Effects of dimethyl fumarate in murine models of depression and anxiety

Abstract

Depression and anxiety are psychiatric disorders, which are leading causes of disability and often accompany chronic diseases. Increased oxidative stress occurs in both disorders. This study investigated the effects of dimethyl fumarate (DMF) in animal models of depression and anxiety. Different groups of mice were treated with either the vehicle, 50, 100 mg/kg DMF or imipramine and subjected to either the forced swim tes t (FST) or the tail suspension test (TST). Another set of mice were treated daily with either the vehicle, DMF 50 and 100 mg/kg and imipramine for two weeks and subjected to either the FST or TST. Thereafter, animals were sacrificed; whole brains isolated and brain catalase levels assayed. The same procedure was followed for evaluation of anxiolytic property of DMF using the staircase and hole-board tests as test indices and diazepam as the reference drug. In the test for depression, 50 and 100 mg/kg DMF significantly (p<0.05) reduced periods of immobility in both the FST and TST after acute and chronic drug administration; and significantly (p<0.05) increased brain catalase levels. In the test for anxiolysis, both doses of DMF did not produce significant changes in the staircase test indices following acute and chronic drug treatment. However, low dose DMF -50 mg/kg significantly increased (p<0.05) the number of head dips in the holeboard test post chronic drug treatment; both doses increased levels of cata lase in the brain. DMF exhibited antidepressant activity and anxiolytic properties and increased levels of catalase in the brains of mice .

Keywords: Catalase; Forced swim test; Staircase test; Antioxidants; Depression