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.
Fahey
Bríana
B
Trinity College Institute of Neuroscience, Lloyd Building, Trinity College Dublin, Dublin 2, Ireland.
Hickey
Barry
B
Kelleher
Dermot
D
O'Dwyer
Anne-Marie
AM
O'Mara
Shane M
SM
D000818:Animals; D001007:Anxiety / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D016009:Chi-Square Distribution; D003216:Conditioning, Operant / Q000187:drug effects; D003863:Depression / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D005518:Food Preferences / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D016898:Interferon-alpha; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012439:Saccharin / Q000008:administration & dosage; D013550:Swimming
D019208:Brain-Derived Neurotrophic Factor; D016898:Interferon-alpha; D012439:Saccharin