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Chronic blockade of glucocorticoid receptors by RU486 enhances lipopolysaccharide-induced depressive-like behaviour and cytokine production in rats
Wang, Donglin1,3; Lin, Wenjuan1,2; Pan, Yuqin1,3; Kuang, Xueying1; Qi, Xiaoli1; Sun, Han1,3; Lin, WJ (reprint author), Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, 4A Datun Rd, Beijing 100101, Peoples R China.
2011-05-01
Source PublicationBRAIN BEHAVIOR AND IMMUNITY
ISSN0889-1591
SubtypeArticle
Volume25Issue:4Pages:706-714
Contribution Rank1
Abstract

Although accumulating evidence supports a role for cytokines in the pathophysiology of depression, the cytokine hypothesis of depression is debatable. It has been suggested that neuroendocrine and immune systems acting in concert may have roles in the development and the maintenance of the disease. Glucocorticoid receptor (GR) is the key element which exerts both anti-inflammatory and cytokineinhibiting effects. Whether functional changes of GR are involved in the pathophysiology of cytokineinduced depression remains elusive. In the present study, the effects of both acute and chronic GR blockade on depressive-like behaviour and cytokine production induced by lipopolysaccharides (LPS), cytokine inducer, were investigated in rats. Acute or chronic blockade of GR was achieved by a single administration or repeated administrations, respectively, of the GR antagonist RU486 (RU). Behavioural measurements, including saccharin preference, locomotor activity, and immobility time, were assessed. The serum levels of proinflammatory cytokines (TNFa, IL-1b, and IFNc) were determined by ELISA. The results showed that LPS induced significant but transient depressive-like behaviour. Repeated, but not single, administration of RU significantly enhanced and prolonged LPS-induced depressive-like behavior and an increase in the serum production of TNFa and IFNc. These results indicate that the effective blockade of GR enhanced the depressive-like behaviour induced by cytokines. Findings from this study suggest that GR dysfunction may be an important contributing factor to the development of cytokine-related depression. These findings add to the growing evidence of mechanisms by which cytokines influence depression.

; Although accumulating evidence supports a role for cytokines in the pathophysiology of depression, the cytokine hypothesis of depression is debatable. It has been suggested that neuroendocrine and immune systems acting in concert may have roles in the development and the maintenance of the disease. Glucocorticoid receptor (GR) is the key element which exerts both anti-inflammatory and cytokine-inhibiting effects. Whether functional changes of GR are involved in the pathophysiology of cytokine-induced depression remains elusive. In the present study, the effects of both acute and chronic GR blockade on depressive-like behaviour and cytokine production induced by lipopolysaccharides (LPS), cytokine inducer, were investigated in rats. Acute or chronic blockade of GR was achieved by a single administration or repeated administrations, respectively, of the GR antagonist RU486 (RU). Behavioural measurements, including saccharin preference, locomotor activity, and immobility time, were assessed. The serum levels of proinflammatory cytokines (TNF alpha IL-1 beta, and IFN gamma) were determined by ELISA. The results showed that LPS induced significant but transient depressive-like behaviour. Repeated, but not single, administration of RU significantly enhanced and prolonged LPS-induced depressive-like behaviour and an increase in the serum production of TNF alpha and IFN gamma. These results indicate that the effective blockade of GR enhanced the depressive-like behaviour induced by cytokines. Findings from this study suggest that GR dysfunction may be an important contributing factor to the development of cytokine-related depression. These findings add to the growing evidence of mechanisms by which cytokines influence depression. (C) 2011 Elsevier Inc. All rights reserved.
KeywordRU486 Glucocorticoid receptor Lipopolysaccharides Cytokines Depressive-like behaviour
Subject AreaMedical Psychology
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Indexed BySCI
Language英语
Funding OrganizationNational Natural Science Foundation of China [30770718] ; Chinese Academy of Sciences [KSCX2-2-03, KSCX2-EW-J-8]
Project Intro.This research was supported by the grant (30770718) from the National Natural Science Foundation of China and the grants (KSCX2-2-03 and KSCX2-EW-J-8) from the Chinese Academy of Sciences.
WOS IDWOS:000290463100014
Citation statistics
Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/8466
Collection健康与遗传心理学研究室
Corresponding AuthorLin, WJ (reprint author), Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, 4A Datun Rd, Beijing 100101, Peoples R China.
Affiliation1.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing 100101, Peoples R China
2.Chinese Acad Sci, Inst Psychol, Brain Behav Res Ctr, Beijing 100101, Peoples R China
3.Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China
First Author AffilicationKey Laboratory of Mental Health, CAS
Recommended Citation
GB/T 7714
Wang, Donglin,Lin, Wenjuan,Pan, Yuqin,et al. Chronic blockade of glucocorticoid receptors by RU486 enhances lipopolysaccharide-induced depressive-like behaviour and cytokine production in rats[J]. BRAIN BEHAVIOR AND IMMUNITY,2011,25(4):706-714.
APA Wang, Donglin.,Lin, Wenjuan.,Pan, Yuqin.,Kuang, Xueying.,Qi, Xiaoli.,...&Lin, WJ .(2011).Chronic blockade of glucocorticoid receptors by RU486 enhances lipopolysaccharide-induced depressive-like behaviour and cytokine production in rats.BRAIN BEHAVIOR AND IMMUNITY,25(4),706-714.
MLA Wang, Donglin,et al."Chronic blockade of glucocorticoid receptors by RU486 enhances lipopolysaccharide-induced depressive-like behaviour and cytokine production in rats".BRAIN BEHAVIOR AND IMMUNITY 25.4(2011):706-714.
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