Vanillic Acid Prevents Interferon-alpha and Cyclosporine A-induced Depressant-like Behavior in Mice

Interferon-alpha (IFN-α) is a useful therapy for some types of cancers and viral infections. Cyclosporine A (CSA) is an immunosuppressant drug used to reduce the risk of graft rejection. Chronic use of IFN-α and CSA are related to psychological symptoms such as depression. Vanillic acid (VA) is a naturally occurring flavoring substance with antidepressant potential. The aim of this study was to evaluate the effect of VA on depression caused by these two drugs in a mice model.

Male Swiss mice (25–30g) were used. Depression was induced by IFN-α 1600000 IU/kg, sc for six days, or CSA20mg/kg, ip for 3 days as VA 25mg/kg, and pretreatment was ip injected. After evaluating the locomotor activity, depression was assessed by forced swimming test (FST) and sucrose preference (SP) test.

The selected treatments did not cause significant changes in the locomotor activity. IFN-α significantly increased the immobility time during FST (184.5±12.9s vs. vehicle 107.1±11.4s) indicating depressive-like effect, and VA pretreatment reversed it (94.8±17.8s vs. IFN-α), SP increased to 76%. CSA also increased the immobility time during FST (160.3±3.4 s vs. vehicle 113.2±7.6 s; P < 0.05), VA pretreatment reduced it (81.8±16.9s, vs. cyclosporine; P < 0.001), and SP increased from 38% to 75%. SP results were in agreement with FST results.

VA showed useful effect against IFN-α and cyclosporine-induced depression in mice. Further clinical studies regarding VA antidepressant effect in patients receiving IFN-α or CSA are warranted.