Decreased expression of serotonin 1A receptor in the dentate gyrus in association with chronic mild stress: A rat model of post-stroke depression

Wang, Shao-hua; Zhang, Zhi-jun; Guo, Yi-jing; Teng, Gao-jun; Chen, Bao-an

doi:10.1016/j.psychres.2008.07.006

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Volume 170, Issue 2 , Pages 245-251, 30 December 2009

Decreased expression of serotonin 1A receptor in the dentate gyrus in association with chronic mild stress: A rat model of post-stroke depression

Shao-hua Wang
- Department of Neurology and Institution of Cerebral Vascular Disease, ZhongDa Hospital, Southeast University, Nanjing, China
- Tel.: +86 25 83285148; fax: +86 25 83285132.
Zhi-jun Zhang
- Department of Neurology and Institution of Cerebral Vascular Disease, ZhongDa Hospital, Southeast University, Nanjing, China
- Corresponding author. Tel.: +86 25 83272023; fax: +86 25 83285132.
Yi-jing Guo
- Department of Neurology and Institution of Cerebral Vascular Disease, ZhongDa Hospital, Southeast University, Nanjing, China
Gao-jun Teng
- Institution of Molecular Imaging, Southeast University, Nanjing, China
Bao-an Chen
- Department of Neurology and Institution of Cerebral Vascular Disease, ZhongDa Hospital, Southeast University, Nanjing, China

Received 23 July 2007; received in revised form 11 February 2008; accepted 20 July 2008.

Abstract

Alterations of serotonin (5-HT) neurotransmission are implicated in post-stroke depression (PSD). Serotonin 1A (5-HT_1A) receptor-based abnormalities have been the focus of intensive study in depression. Here we investigated the expression of the 5-HT_1A receptor and gene in the hippocampal dentate gyrus (DG) by chronic mild stress (CMS) after stroke and the effect of citalopram. Male Sprague–Dawley rats were separated into control, stress only, ischemic stroke, PSD and citalopram-treated groups. The putative PSD animal model involved cerebral ischemia induced by left middle cerebral artery occlusion (MCAO) followed by exposure to CMS combined with single housing. All animals were assessed for depression-like behavior. The 5-HT_1A receptor and mRNA level in DG were quantified by Western immunoblotting and Real-time RT-PCR, respectively, on the 19th and 28th days after initiating CMS. PSD animals displaying a behavioral index of depression (anhedonia) have significantly decreased protein expression of 5-HT_1A receptors and mRNA level relative to ischemic stroke animals at each timepoint, respectively, and all these were reversed by citalopram. The dysfunction of the of 5-HT_1A receptor in DG may play an important role in the pathogenesis of PSD and become a potential target for therapeutic intervention in the rat. The results provide partial support for the psychosocial and biological etiology of PSD and further predict the etiologic validity of the PSD model.

Keywords: Post-stroke depression, 5-HT_1A receptor, Dentate gyrus, Hippocampus, Chronic mild stress, Citalopram