Increase in Corticotropin-Releasing Hormone (CRH) in the Central Nervous System Mediates Stressor-Induced Sleep Alterations

Abstract

Objectives. Our previous results demonstrated that an acute stressor increased wakefulness and reduced rapid eye movement sleep (REMS), without altering slow wave sleep (SWS); furthermore, central administration of corticotropin-releasing hormone (CRH) antagonist astressin blocked the increase in wakefulness after stressor. However, stressor in rats well habituated to handling and injection procedures did not alter circulating corticosterone concentrations. Based upon those observations, we hypothesized that under those conditions, central CRH, but not the hypothalamic-pituitary-adrenal (HPA) axis, mediates sleep alterations after stressor. Here we provide further evidence of the increase in prepro-CRH mRNA in the CNS after stressor. Methods. Naive rats were subjected to a 1-hour period of physical restraint. The expression of prepro-CRH mRNA from hippocampus, brainstem, hypothalamus and cortex were measured by ribonucleus protection assay. Total plasma corticosterone was determined by radioimmunoassay. Results. The expression of prepro-CRH mRNA in hypothalamus and brainstem, but not in cortex and hippocampus, had increased after 1-hour of restraint and after 1-hour of recovery postrestraint. Circulating corticosterone concentration rose during the 1-hour period of restraint; however, it returned to its basal concentration after the one-hour recovery period post-restraint. Conclusions. These results suggest that the continuous increase in central CRH, rather than HPA axis activity, mediates the alteration in sleep-wake activity of rats exposed to acute physical restraint. ( Mid Taiwan J Med 2004;9:80-6