"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）：关于脑睡眠机制的许多结论来自动物睡眠剥夺（SD）实验。然而，动物中使用的（从动物的角度来看）在动物SD研究中使用的厌恶刺激引起了动物中的SD。相反，人类实验中的睡眠损失是自愿的。该项目的总体目标是将颅内自我刺激（ICS）用作啮齿动物SD的有意义的，自我选择的方法，以使当前动物SD方案中无法控制的厌恶成分的影响从睡眠损失的效果中造成的影响。我们将使用多聚会摄影，ACTH的血浆水平，皮质酮和催乳素的水平在大鼠中比较柔和的处理SD（GH-SD）与ICSS-SD与施加的大脑刺激（NCS-SD），以及在持续注意任务中的性能。因此，我们将隔离每个度量中SD方法中的意志和厌恶性的贡献。 AIM 1的目标是比较GH-SD，NCS-SD和ICSS-SD中的大鼠EEG和内分泌反应。试点数据显示，ICS是SD的有效技术。我们测试了假设； 1）与GH-SD相比，ICSS-SD和NCS-SD大鼠将显示出相似的睡眠反弹，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，GH-SD后关于大鼠心理运动警惕任务（RPVT）的表现显示了人类PVT数据的重要差异。我们制定了一项新的啮齿动物注意任务，即NRAT。 AIM 2的目标是：1）每种SD型后对比NRAT性能； 2）比较SD人类PVT实验的SD性能变化。我们检验了与其他SD类型相比的假设，ICSS-SD将导致NRAT的性能缺陷，这些缺陷更代表了人类PVT中SD后发生的性能。所提出的实验将区分不抗厌恶性刺激诱导的与睡眠损失诱导的脑电图，内分泌和认知反应。该提议具有创新性，因为我们：a）比较SD的ICS和GH-SD方法诱导的反应，b）开发一种新的自我强制动物方法，以诱导没有强制性和厌恶性SD技术的睡眠损失，c）在NRAT中不同的SD型，并将其与人类PVT进行比较； d）将NRAT验证为人类中SD后时间降低的模型。预期的结果将提供一种新的有益的自我管理SD方法，并提供一项新的认知啮齿动物任务，以用于动物脑机理研究 - 该项目的长期目标。