Neurochemical Substrates of Sleep Homeostasis

睡眠稳态的神经化学底物

• 批准号: 6555777
• 负责人: CYNTHIA M DORSEY
• 金额: $ 39.5万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6555777
• 关键词: bioenergetics; biomarker; clinical research; cocaine; drug abuse; drug withdrawal; electrocardiography; electroencephalography; electromyography; homeostasis; human subject; magnetic resonance imaging; methadone; neurochemistry; nucleoside triphosphate; opiate alkaloid; phospholipids; polysomnography; questionnaires; sleep; urinalysis

DESCRIPTION (provided by applicant): Difficulty initiating/maintaining sleep afflicts up to 30% of the population, yet the neurochemical processes associated with sleep and sleep disturbances have not been clearly identified. A better understanding of EEG slow-wave activity and its role in recovery from sleep loss could be invaluable in elucidating the homeostatic sleep mechanism and shedding light on how to treat disturbed sleep. Further, sleep disturbances contribute to relapse to drug use and such efforts might help address this serious public health problem. The purpose of the study is to identify neurochemical markers of sleep mechanism in an intact and an impaired system, by evaluating changes in brain chemistry produced by disrupted sleep. In response to RFA-HL-01-009, "Interrelationship between sleep and heart, lung, and blood diseases" we propose two experiments. In the first, polysomnography (PSG) and phosphorous magnetic resonance spectroscopic imaging (31P MRSI) will be collected at baseline, after sleep deprivation, and after recovery sleep in controls and in methadone-maintained subjects. Measures will be repeated at 1 and 3 months to determine if the effects persist. In the second experiment, PSG and 31P MRSI data will be collected from unmedicated cocaine-dependent and opiate-dependent subjects during acute withdrawal and at 1 and 3 months post withdrawal. As the abstinence profile for sleep disturbance differs in these groups (hypersomnia vs insomnia, respectively) this experiment will help delineate the conditions under which altered brain bioenergenics exist. 31P MRSI can be used to measure global and focal changes in high energy phosphate alpha-,gamma-,beta-NTP (ATP). Our pilot data showed significant increases in beta-NTP and decreases in phospholipid catabolite production after recovery following sleep deprivation in control subjects. 31P MRS changes have been observed in chronic opiate-dependent individuals at baseline, but have not been evaluated during sleep. Chronic sleep disturbances have been reported in opiate abusers and methadone-maintained patients and the homeostatic sleep mechanisms may be impaired in chronic opiate abuse. We hypothesize that methadone-maintained subjects will have decreased beta-NTP and will exhibit smaller slow wave sleep rebound and a more modest or no increase in beta-NTP after recovery. Further, the neurochemical response to sleep deprivation in these subjects will approach that of controls over time b-NTP will increase during cocaine withdrawal and decrease during opiate withdrawal, reflecting their differential effects on sleep during this time. Collectively, these studies may identify neurochemical markers for the recovery function of sleep, thus enhancing our understanding pf basic sleep mechanisms and potentially leading to new and improved treatments for sleep disturbances in both the substance-abusing and general population.

描述（由申请人提供）：