5-HT_1A receptor and apoptosis contribute to interferon-伪-induced 鈥渄epressive-like鈥?behavior in mice

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• 作者：Fengfeng Ping^a ; ^b ; ¹ ; Jing Shang^a ; ^b ; ¹ ; ^{shangjing2006@yahoo.com.cn} ; ^{yyylxh@126.com} ; Jia Zhou^a ; ^b ; Hongmei Zhang^a ; ^b ; Luyong Zhang^a ; ^b ; ^{drugscreen@126.com}
• 关键词：IFN-伪 ; &ldquo ; Depressive-like&rdquo ; behavior ; 5-HT1A receptor ; C57BL/6J mice ; Apoptosis
• 刊名：Neuroscience Letters
• 出版年：2012
• 期刊代码：52_03043940
• 类别：neu
• 出版时间：18 April, 2012
• 卷：514
• 期：2
• 页码：173-178
• 文件大小：881 K

摘要

Interferon-伪 (IFN-伪)-induced 鈥渄epressive-like鈥?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-伪 on the modulation of 5-HT_1A receptor and cellular apoptosis and their relationship. Our results showed that repeated administration of IFN-伪 (6 MIU/kg, s.c.) induced 鈥渄epressive-like鈥?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-伪 administration), but not by the standard antidepressant imipramine (10 mg/kg, i.p., 30 min before IFN-伪 administration) although both of them could ameliorate the depressive-like behavior of mice. These findings indicated that repeated injection with IFN-伪 provoked 鈥渄epressive-like鈥?behavior through cellular apoptosis, which could be ameliorated by the activation of 5-HT_1A receptor.