Mechanisms of Alcohol Effects on Sleep

描述（由申请人提供）：本研究的长期目标

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.