Melatonin prevented depressive-like behavior following cyclosporine A or interferon-α administration in mice

Abstract

Background: Cyclosporine A (CYA) prevents graft rejection after transplantation, interferon-α (IFN-α ) is a natural cytokine prescribed in some types of malignancies and hepatitis C virus. However neurologic complication such as depression is a side effect of chronic use of these drugs. Melatonin apart from its effect on regulating the circadian rhythm, has a potent antioxidant effect and inhibits N-methyl-d-aspartic acid (NMDA) current. The goal was to evaluate the antidepressant effect of melatonin following IFN-α, and CYA administration in mice. Methods: Male NMRI mice (25-30 g) were used, IFN-α (1600000 IU/kg, sc), CYA (20 mg/kg, ip), melatonin (50 mg/kg, ip), and fluoxetine (20 mg/kg, ip) were administered daily. After evaluating the locomotor activity, depression was assessed by splash test, forced swimming test (FST), and the sucrose preference test. Results: While there was no significant difference in locomotor activity amongest different anamal groups, following melatonin pretreatment with IFN-α immobility time in FST significantly reduced (58.50±19.4s, p