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Am J Physiol Regul Integr Comp Physiol 275: R793-R802, 1998;
0363-6119/98 $5.00
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Vol. 275, Issue 3, R793-R802, September 1998

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

Fang-Chia Chang1 and Mark R. Opp1,2

1 Neuroscience Graduate Program and 2 Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, Galveston, Texas 77550-0431

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.

sleep; hypothalamic-pituitary-adrenal axis; astressin; antagonist; partial agonist; stress


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