The Widely-used Anti-viral Drug Interferon-alpha Induces Depressive- and Anxiogenic-like Effects in Healthy Rats

Interferon-alpha (IFN-alpha) is a naturally occurring human cytokine that is a key therapy in the treatment of several viral diseases and cancers. However, treatment can produce significant neuropsychiatric and neurotoxic adverse events, including depression and anxiety. Here we investigated the effects of a clinically-comparable treatment regime of IFN-alpha on depressive- and anxiety-like behaviour in rats; and also examined frontal-cortical and hippocampal BDNF levels. Rats treated with IFN-alpha for four weeks showed significant increases in depressive- and anxiety-like behaviour. Further experimental investigation revealed that hedonic dysregulation (stronger preference for a sweet solution) did not emerge until the second week of treatment, and became more persistent as treatment progressed. No significant IFN-alpha-induced changes in BDNF levels were found. These results indicate that the affective deficits seen in patients may be modelled in healthy animals. This model may represent a novel tool to investigate the extent of and mechanisms underlying the IFN-alpha psychiatric syndrome.