Pituitary CRH receptor blockade reduces waking in the rat

We have previously hypothesized that corticotropin-releasing hormone (CRH) is involved in the regulation of physiological waking. Central administration of CRH receptor antagonists reduces spontaneous waking in the rat. Some of the responses to central administration of CRH receptor antagonists may be mediated by mechanisms involving the hypothalamic-pituitary-adrenal axis, either by direct actions on the hypothalamus or by actions at the level of the pituitary due to leakage of the antagonists from the cerebrospinal fluid to blood. To further clarify the role of the hypothalamic-pituitary-adrenal axis as a mediator of responses to CRH receptor blockade, we administered intravenously into freely behaving rats in their home recording cages two specific CRH receptor antagonists, astressin or alpha-helical CRH, and determined subsequent changes in waking and sleep. Our results indicate that both antagonists reduce spontaneous waking, but with different time courses. Astressin, a potent antagonist of pituitary CRH receptors, reduces waking during postinjection hours 9-10, whereas high doses of alpha-helical CRH reduce waking only during the first postinjection hour. These results indicate that some effects of CRH on sleep-wake behavior may be meditated by pituitary CRH receptors.