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.
Program in Neuroscience, Howard Hughes Medical Institute, Children's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
S C
SC
Weninger
A J
AJ
Dunn
L J
LJ
Muglia
P
P
Dikkes
K A
KA
Miczek
A H
AH
Swiergiel
C W
CW
Berridge
J A
JA
Majzoub
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