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

Abstract

Cyclosporine A (CYA) is prescribed to prevent graft rejection after transplantation. Interferon-α (IFN-α), a natural cytokine, is prescribed for some types of malignancies, and hepatitis C virus. But both may cause neurologic complications such as depression following their chronic use. Melatonin is a hormone that helps regulate the circadian rhythm, additionally the melatonin system is connected to depression. The goal was evaluating the antidepressant effect of melatonin following IFN-α, and CYA administration in mice. 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. There was no significant difference in the locomotor activity amongest different animal groups. Follow- ing melatonin and IFN-α co-administration immobility time in FST decreased (58.50±19.4s, p<0.01); and during the splash test grooming time increased significantly (114.3±15.3s, p<0.01) compared to the IFN-α alone group, and sucrose preference rose up to 70%. After melatonin and CYA co-administration immobility time during FST decreased (42.33±9.9s, p<0.001); and grooming time increased significantly (103±10.5s, p<0.001) compared to the CYA alone group, sucrose preference also increased up to 93%. The changes induced by melatonin in these experiments were similar to changes made by fluoxetine. Melatonin prevented depression behavior (despair, apathy, and anhedonia) induced by IFN-α, or CYA in mice. The mechanism involved in melatonin antidepressant-like effect warrants further investigations.

Keywords

• depression
• cyclosporine A
• interferone-alfa
• melatonin
• animal model

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