title: Limbic corticotropin-releasing hormone receptor 1 mediates anxiety-related behavior and hormonal adaptation to stress.
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.
authors.affiliation: Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, Munich 80804, Germany.
authors.forename: Marianne B
authors.initials: MB
authors.lastname: Müller
authors.forename: Stephan
authors.initials: S
authors.lastname: Zimmermann
authors.forename: Inge
authors.initials: I
authors.lastname: Sillaber
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Hagemeyer
authors.forename: Jan M
authors.initials: JM
authors.lastname: Deussing
authors.forename: Peter
authors.initials: P
authors.lastname: Timpl
authors.forename: Michael S D
authors.initials: MS
authors.lastname: Kormann
authors.forename: Susanne K
authors.initials: SK
authors.lastname: Droste
authors.forename: Ralf
authors.initials: R
authors.lastname: Kühn
authors.forename: Johannes M H M
authors.initials: JM
authors.lastname: Reul
authors.forename: Florian
authors.initials: F
authors.lastname: Holsboer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D001008:Anxiety Disorders / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology; D008032:Limbic System / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D010913:Pituitary-Adrenal System / Q000378:metabolism / Q000503:physiopathology; D016548:Prosencephalon / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000172:deficiency* / Q000235:genetics; D018161:Receptors, Mineralocorticoid / Q000235:genetics; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D000099052:CRF Receptor, Type 1
chemical_list: D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D018161:Receptors, Mineralocorticoid; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone