Mechanisms of Alcohol Effects on Sleep

描述(申请人提供)：本研究的长期目标 是为了了解酒精对人体的破坏性影响的生物学基础 睡吧。这个项目的具体目标是检验这样一个假设 酒精引起的睡眠改变是由这种作用的破坏所介导的 生长激素释放激素(GHRH)调节正常睡眠。这个 这一假说的基础是酒精可以 扰乱对促生长轴的正常控制，主要是在 下丘脑水平，以及GHRH，下丘脑的关键调节因子 促生长轴，是一种已被证明发挥重要作用的体液因子 在调节正常睡眠方面的作用。在这个项目中，一个复杂而现代的 将使用大鼠睡眠研究模型来检查急性和非急性睡眠 酒精对睡眠的慢性影响。然后，该模型将用于测试 生长激素释放激素拮抗剂GHRH和生长抑素正常作用的改变 (SS)急性酒精暴露期间和慢性酒精暴露后的睡眠。此外, 酒精对GHRH致侏儒大鼠模型的急性和慢性影响 受体信号被扰乱将被检查。任何生物行为的生物学基础 这些荷尔蒙在睡眠中正常作用的变化将被确定。 在一组平行的研究中，急性和慢性酒精的影响 下丘脑GHRH、SS及其受体及其mRNA的表达 测定激素和受体。最后，下丘脑的外植体将 用于检测急性和慢性酒精对GHRH释放的影响。 这些研究的完成将产生几项成就，此外 测试GHRH在酒精引起的睡眠改变中的作用。会的 建立一个具有良好特征的模型，在该模型中，未来对 酒精对其他睡眠因素的影响是可以追求的，它将提供许多 酒精扰乱促生长轴的生物学研究 这对了解酒精在内分泌中的紊乱很重要 躯体运动轴。最后，如果酒精对睡眠的长期干扰是 由于GHRH对正常睡眠调节的改变，这些结果 研究将阐明潜在的治疗干预措施可以恢复 正常的睡眠规则。这些干预措施可能会被证明是一个有用的辅助工具。 治疗正在康复的酗酒者，因为长期的睡眠障碍是一种 饮酒行为复发的预测因素。

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.