Pharmacological Screening of Gentisic acid for Antidepressant Activity in Unstressed and Stressed Mice

Background: Gentisic acid has been reported to show neuroprotective effect. But its effect on depression is not available in the literature. So we evaluated the effect of this compound on depressive behavior in unstressed (normal) mice and stressed mice. Materials and Methods: Swiss albino male mice were given unpredictable mild stressors for twenty-one consecutive days to produce depressive behavior. Gentisic acid (25, 50, 100 mg/kg) and fluoxetine (20 mg/kg) were administered orally for twenty-one consecutive days. Depressive behavior was detected by tail suspension test and sucrose preference test. After behavioral testing, biochemical estimations were performed in plasma and brain. Histopathological studies on brain were also performed. Results: Immobility time of mice in tail suspension test was remarkably decreased by gentisic acid (50 and 100 mg/kg). Gentisic acid also restored decreased sucrose preference in mice subjected to stress paradigm. It remarkably lowered concentration of plasma nitrite, brain monoamine oxidase- A, malondialdehyde, TNF-α; and increased concentration of catalase and GSH in normal mice and also stressed mice. It also remarkably lowered plasma corticosterone concentration in stressed mice. Histopathological studies indicated protection by gentisic acid against hyperchromatic nuclei in brain. Conclusion: Gentisic acid produced remarkable antidepressant effect in normal mice and also stressed mice. The possible mechanisms for the observed antidepressant effect of gentisic acid might be through inhibition of brain MAO-A, amelioration of neuroinflammation and oxidative stress; and protection against hyperchromatic nuclei in brain. Moreover, antidepressant effect of gentisic acid in stressed mice might be through lowering of plasma corticosterone concentration.