Antidepressant reversal of interferon-alpha-induced anhedonia

Interferon-alpha(IFN-alpha) is used clinically in the treatment of several pathologies such as hepatitis C and various cancers. The positive therapeutic potential is however often limited by negative secondary effects which include major depression, one of the cardinal symptoms of which is anhedonia which has been operationalized as a decreased sensitivity to rewards (inability to experience pleasure). Previous studies have demonstrated the existence of anhedonia in rats following an acute injection of IFN-alpha at doses corresponding to those used in clinical applications. If this previously demonstrated anhedonia is indeed part of a depression syndrome in rats, this behavioural symptom should be reversible by the administration of antidepressants. The objective of the present experiment was to determine whether two commonly used antidepressants (desipramine and fluoxetine) were effective in ameliorating IFN-alpha-induced anhedonia in rats. The experiment consisted of two phases. In the first, the effects of daily systemic injections of 104 units/kg of IFN-alpha (or vehicle) were evaluated with the three-bottle (1%, 8%, and 32%) sucrose-consumption test. In the second phase of the experiment, in addition to continued injections of IFN-, different groups received daily injections of desipramine (7.5 mg/kg ip), fluoxetine (7.5 mg/kg ip), or vehicle. The IFN-alpha injections during Phase 1 resulted in clear anhedonia, as expressed by increased consumption of the 32% solution and decreased consumption of 1% over the 33 days of this phase. After 15 days of antidepressant treatments, 32% sucrose consumption returned to baseline values. We have therefore confirmed that IFN-alpha-induced anhedonia is susceptible to reversal following chronic antidepressant treatment and thus it may appear timely to consider the prophylactic use of such in particular patients prescribed IFN in the clinic.