"Uncoupling sleep deprivation-associated stressors from sleep loss in rodents"

“将啮齿动物睡眠不足与睡眠不足相关的压力源分开”

• 批准号: 8822760
• 负责人: Christopher John Davis
• 金额: $ 22万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8822760
• 关键词: Address; Affect; Animal Experimentation; Animal Model; Animals; Attention; Attenuated; Aversive Stimulus; Behavior; Biological Assay; Biological Markers; Brain; Brain Chemistry; Cognitive; Corticosterone; Corticotropin; Data; Destinations; Disadvantaged; Electroencephalography; Endocrine; Environment; Esthesia; Exhibits; Floor; Food deprivation (experimental); Future; Goals; Health; Hormones; Human; Human Characteristics; Hypothalamic structure; Impairment; Laboratories; Laboratory Study; Lateral; Lead; Learning; Locomotion; Measures; Methods; Modeling; Molecular Genetics; Outcome; Performance; Pharmaceutical Preparations; Plasma; Polysomnography; Process; Productivity; Prolactin; Protocols documentation; Public Health; Rat-1; Rattus; Research; Rewards; Rodent; Rodent Model; Safety; Self Stimulation; Self-Administered; Signal Transduction; Sleep; Sleep Deprivation; Stress; System; Task Performances; Techniques; Testing; Time; Training; Variant; Volition; Water; aversive conditioning; base; body position; hedonic; improved; in vivo; innovation; novel; public health relevance; research study; response; social; sound; stressor; vibration; vigilance

DESCRIPTION (provided by applicant): Many conclusions about brain sleep mechanisms are derived from animal sleep deprivation (SD) experiments. However, SD in animals is induced by uncontrollable (from the animal's perspective) aversive stimuli used in animal SD studies. In contrast, sleep loss in human experiments is voluntary. The overall goal of this project is to use intracranial self-stimulation (ICSS) as a rewarding, self-chosen method for rodent SD in order to un- couple the effects of the uncontrollable aversive components inherent in current animal SD protocols from the effects of sleep loss per se. We will compare gentle handling SD (GH-SD) vs. ICSS-SD vs. imposed brain stimulation (NCS-SD) in rats using polysomnography, plasma levels of ACTH, corticosterone, and prolactin, and performance on a sustained attention task. Thus, we will isolate the contributions of volition and aversiveness in SD-methods on each measure. The objectives of Aim 1 are to compare rat EEG and endocrine responses in GH-SD, NCS-SD and ICSS-SD. Pilot data show that ICSS is an effective technique for SD. We test the hypotheses that; 1) compared to GH-SD, ICSS-SD and NCS-SD rats will show similar sleep rebound, and 2) plasma expression of stress biomarkers are elevated after GH-SD compared to NCS-SD and ICSS-SD. Our recent data indicate that post-GH-SD performance on the rat psychomotor vigilance task (rPVT) shows important discrepancies with human PVT data. We developed a new rodent attention task, the nRAT. The objectives of Aim 2 are to: 1) contrast nRAT performance after each SD-type; and 2) compare post-SD changes in performance to those from SD human PVT experiments. We test the hypothesis that compared to the other SD-types, ICSS-SD will result in performance deficits in the nRAT that are more representative of performance occurring after SD in the human PVT. The proposed experiments will distinguish between uncontrollable aversive stimuli-induced vs. sleep loss-induced EEG, endocrine and cognitive responses. This proposal is innovative because we: a) compare responses induced by both ICSS and GH-SD methods of SD, b) develop a new self-imposed animal method to induce sleep loss devoid of forced and aversive SD techniques, c) vary SD-types in the nRAT and compare results with human PVT; and d) validate the nRAT as a model of post-SD time-on-task decrements in humans. Anticipated results will provide a new rewarding self-administered SD method and a new cognitive rodent task for use in animal brain mechanism studies -- a long term goal of this project.

描述（由申请人提供）：许多关于大脑睡眠机制的结论来自动物睡眠剥夺（SD）实验。然而，动物SD是由动物SD研究中使用的不可控（从动物的角度来看）厌恶刺激引起的。相比之下，人类实验中的睡眠损失是自愿的。本项目的总体目标是使用颅内自我刺激（ICSS）作为啮齿动物SD的奖励性自选方法，以将当前动物SD方案中固有的不可控厌恶成分的影响与睡眠丧失本身的影响分离。我们将使用多导睡眠图、ACTH、皮质酮和催乳素的血浆水平以及持续注意力任务的表现来比较大鼠中温和处理SD（GH-SD）与ICSS-SD与施加脑刺激（NCS-SD）。因此，我们将在每个测量上分离SD方法中的意志和厌恶的贡献。目的1的目的是比较GH-SD、NCS-SD和ICSS-SD中大鼠EEG和内分泌反应。中试数据表明ICSS是一种有效的SD技术。我们测试的假设，1）与GH-SD相比，ICSS-SD和NCS-SD大鼠将显示类似的睡眠反弹，以及2）与NCS-SD和ICSS-SD相比，GH-SD后应激生物标志物的血浆表达升高。我们最近的数据表明，后生长激素-SD性能的大鼠精神警觉任务（rPVT）显示与人类PVT数据的重要差异。我们开发了一种新的啮齿动物注意力任务，nRAT。目的2的目的是：1）对比每种SD类型后的nRAT性能; 2）将SD后的性能变化与SD人PVT实验的性能变化进行比较。我们测试的假设相比，其他SD类型，ICSS-SD将导致性能缺陷的nRAT，更有代表性的性能发生后，SD在人类PVT。拟议的实验将区分不可控的厌恶刺激与睡眠丧失诱导的EEG，内分泌和认知反应。该提议具有创新性，因为我们：a）比较了由SD的ICSS和GH-SD方法诱导的反应，B）开发了一种新的自我施加的动物方法来诱导睡眠丧失，而没有强迫和厌恶的SD技术，c）改变nRAT中的SD类型并将结果与人类PVT进行比较;以及d）验证了nRAT作为人类SD后任务时间减少的模型。预期的结果将提供一个新的奖励自我管理SD方法和一个新的认知啮齿动物的任务用于动物脑机制的研究-本项目的长期目标。