MDA production, was significantly (p < 0.0001) prevented compared with controls. Additionally, altered behavioral indices were prevented by rutin co-exposure. Taken together, these findings reveal the involvement of the indoleaminergic pathway in rutin preventive influence against ethanol-induced cognitive impairment and depressive-like behavior in rats.