Anxiolytic and Anti-Inflammatory Effects of Agomelatine in a LPS-Induced In vivo Model

Neuroinflammation, which results from alterations in the immune system, plays a central role in the pathophysiology of major depressive disorder by inducing neurotoxic effects in brain regions involved in emotion regulation. Agomelatine (AGO), a novel antidepressant, may influence emotional regulation by modulating the critical mechanisms of the interaction between autophagy and neuroinflammation. Lipopolysaccharide (LPS) is an endotoxin that causes depression-like behavior by increasing microglial activation and inflammatory response in the brain. To evaluate the anxiolytic and anti-inflammatory effects of agomelatine, a rat model of depression was induced with LPS. A total of 24 male rats were used in this study, divided into three experimental groups (n=8): control, LPS, and LPS+AGO. Rats in the LPS and LPS+AGO groups received AGO (40 mg/kg, intragastrically) and LPS (0.5 mg/kg, i.p.) for the first 10 days, respectively. AGO was administered daily to the LPS+AGO group for of the 21-day study period. Behavioral assessments were conducted using the open field test. At the conclusion of the experiment, IL-1β and IL-10 levels were measured in the hippocampus, prefrontal cortex, and serum samples using ELISA. According to these results, AGO was found to significantly increase IL-10 levels, particularly in the prefrontal cortex, while decreasing IL-1β levels in the hippocampus. These results confirmed that agomelatine has anxiolytic and anti-inflammatory effects.