Mechanisms of Alcohol Effects on Sleep

酒精影响睡眠的机制

• 批准号: 6470788
• 负责人: STEVEN M SIMASKO
• 金额: $ 29.33万
• 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/6470788
• 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（由申请人提供）：这项研究的长期目标 是了解酒精对破坏性作用的生物学基础 睡觉。该项目的具体目标是检验以下假设 酒精诱导的睡眠改变是由该角色的中断介导的 生长激素释放激素（GHRH）在调节正常睡眠中。这 这一假设的基础是，酒精可以很好地确定 破坏对体轴的正常控制，主要是在 下丘脑水平和GHRH，是关键的下丘脑调节剂 种子轴是一种体液剂，已被证明发挥了重要的作用 调节正常睡眠的作用。在这个项目中，一个复杂而现代的 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。然后将使用此模型测试 GHRH拮抗剂和生长抑素GHRH的正常作用的改变 （SS）在急性和慢性酒精暴露后睡眠。此外， 酒精在矮人大鼠模型中的急性和慢性作用，其中GHRH 受体信号被干扰将被检查。任何生物学基础 这些激素对睡眠的正常作用的改变将确定 在一组急性和慢性酒精的影响的平行研究中 在下丘脑GHRH，SS，其各自的受体和mRNA上 测定激素和受体。最后，下丘脑外植体将是 用于检查急性和慢性酒精对GHRH释放的影响。 这些研究的完成还将产生几个成就 测试GHRH在酒精引起的睡眠改变中的作用。会 建立一个表征良好的模型，在该模型中，未来研究 可以追求其他睡眠因素的酒精，它将提供许多 生物学洞察力对饮酒轴破坏的破坏 这对于理解内分泌中的酒精疾病很重要 种子轴。最后，如果酒精的长期睡眠干扰是 由于GHRH的正常睡眠调节改变，这些结果 研究将阐明可以恢复的潜在治疗干预措施 正常的睡眠调节。这种干预措施可能被证明是有用的辅助 治疗康复的酗酒者，因为长时间的睡眠障碍是 预测复发到饮酒行为的因素。