Rehabilitation of Stress-Induced Insomnia

压力引起的失眠的康复

• 批准号: 9062877
• 负责人: PINGFU FENG
• 金额: --
• 依托单位: LOUIS STOKES CLEVELAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9062877
• 关键词: Acute; Affect; Agonist; Animal Model; Antidepressive Agents; Brain; Chronic; Chronic Insomnia; Clinical; Collection; Corticotropin-Releasing Hormone; Data; Disease; Eszopiclone; Evaluation; Extracellular Fluid; General Population; Goals; Hypothalamic structure; Infusion procedures; Intervention; Longitudinal Studies; Maternal Deprivation; Medical; Mental Depression; Microdialysis; Mission; Modeling; Molecular; Neonatal; Neural Pathways; Neurobiology; Pathology; Patient Care; Pharmaceutical Preparations; Polysomnography; Post-Traumatic Stress Disorders; Qualifying; Radioimmunoassay; Rattus; Regulation; Rehabilitation therapy; Risk; Severities; Sleep; Sleep Disorders; Sleeplessness; Stress; Techniques; Toxic effect; Trazodone; United States; Work; abstracting; clinically significant; hypnotic; improved; insight; novel marker; psychological distress; research study; sleep abnormalities; sleep regulation; treatment duration; treatment effect; treatment strategy

Feng, Rehabilitation of Stress-Induced Insomnia 1 Abstract The goal of this project is to evaluate and compare how the acute treatment with hypnotics that have different mechanisms would improve sleep and suppress the brain levels of corticotropin-releasing hormone (CRH) and the orexins which are involved in the neurobiological pathology for insomnia, and to evaluate whether a long term treatment with several different hypnotics would eventually rehabilitate both the sleep disorder and the neurobiological abnormalities in a chronic rat model of insomnia. We propose two objectives to separately study how the drugs eszopiclone (Lunesta, a non-benzodiazepine GABAergic agonist) and trazodone (a commonly prescribed antidepressant used for insomnia) affect sleep in acute (two days) treatment and chronic treatment (two weeks), and whether these drugs suppress hypothalamic CRH and orexins directly by acute brain infusion and indirectly by chronic systemic treatment. All experiment will be conducted in a rat model of chronic insomnia induced by neonatal maternal deprivation in comparison to that in control subjects. Four major techniques will be applied. This includes (1) to us a rat model of insomnia induced by the neonatal maternal deprivation, (2) polysomnographic recording, a classic technique for sleep evaluation, (3) microdialysis for extracellular fluid collection and (4) use radioimmunoassay to quantify the levels of CRH and orexins. We have sufficient preliminary data in support of the feasibility of using these techniques. Clinical significance： We propose two objectives for this project: to answer the key questions of whether short term or long term treatment with different types of hypnotics would recover the abnormalities of sleep and the neurobiological markers in the chronic model of insomnia. The successful completion of the project would allow us to outline the immediate and the chronic effects of treatment with eszopiclone and trazodone on sleep and brain CRH and the orexins, and to correlate the immediate effect of these drugs on hypothalamic CRH and the orexins with the long term efficacy of insomnia treatment. These results would be able to help in improving the current understanding in the treatment strategy for chronic insomnia. Relevance of the Proposed Work to the VA Patient Care Mission Insomnia is a common disorder in the general population in the United States and chronic insomnia is present in 70% of those with PTSD. It leads to impaired next-day functioning and psychological distress, and is a predictor of later increased depression risk. Successful completion of the study of orexinergic involvement in the pathological regulation of hyperarousal in insomnia will provide important new insights into the neurobiological regulation of insomnia, and may provide new directions for its treatment.

Feng，Rehabilitation of Stress-Induced Inflammation 1 摘要 本项目的目的是评估和比较催眠药的急性治疗， 不同的机制会改善睡眠，抑制大脑中促肾上腺皮质激素释放激素的水平， (CRH)以及参与失眠神经生物学病理学的食欲素，并评估是否 用几种不同的催眠药进行长期治疗， 慢性失眠大鼠模型的神经生物学异常。我们提出两个目标，分别 研究药物右佐匹克隆（Lunesta，一种非苯二氮卓类GABA能激动剂）和曲唑酮（一种 通常用于失眠的处方抗抑郁药）在急性（两天）治疗和慢性治疗中影响睡眠 治疗（两周），以及这些药物是否通过急性脑损伤直接抑制下丘脑CRH和食欲素 输注和通过慢性全身治疗间接进行。所有实验将在慢性炎症大鼠模型中进行。 与对照组相比，新生儿母亲剥夺引起的失眠。四大 技术将被应用。这包括（1）给我们一个由新生儿母亲诱导的大鼠失眠模型 剥夺，（2）多导睡眠图记录，睡眠评估的经典技术，（3）微透析， 细胞外液收集和（4）使用放射免疫测定来定量CRH和食欲素的水平。我们有 充分的初步数据，以支持使用这些技术的可行性。 临床意义： 我们为这个项目提出了两个目标：回答是短期还是长期的关键问题 用不同类型的催眠药治疗可以恢复睡眠和神经生物学的异常。 慢性失眠模型中的标志物。该项目的成功完成将使我们能够概述 右佐匹克隆和曲唑酮治疗对睡眠和脑CRH的即刻和长期影响， 食欲素，并将这些药物对下丘脑CRH和食欲素的直接作用与长期作用联系起来。 长期治疗失眠疗效显著。这些结果将有助于提高目前的认识 慢性失眠症的治疗策略。 拟定工作与VA患者护理使命的相关性 失眠是美国普通人群中的常见疾病， 70%的PTSD患者它会导致第二天的功能受损和心理困扰， 抑郁症风险的增加。成功完成食欲素能参与 失眠症中过度觉醒的病理调节将为神经生物学提供重要的新见解， 调节失眠，并可能为其治疗提供新的方向。