Blockade of corticotropin-releasing hormone receptors reduces spontaneous waking in the rat

Am J Physiol. 1998 Sep;275(3):R793-802. doi: 10.1152/ajpregu.1998.275.3.R793.


We have previously hypothesized that corticotropin-releasing hormone (CRH) is involved in the regulation of physiological waking. To further elucidate this role for CRH, we administered intracerebroventricularly into rats two specific CRH-receptor antagonists, alpha-helical CRH-(9-41) (alpha-hCRH) or astressin, and determined changes in electroencephalogram-defined waking and sleep. Our results indicate that both of these receptor antagonists reduce the amount of time spent awake in a dose-related manner when administered before the dark period of the light-dark cycle. However, the time courses for these effects differ between antagonists; effective doses of alpha-hCRH reduce waking during the first 2 h postinjection, whereas effective doses of astressin reduce waking during postinjection hours 7-12. In contrast to dark-onset administrations, the amount of waking is not altered by either CRH-receptor antagonist when administered before the light period. These results support our hypothesis that CRH contributes to the regulation of physiological waking, since interfering with the binding of CRH to its receptor reduces spontaneous waking.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Corticotropin-Releasing Hormone / administration & dosage
  • Corticotropin-Releasing Hormone / antagonists & inhibitors
  • Corticotropin-Releasing Hormone / pharmacology
  • Corticotropin-Releasing Hormone / physiology*
  • Hormone Antagonists / pharmacology
  • Injections, Intraventricular
  • Kinetics
  • Male
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacology
  • Photoperiod
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors*
  • Receptors, Corticotropin-Releasing Hormone / physiology
  • Wakefulness / drug effects
  • Wakefulness / physiology*


  • Hormone Antagonists
  • Peptide Fragments
  • Receptors, Corticotropin-Releasing Hormone
  • alpha helical corticotropin-releasing hormone
  • astressin
  • Corticotropin-Releasing Hormone