title: Assessing behavioural effects of chronic HPA axis activation using conditional CRH-overexpressing mice.
abstract: The corticotropin-releasing hormone (CRH) and its cognate receptors have been implicated in the pathophysiology of stress-related disorders. Hypersecretion of central CRH and elevated glucocorticoid levels, as a consequence of impaired feedback control, have been shown to accompany mood and anxiety disorders. However, a clear discrimination of direct effects of centrally hypersecreted CRH from those resulting from HPA axis activation has been difficult. Applying a conditional strategy, we have generated two conditional CRH-overexpressing mouse lines: CRH-COE                         (                            Del                         ) mice overexpress CRH throughout the body, while CRH-COE                         (                            APit                         ) mice selectively overexpress CRH in the anterior and intermediate lobe of the pituitary. Both mouse lines show increased basal plasma corticosterone levels and consequently develop signs of Cushing's syndrome. However, while mice ubiquitously overexpressing CRH exhibited increased anxiety-related behaviour, overexpression of CRH in the pituitary did not produce alterations in emotional behaviour. These results suggest that chronic hypercorticosteroidism alone is not sufficient to alter anxiety-related behaviour but rather that central CRH hyperdrive on its own or in combination with elevated glucocorticoids is responsible for the increase in anxiety-related behaviour. In conclusion, the generated mouse lines represent valuable animal models to study the consequences of chronic CRH overproduction and HPA axis activation.
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Dedic
authors.forename: Chadi
authors.initials: C
authors.lastname: Touma
authors.forename: Cristoph P
authors.initials: CP
authors.lastname: Romanowski
authors.forename: Marcel
authors.initials: M
authors.lastname: Schieven
authors.forename: Claudia
authors.initials: C
authors.lastname: Kühne
authors.forename: Martin
authors.initials: M
authors.lastname: Ableitner
authors.forename: Ailing
authors.initials: A
authors.lastname: Lu
authors.forename: Florian
authors.initials: F
authors.lastname: Holsboer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
authors.forename: Mayumi
authors.initials: M
authors.lastname: Kimura
authors.forename: Jan M
authors.initials: JM
authors.lastname: Deussing
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000473:pathology; D001522:Behavior, Animal / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D010902:Pituitary Gland / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism* / Q000473:pathology*; D012895:Sleep, REM
chemical_list: D003346:Corticotropin-Releasing Hormone