Lycopene Ameliorates Brain Oxidative Stress and Exhibits Antidepressant, Antianxiety, and Motor Coordination-Enhancing Effects in Rats via Increased Serotonergic Transmission

Depression and anxiety impair motor coordination, leading to functional disability. While current therapies are effective, they do not target increased brain oxidative stress, a key underlying cause. Natural antioxidants like lycopene (LYC), alone or with fluoxetine (FLX), may offer a therapeutic strategy. This study evaluated LYC’s effects on depression, anxiety, and motor coordination dysfunction. Thirty-six rats were divided into six groups (6 per group). Treatment groups received LYC orally once daily at 5, 10, or 20 mg/kg, or a combination of FLX (20 mg/kg) and LYC (20 mg/kg). The standard group received FLX (20 mg/kg), while the control group received a vehicle, for 10 days. Behavioural studies, including the forced swim, hole board, elevated plus maze, and rotarod tests, were conducted on the 10th day of the study. Additionally, biochemical analyses measured brain levels of glutathione (GSH), thiobarbituric acid reactive substances (TBARS), and serotonin. Behavioural assessments revealed that the rats treated with LYC (20 mg/kg), alone and in combination with FLX (20 mg/kg), showed significant (P<0.05) antidepressant and antianxiety activity, along with improved motor coordination, moreover, there was a significant (P<0.05) increase in brain levels of GSH and serotonin along with decrease in TBARS compared to control rats displaying depressive and anxious behaviour. Furthermore, the combination treatment did not significantly surpass the effects of individual treatments in most parameters, indicating an additive rather than a synergistic effect. Hence, LYC reduced brain oxidative stress, enhanced serotonin levels, and alleviated depression, anxiety, and motor dysfunction in rats, possibly via the serotonergic pathway.