Rat strain differences suggest a role for corticotropin-releasing hormone in modulating sleep

Abstract

Corticotropin-releasing hormone (CRH) mediates many of the hormonal, behavioral, and autonomic responses to a variety of stressors. There is also evidence suggesting that CRH may be involved in the modulation of physiologic waking. Lewis (LEW) rats possess a hypothalamic gene defect that results in reduced synthesis and secretion of CRH relative to genetically related Fischer 344 (F344) and Sprague-Dawley (Sp-D) rat strains. We therefore hypothesized that LEW rats would spend less time awake, and more time asleep, than either F344 or Sp-D rats. Adult male LEW, F344, and Sp-D rats were surgically provided with electroencephalograph (EEG) recording electrodes, and a thermistor to measure cortical brain temperature [T(cort)]. Additional rats were also provided with a chronic guide cannula directed into a lateral cerebral ventricle. Spontaneous sleep-wake behavior was determined from 48-h recordings of the EEG, T(cort), and body movements from freely behaving, undisturbed rats. Analyses of 48-h recordings from undisturbed animals indicate that LEW rats spend less time awake and more time in slow-wave sleep, relative to the other strains tested. Rapid eye movement sleep did not differ consistently between rat strains. LEW and Sp-D rats exhibit the same degree of waking in response to intracerebroventricular administration of CRH, indicating central mechanisms mediating behavioral responses to exogenously administered CRH are intact in LEW rats. These data provide support for the hypothesis that CRH may be a modulator of waking and sleep.