title: 5-HT(1A) receptor and apoptosis contribute to interferon-α-induced "depressive-like" behavior in mice.
abstract: 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-HT(1A)) 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-HT(1A) 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-HT(1A) receptor and upregulation of cleaved caspase-3 and Bax/Bcl-2 ratio. These changes could be blocked by the 5-HT(1A) 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-HT(1A) receptor.
authors.affiliation: Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Fengfeng
authors.initials: F
authors.lastname: Ping
authors.forename: Jing
authors.initials: J
authors.lastname: Shang
authors.forename: Jia
authors.initials: J
authors.lastname: Zhou
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zhang
authors.forename: Luyong
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D003863:Depression / Q000139:chemically induced / Q000378:metabolism*; D019417:Hindlimb Suspension; D007099:Imipramine / Q000494:pharmacology; D016898:Interferon-alpha / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D016898:Interferon-alpha; D044282:Receptor, Serotonin, 5-HT1A; D007099:Imipramine