Sleep is altered in response to psychological stressors; the precise mechanisms whereby such alterations occur are not known. Behavioral responses to most stressors include increased arousal and waking. We hypothesize that corticotropin-releasing hormone (CRH) is a mediator of waking, particularly that which follows periods of exposure to acute stressors. The behavioral, physiological, electrophysiological, and anatomical data currently available support this hypothesis. We have obtained new experimental evidence supporting the hypothesis that CRH is involved in physiological regulation of waking; Lewis/N rats, a strain that exhibits reduced synthesis and secretion of CRH relative to histocompatible Fischer 344/N (F344/N) or Sprague-Dawley rats, exhibit reduced amounts of spontaneous waking compared to these other two strains. Our central hypothesis will be tested within the context of two specific aims. Specifically, we will determine 1) the extent to which CRN contributes to increased wakefulness that follows exposure to acute stressors, by subjecting rats to a cage-switch stressor, in the presence or absence of CRH antagonists. We will also 2) ascertain the potential contribution of CRH to physiological regulation of waking by administering CRH antagonists into normal animals, and by exploiting the """"""""natural"""""""" model of the Lewis/N, F344/N, and Sprague-Dawley rats. We will use rats instrumented with EEG electrodes, a chronic ventricular guide cannula, a thermistor to monitor brain temperature, and, in some cases a jugular cannula to allow blood sampling from freely behaving animals. Waking and sleep will be determined by visual inspection of electrophysiological records that have been recorded by a computerized data acquisition system. Upon completion of these experiments we will know the extent to which CRH contributes to stressor-induced alterations in waking, mechanisms of action where, by such responses may be mediated, and the role of CRH in normal patterning of waking and sleep.
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