title: Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress.
abstract: Corticotropin-releasing hormone (Crh) is a critical coordinator of the hypothalamic-pituitary-adrenal (HPA) axis. In response to stress, Crh released from the paraventricular nucleus (PVN) of the hypothalamus activates Crh receptors on anterior pituitary corticotropes, resulting in release of adrenocorticotropic hormone (Acth) into the bloodstream. Acth in turn activates Acth receptors in the adrenal cortex to increase synthesis and release of glucocorticoids. The receptors for Crh, Crhr1 and Crhr2, are found throughout the central nervous system and periphery. Crh has a higher affinity for Crhr1 than for Crhr2, and urocortin (Ucn), a Crh-related peptide, is thought to be the endogenous ligand for Crhr2 because it binds with almost 40-fold higher affinity than does Crh. Crhr1 and Crhr2 share approximately 71% amino acid sequence similarity and are distinct in their localization within the brain and peripheral tissues. We generated mice deficient for Crhr2 to determine the physiological role of this receptor. Crhr2-mutant mice are hypersensitive to stress and display increased anxiety-like behaviour. Mutant mice have normal basal feeding and weight gain, but decreased food intake following food deprivation. Intravenous Ucn produces no effect on mean arterial pressure in the mutant mice.
authors.affiliation: Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, La Jolla, CA
authors.forename: T L
authors.initials: TL
authors.lastname: Bale
authors.forename: A
authors.initials: A
authors.lastname: Contarino
authors.forename: G W
authors.initials: GW
authors.lastname: Smith
authors.forename: R
authors.initials: R
authors.lastname: Chan
authors.forename: L H
authors.initials: LH
authors.lastname: Gold
authors.forename: P E
authors.initials: PE
authors.lastname: Sawchenko
authors.forename: G F
authors.initials: GF
authors.lastname: Koob
authors.forename: W W
authors.initials: WW
authors.lastname: Vale
authors.forename: K F
authors.initials: KF
authors.lastname: Lee
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics*; D001008:Anxiety Disorders / Q000235:genetics; D001522:Behavior, Animal / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000378:metabolism; D004435:Eating / Q000502:physiology; D005260:Female; D005508:Food Deprivation / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D007262:Infusions, Intravenous; D008297:Male; D018782:Maze Learning; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009599:Nitroprusside / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000502:physiology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D013312:Stress, Physiological / Q000235:genetics* / Q000503:physiopathology; D054832:Urocortins; D014665:Vasodilator Agents / Q000494:pharmacology; D015430:Weight Gain / Q000502:physiology
chemical_list: C101531:CRF receptor type 2; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D014665:Vasodilator Agents; D009599:Nitroprusside; D003346:Corticotropin-Releasing Hormone