HUMORAL REGULATION OF WAKING--THE ROLE OF CRH

清醒时的体液调节--CRH 的作用

• 批准号: 2460371
• 负责人: MARK R OPP
• 金额: $ 9.89万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2460371
• 关键词: arousal; blood chemistry; body temperature; brain electrical activity; circadian rhythms; corticosterone; corticotropin releasing factor; electroencephalography; genetic strain; hormone regulation /control mechanism; hypothalamic pituitary axis; laboratory rat; neuroendocrine system; pituitary adrenal axis; sleep; stressor; wakefulness

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.

睡眠是对心理压力的反应而改变；准确的 发生这种变化的机制尚不清楚。行为 对大多数压力源的反应包括唤醒和清醒。我们 假设促肾上腺皮质激素释放激素(CRH)是一种 醒着，尤其是在暴露于急性呼吸道感染之后 压力源。行为、生理、电生理和 目前可用的解剖学数据支持这一假设。我们有 获得了新的实验证据，支持CRH是 参与清醒的生理调节；Lewis/N大鼠，一种品系 表现出CRH的合成和分泌相对于 组织相容性Fischer 344/N(F344/N)或Spraogue-Dawley大鼠 与其他两种菌株相比，自发性清醒的数量减少了。 我们的中心假设将在两个特定的背景下进行检验 目标。具体地说，我们将确定1)CRN的程度 导致暴露在急性呼吸道感染后的清醒程度增加 应激源，通过将大鼠置于笼子开关应激源，在 或缺乏CRH拮抗剂。我们还将确定潜在的 促肾上腺皮质激素释放激素在清醒生理调节中的作用 CRH拮抗剂进入正常动物，并通过利用“自然”模型 Lewis/N、F344/N和Spraogue-Dawley大鼠。我们将使用老鼠 配备脑电电极的慢性脑室导管术 用来监测大脑温度的热敏电阻，在某些情况下还能监测颈静脉 允许从行为自由的动物身上采集血液的插管。醒着的时候 睡眠将通过电生理的视觉检查来确定 已由计算机化数据采集系统记录的记录。 在这些实验完成后，我们将知道CRH在多大程度上 促进应激源诱导的觉醒改变，机制 可以通过这种反应来调节的行动，以及CRH在 醒着和睡着的正常模式。