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

Background: 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.

Materials and Methods: Male Swiss mice (25–30 g) were used. Depression was induced by IFN-α 1600000 IU/kg, sc for six days, or CSA20 mg/kg, ip for 3 days as VA 25 mg/kg, and pretreatment was ip injected. After evaluating the locomotor activity, depression was assessed by forced swimming test (FST) and sucrose preference (SP) test. 

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

Conclusion: 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.