5-HT1A receptor and apoptosis contribute to interferon-α-induced “depressive-like” behavior in mice

Interferon-α (IFN-α)-induced “depressive-like” behavior is a major limitation for the treatment of hepatitis C virus (HCV), especially for patients with psychiatric disorders. Recently, serotonin 1A (5-HT1A) receptor and cellular apoptosis are involved in mechanism(s) contributing to depression. To gain insight into this mechanism(s), we used C57BL/6J mice to examine the impact of IFN-α on the modulation of 5-HT1A receptor and cellular apoptosis and their relationship. Our results showed that repeated administration of IFN-α (6 MIU/kg, s.c.) induced “depressive-like” behavior of mice in the forced swim test, tail suspension test and sucrose preference test. Besides, the depressive mice exhibited a notable downregulation of 5-HT1A receptor and upregulation of cleaved caspase-3 and Bax/Bcl-2 ratio. These changes could be blocked by the 5-HT1A receptor agonist 8-OH-DPAT (0.5 mg/kg, i.p., 30 min before IFN-α administration), but not by the standard antidepressant imipramine (10 mg/kg, i.p., 30 min before IFN-α administration) although both of them could ameliorate the depressive-like behavior of mice. These findings indicated that repeated injection with IFN-α provoked “depressive-like” behavior through cellular apoptosis, which could be ameliorated by the activation of 5-HT1A receptor.

► Repeated administration of IFN-α subcutaneously induced depression in C57BL/6J mice.
► 5-HT1A receptor is involved in IFN-α-induced depression.
► Apoptosis is involved in IFN-α-induced depression.
► Upregulation of 5-HT1A receptor alleviates apoptosis and thus ameliorates depression.