Impaired stress response and reduced anxiety in mice lacking a functional corticotropin-releasing hormone receptor 1

P Timpl, R Spanagel, I Sillaber, A Kresse, J M Reul, G K Stalla, V Blanquet, T Steckler, F Holsboer, W Wurst

Research output: Contribution to journalArticle (Academic Journal)peer-review

795 Citations (Scopus)

Abstract

Corticotropin-releasing hormone (CRH) is a potent mediator of endocrine, autonomic, behavioural and immune responses to stress, and has been implicated in the stress-like and other aversive consequences of drug abuse, such as withdrawal from alcohol. Two CRH receptors, Crhr1 and Crhr2, have been identified in the mouse. Crhr1 is highly expressed in the anterior pituitary, neocortex, hippocampus, amygdala and cerebellum, and activation of this receptor stimulates adenylate cyclase. Here we show that in mice lacking Crhr1, the medulla of the adrenal gland is atrophied and stress-induced release of adrenocorticotropic hormone (ACTH) and corticosterone is reduced. The homozygous mutants exhibit increased exploratory activity and reduced anxiety-related behaviour under both basal conditions and following alcohol withdrawal. Our results demonstrate a key role of the Crhr1 receptor in mediating the stress response and anxiety-related behaviour.

Original languageEnglish
Pages (from-to)162-6
Number of pages5
JournalNature Genetics
Volume19
Issue number2
DOIs
Publication statusPublished - Jun 1998

Keywords

  • Adrenocorticotropic Hormone
  • Animals
  • Anxiety
  • Cells, Cultured
  • Corticosterone
  • Ethanol
  • In Situ Hybridization
  • Mice
  • Mice, Knockout
  • Pituitary Gland
  • Receptors, Corticotropin-Releasing Hormone
  • Stress, Physiological
  • Substance Withdrawal Syndrome

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