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Corticotropin-Releasing Factor in the Norepinephrine Nucleus, Locus Coeruleus, Facilitates Behavioral Flexibility
Snyder, Kevin2; Wang, Wei-Wen3; Han, Rebecca2; McFadden, Kile1; Valentino, Rita J.1; Valentino, RJ (reprint author), Childrens Hosp Philadelphia, Abramson Pediat Res Ctr 402D, Dept Anesthesiol & Crit Care Med, Philadelphia, PA 19104 USA.
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摘要Corticotropin-releasing factor (CRF), the stress-related neuropeptide, acts as a neurotransmitter in the brain norepinephrine nucleus, locus coeruleus (LC), to activate this system during stress. CRF shifts the mode of LC discharge from a phasic to a high tonic state that is thought to promote behavioral flexibility. To investigate this, the effects of CRF administered either intracerebroventricularly (30-300 ng, i.c.v.) or directly into the LC (intra-LC; 2-20 ng) were examined in a rat model of attentional set shifting. CRF differentially affected components of the task depending on dose and route of administration. Intracerebroventricular CRF impaired intradimensional set shifting, reversal learning, and extradimensional set shifting (EDS) at different doses. In contrast, intra-LC CRF did not impair any aspect of the task. The highest dose of CRF (20 ng) facilitated reversal learning and the lowest dose (2 ng) improved EDS. The dose-response relationship for CRF on EDS performance resembled an inverted U-shaped curve with the highest dose having no effect. Intra-LC CRF also elicited c-fos expression in prefrontal cortical neurons with an inverted U-shaped dose-response relationship. The number of c-fos profiles was positively correlated with EDS performance. Given that CRF excites LC neurons, the ability of intra-LC CRF to activate prefrontal cortical neurons and facilitate EDS is consistent with findings implicating LC-norepinephrine projections to medial prefrontal cortex in this process. Importantly, the results suggest that CRF release in the LC during stress facilitates shifting of attention between diverse stimuli in a dynamic environment so that the organism can adapt an optimal strategy for coping with the challenge. Neuropsychopharmacology (2012) 37, 520-530; doi:10.1038/npp.2011.218; published online 12 October 2011
关键词stress set shifting behavioral flexibility prefrontal cortex reversal learning norepinephrine
学科领域Cognitive Neuroscience
2012
语种英语
发表期刊NEUROPSYCHOPHARMACOLOGY
ISSN0893-133X
卷号37期号:2页码:520-530
期刊论文类型Article
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收录类别SCI
项目简介This research was supported by PHS Grant MH40008, DA09082, MH14654 (KS), ARO 58077-LS-DRP (S Bhatnagar), National Basic Research Program of China (2007CB512306), Institute of Psychology Beijing (09CX133013), and the Chinese Academy of Sciences (KSCX2-EW-J-8). We acknowledge the assistance of Rosemary Trumbull and statistical consultation with Nayla Chaijale.
WOS记录号WOS:000298342500022
资助机构PHS [MH40008, DA09082, MH14654] ; ARO [58077-LS-DRP] ; National Basic Research Program of China [2007CB512306] ; Institute of Psychology Beijing [09CX133013] ; Chinese Academy of Sciences [KSCX2-EW-J-8]
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被引频次:105[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.psych.ac.cn/handle/311026/11456
专题中国科学院心理健康重点实验室
通讯作者Valentino, RJ (reprint author), Childrens Hosp Philadelphia, Abramson Pediat Res Ctr 402D, Dept Anesthesiol & Crit Care Med, Philadelphia, PA 19104 USA.
作者单位1.Childrens Hosp Philadelphia, Abramson Pediat Res Ctr 402D, Dept Anesthesiol & Crit Care Med, Philadelphia, PA 19104 USA
2.Univ Penn, Philadelphia, PA 19104 USA
3.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing 100101, Peoples R China
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Snyder, Kevin,Wang, Wei-Wen,Han, Rebecca,et al. Corticotropin-Releasing Factor in the Norepinephrine Nucleus, Locus Coeruleus, Facilitates Behavioral Flexibility[J]. NEUROPSYCHOPHARMACOLOGY,2012,37(2):520-530.
APA Snyder, Kevin,Wang, Wei-Wen,Han, Rebecca,McFadden, Kile,Valentino, Rita J.,&Valentino, RJ .(2012).Corticotropin-Releasing Factor in the Norepinephrine Nucleus, Locus Coeruleus, Facilitates Behavioral Flexibility.NEUROPSYCHOPHARMACOLOGY,37(2),520-530.
MLA Snyder, Kevin,et al."Corticotropin-Releasing Factor in the Norepinephrine Nucleus, Locus Coeruleus, Facilitates Behavioral Flexibility".NEUROPSYCHOPHARMACOLOGY 37.2(2012):520-530.
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