Mechanisms of Alcohol Effects on Sleep

酒精影响睡眠的机制

• 批准号: 6710196
• 负责人: STEVEN M SIMASKO
• 金额: $ 29.36万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6710196
• 关键词: alcohols; biological models; biological signal transduction; growth hormone releasing hormone; hormone inhibitor; hormone receptor; hypothalamic pituitary axis; laboratory rat; messenger RNA; receptor expression; sleep; somatostatin

DESCRIPTION (provided by applicant): the long-term objective of this research is to understand the biological basis for the disruptive effect of alcohol on sleep. The specific goal of this project is to test the hypothesis that alcohol-induced alterations in sleep are mediated by a disruption of the role of growth hormone releasing hormone (GHRH) in regulating normal sleep. The basis for this hypothesis is that it is well established that alcohol can disrupt the normal control of the somatotropic axis, primarily at the hypothalamic level, and that GHRH, a key hypothalamic regulator of the somatotropic axis, is a humoral agent that has been shown to play an important role in regulating normal sleep. In this project a sophisticated and modern model of sleep research in rats will be used to examine both the acute and chronic effects of alcohol on sleep. This model will then be used to test for alterations in the normal effects of GHRH, a GHRH antagonist, and somatostatin (SS) on sleep during acute and after chronic alcohol exposure. In addition, acute and chronic effects of alcohol in a dwarf rat model in which GHRH receptor signaling is disrupted will be examined. The biological basis for any alteration in the normal actions of these hormones on sleep will be determined in a parallel set of studies in which the effects of acute and chronic alcohol on hypothalamic GHRH, SS, their respective receptors, and the mRNA for each hormone and receptor are determined. Finally, hypothalamic explants will be used to examine the effects of acute and chronic alcohol on GHRH release. Completion of these studies will produce several accomplishments in addition to testing the role of GHRH in alcohol-induced sleep alterations. It will establish a well characterized model in which future studies on the effects of alcohol on other sleep factors can be pursued, and it will provide many biological insights into the disruption of the somatotropic axis by alcohol which will be important for understanding alcohol disturbances in the endocrine somatotropic axis. Finally, if long-term disruptions in sleep by alcohol are due to alterations in normal sleep regulation by GHRH, the results from these studies will illuminate potential therapeutic interventions that could restore normal sleep regulation. Such interventions could prove to be a useful adjunct to treat recovering alcoholics since prolonged sleep disturbances are a predicting factor for relapse into drinking behavior.

描述（申请人提供）：本研究的长期目标 是为了了解酒精对大脑的破坏性影响的生物学基础， 睡吧这个项目的具体目标是测试假设， 酒精引起的睡眠改变是通过破坏 生长激素释放激素（GHRH）调节正常睡眠。的 这一假设的基础是，酒精可以 破坏生长激素轴的正常控制，主要是在 下丘脑水平，以及GHRH，一种关键下丘脑调节因子， 促生长轴是一种体液因子，已被证明在 调节正常睡眠。在这个项目中， 大鼠睡眠研究模型将用于检查急性和 酒精对睡眠的慢性影响该模型将用于测试 GHRH（一种GHRH拮抗剂）和生长抑素正常作用的改变 (SS)在急性和慢性酒精暴露后的睡眠。此外，本发明还提供了一种方法， 酒精对侏儒大鼠模型的急性和慢性影响， 将检查受体信号传导被破坏。任何生物学基础 这些激素对睡眠的正常作用的改变将被确定 在一组平行的研究中，急性和慢性酒精的影响 对下丘脑GHRH、SS及其各自的受体和各自的mRNA的影响 测定激素和受体。最后，将下丘脑外植体 用于检查急性和慢性酒精对GHRH释放的影响。 完成这些研究将产生若干成就， 测试GHRH在酒精诱导的睡眠改变中的作用。它将 建立一个良好的表征模型，其中未来的研究的影响， 酒精对其他睡眠因素可以追求，它将提供许多 酒精对生长激素轴的破坏的生物学见解 这对于了解酒精对内分泌系统的影响很重要 促体细胞轴最后，如果酒精对睡眠的长期干扰 由于GHRH改变了正常的睡眠调节， 研究将阐明潜在的治疗干预， 正常的睡眠调节。这种干预可能被证明是一种有益的辅助手段 因为长期的睡眠障碍是一种 复发饮酒行为的预测因素。