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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29MH052275-03
Application #
2460371
Study Section
Clinical Neuroscience and Biological Psychopathology Review Committee (CNBP)
Project Start
1995-08-01
Project End
2000-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Psychiatry
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555
Chang, Fang-Chia; Opp, Mark R (2004) A corticotropin-releasing hormone antisense oligodeoxynucleotide reduces spontaneous waking in the rat. Regul Pept 117:43-52
Chang, Fang-Chia; Opp, Mark R (2002) Role of corticotropin-releasing hormone in stressor-induced alterations of sleep in rat. Am J Physiol Regul Integr Comp Physiol 283:R400-7
Rose, M; Sanford, A; Thomas, C et al. (2001) Factors altering the sleep of burned children. Sleep 24:45-51
Opp, M R; Imeri, L (2001) Rat strains that differ in corticotropin-releasing hormone production exhibit different sleep-wake responses to interleukin 1. Neuroendocrinology 73:272-84
Chang, F C; Opp, M R (2000) IL-1 is a mediator of increases in slow-wave sleep induced by CRH receptor blockade. Am J Physiol Regul Integr Comp Physiol 279:R793-802
Opp, M R; Imeri, L (1999) Sleep as a behavioral model of neuro-immune interactions. Acta Neurobiol Exp (Wars) 59:45-53
Chang, F C; Opp, M R (1999) Pituitary CRH receptor blockade reduces waking in the rat. Physiol Behav 67:691-6
Chang, F C; Opp, M R (1998) Blockade of corticotropin-releasing hormone receptors reduces spontaneous waking in the rat. Am J Physiol 275:R793-802
Opp, M R; Toth, L A (1998) Somnogenic and pyrogenic effects of interleukin-1beta and lipopolysaccharide in intact and vagotomized rats. Life Sci 62:923-36
Opp, M R; Toth, L A (1997) Circadian modulation of interleukin-1-induced fever in intact and vagotomized rats. Ann N Y Acad Sci 813:435-6

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