Stress-induced behaviors require the corticotropin-releasing hormone (CRH) receptor, but not CRH.
Corticotropin-releasing hormone (CRH) is a central regulator of the hormonal stress response, causing stimulation of corticotropin and glucocorticoid secretion. CRH is also widely believed to mediate stress-induced behaviors, implying a broader, integrative role for the hormone in the psychological stress response. Mice lacking the CRH gene exhibit normal stress-induced behavior that is specifically blocked by a CRH type 1 receptor antagonist. The other known mammalian ligand for CRH receptors is urocortin. Normal and CRH-deficient mice have an identical distribution of urocortin mRNA, which is confined to the region of the Edinger-Westphal nucleus, and is absent from regions known to mediate stress-related behaviors. Since the Edinger-Westphal nucleus is not known to project to any brain regions believed to play a role in anxiety-like behavior, an entirely different pathway must be postulated for urocortin in the Edinger-Westphal nucleus to mediate these behaviors in CRH-deficient mice. Alternatively, an unidentified CRH-like molecule other than CRH or urocortin, acting through the CRH receptors in brain regions believed to mediate stress-induced behaviors, may mediate the behavioral response to stress, either alone or in concert with CRH.
Weninger
S C
SC
Program in Neuroscience, Howard Hughes Medical Institute, Children's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
Dunn
A J
AJ
Muglia
L J
LJ
Dikkes
P
P
Miczek
K A
KA
Swiergiel
A H
AH
Berridge
C W
CW
Majzoub
J A
JA
D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D002552:Cerebral Ventricles / Q000502:physiology; D003216:Conditioning, Operant / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D003433:Crosses, Genetic; D004597:Electroshock; D005239:Fear; D005260:Female; D005786:Gene Expression Regulation; D007276:Injections, Intraventricular; D007858:Learning / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology*; D010146:Pain / Q000235:genetics / Q000503:physiopathology*; D011743:Pyrimidines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000502:physiology*; D012054:Reinforcement, Psychology; D013315:Stress, Psychological; D014158:Transcription, Genetic; D054832:Urocortins
C101628:CP 154526; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D003346:Corticotropin-Releasing Hormone