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Limbic corticotropin-releasing hormone receptor 1 mediates anxiety-related behavior and hormonal adaptation to stress

Item Type:Article
Title:Limbic corticotropin-releasing hormone receptor 1 mediates anxiety-related behavior and hormonal adaptation to stress
Creators Name:Mueller, M.B. and Zimmermann, S. and Sillaber, I. and Hagemeyer, T.P. and Deussing, J.M. and Timpl, P. and Kormann, M.S.D. and Droste, S.K. and Kuehn, R. and Reul, J.M.H.M. and Holsboer, F. and Wurst, W.
Abstract:Corticotropin-releasing hormone (CRH) is centrally involved in coordinating responses to a variety of stress-associated stimuli. Recent clinical data implicate CRH in the pathophysiology of human affective disorders. To differentiate the CNS pathways involving CRH and CRH receptor 1 (Crhr1) that modulate behavior from those that regulate neuroendocrine function, we generated a conditional knockout mouse line (Crhr1(loxP/loxP)Camk2a-cre) in which Crhr1 function is inactivated postnatally in anterior forebrain and limbic brain structures, but not in the pituitary. This leaves the hypothalamic-pituitary-adrenocortical (HPA) system intact. Crhr1(loxP/loxP)Camk2a-cre mutants showed reduced anxiety, and the basal activity of their HPA system was normal. In contrast to Crhr1 null mutants, conditional mutants were hypersensitive to stress corticotropin and corticosterone levels remained significantly elevated after stress. Our data clearly show that limbic Crhr1 modulates anxiety-related behavior and that this effect is independent of HPA system function. Furthermore, we provide evidence for a new role of limbic Crhr1 in neuroendocrine adaptation to stress.
Keywords:Animal Behavior, Anxiety Disorders, Corticotropin-Releasing Hormone, Corticotropin-Releasing Hormone Receptors, Hypothalamo-Hypophyseal System, Knockout Mice, Limbic System, Messenger RNA, Mineralocorticoid Receptors, Mutation, Neural Pathways, Physiological Adaptation, Physiological Stress, Pituitary-Adrenal System, Prosencephalon, Animals, Mice
Source:Nature Neuroscience
ISSN:1097-6256
Publisher:Nature Publishing Group (U.S.A.)
Volume:6
Number:10
Page Range:1100-1107
Date:October 2003
Official Publication:https://doi.org/10.1038/nn1123
PubMed:View item in PubMed

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