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A role for the extracellular signal-regulated kinase signal pathway in depressive-like behavior
Qi, Xiaoli; Lin, Wenjuan; Wang, Donglin; Pan, Yuqin; Wang, Weiwen; Sun, Meng; W. J. Lin
2009-05-16
Source PublicationBEHAVIOURAL BRAIN RESEARCH
ISSN0166-4328
SubtypeArticle
Volume199Issue:2Pages:203-209
AbstractOur recent research demonstrates that the extracellular signal-regulated kinase (ERK) signal pathway is impaired in depressed animals, and such disruption is effectively reversed following antidepressant treatment. These results indicate that the ERK pathway may participate in the molecular mechanism of depression. To provide direct evidence for the potential role of the ERK pathway in depression, the present study using a sub-chronic regimen of ERK inhibition investigated the disparate role for the ERK cascade in two specific brain areas, the dorsal hippocampus (dHP) and the medial prefrontal cortex (mPFC). in the pathophysiology of depressive-like behavior. Rats were bilaterally implanted with cannulas in the dHP or mPFC and were microinjected with U0126, a specific inhibitor of ERK upstream activator, or vehicle for 7 consecutive days. The behavioral effects of the ERK pathway inhibition were examined in the open field, elevated plus maze, and saccharin preference test. The results showed that the inhibition of the ERK pathway in dHP resulted in anhedonia and anxiety-like behavior, and the ERK pathway inhibition in the mPFC induced anhedonia and locomotor impairment in rats. The phosphorylation of the cyclic AMP-responsive-element-binding protein (CREB) was decreased following the ERK pathway inhibition either in dHP or mPFC. These findings demonstrate that the ERK pathway in either the dHP or mPFC participates in the pathophysiology of the depressive-like behavior, and may have pivotal role in human depression.; Our recent research demonstrates that the extracellular signal-regulated kinase (ERK) signal pathway is impaired in depressed animals, and such disruption is effectively reversed following antidepressant treatment. These results indicate that the ERK pathway may participate in the molecular mechanism of depression. To provide direct evidence for the potential role of the ERK pathway in depression, the present study using a sub-chronic regimen of ERK inhibition investigated the disparate role for the ERK cascade in two specific brain areas, the dorsal hippocampus (dHP) and the medial prefrontal cortex (mPFC). in the pathophysiology of depressive-like behavior. Rats were bilaterally implanted with cannulas in the dHP or mPFC and were microinjected with U0126, a specific inhibitor of ERK upstream activator, or vehicle for 7 consecutive days. The behavioral effects of the ERK pathway inhibition were examined in the open field, elevated plus maze, and saccharin preference test. The results showed that the inhibition of the ERK pathway in dHP resulted in anhedonia and anxiety-like behavior, and the ERK pathway inhibition in the mPFC induced anhedonia and locomotor impairment in rats. The phosphorylation of the cyclic AMP-responsive-element-binding protein (CREB) was decreased following the ERK pathway inhibition either in dHP or mPFC. These findings demonstrate that the ERK pathway in either the dHP or mPFC participates in the pathophysiology of the depressive-like behavior, and may have pivotal role in human depression. (C) 2008 Elsevier B.V. All rights reserved.
KeywordERK CREB Hippocampus Prefrontal cortex U0126 Depression
Subject Area生理心理学/生物心理学
Indexed BySCI
Language英语
WOS IDWOS:000264953700005
Citation statistics
Cited Times:49[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/5143
Collection中国科学院心理研究所回溯数据库(1956-2010)
Corresponding AuthorW. J. Lin
AffiliationChinese Acad Sci, Key Lab Mental Hlth, Inst Psychol, Beijing 100101, Peoples R China
First Author AffilicationKey Laboratory of Mental Health, CAS
Recommended Citation
GB/T 7714
Qi, Xiaoli,Lin, Wenjuan,Wang, Donglin,et al. A role for the extracellular signal-regulated kinase signal pathway in depressive-like behavior[J]. BEHAVIOURAL BRAIN RESEARCH,2009,199(2):203-209.
APA Qi, Xiaoli.,Lin, Wenjuan.,Wang, Donglin.,Pan, Yuqin.,Wang, Weiwen.,...&W. J. Lin.(2009).A role for the extracellular signal-regulated kinase signal pathway in depressive-like behavior.BEHAVIOURAL BRAIN RESEARCH,199(2),203-209.
MLA Qi, Xiaoli,et al."A role for the extracellular signal-regulated kinase signal pathway in depressive-like behavior".BEHAVIOURAL BRAIN RESEARCH 199.2(2009):203-209.
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