Physiological Characterization of REM Sleep in Chronic Alcohol-Exposed Rats

慢性酒精暴露大鼠快速眼动睡眠的生理特征

• 批准号: 9042194
• 负责人: Stephanie Perreau-Lenz
• 金额: $ 9.99万
• 依托单位: SRI INTERNATIONAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9042194
• 关键词: Abstinence; Acute; Addictive Behavior; Address; Affect; Alcohol abuse; Alcohol consumption; Alcohol withdrawal syndrome; Alcoholism; Alcohols; Aminobutyric Acids; Animal Model; Animals; Arousal; Behavior; Behavioral; Biological Markers; Brain; Brain Stem; Brain region; Cell Nucleus; Characteristics; Chronic; Circadian Rhythms; Clinical; Clinical Research; Complex; Conflict (Psychology); Consumption; Disease; Electroencephalogram; Electrophysiology (science); Ethanol; Exposure to; Family Felidae; GABA Agents; GABA Receptor; Generations; Glutamates; Goals; Health; Heart; Human; In Vitro; Intake; Investigation; Knowledge; Laboratory Rat; Lead; Length; Link; Liver; Long-Term Effects; Maintenance; Measurement; Measures; Mediating; Memory impairment; Mental Depression; Methods; Microdialysis; Modeling; Morbidity - disease rate; Morphology; N-Methylaspartate; Neurobiology; Neurons; Neurotransmitters; Organ; Outcome; Parasomnias; Pharmaceutical Preparations; Physiological; Pontine structure; Prosencephalon; Quality of life; REM Sleep; Rat Strains; Rattus; Regulation; Relapse; Research; Restless Legs Syndrome; Reticular Formation; Rodent; Rodent Model; Role; Sampling; Site; Sleep; Sleep Disorders; Sleep Wake Cycle; Sleep disturbances; Sleeplessness; Slow-Wave Sleep; Study models; Testing; Thalamic structure; Therapeutic Intervention; Time; Wakefulness; Water; Withdrawal; Woman; addiction; alcohol effect; alcohol exposure; alcohol relapse; base; brain behavior; cellular targeting; chronic alcohol ingestion; drinking; gamma-Aminobutyric Acid; in vivo; insight; limb movement; men; mortality; neurochemistry; neurotransmission; novel; pharmacokinetic model; prevent; problem drinker; rapid eye movement; research study; sleep abnormalities; sleep regulation; targeted treatment; therapy design; tool; vigilance

DESCRIPTION (provided by applicant): Alcoholism leads to detrimental alterations to vital organs, including the liver, heart, and brain. Chronic alcoholics show significant deficits in brai morphology accompanied by behavioral alterations leading to addiction, depression, memory deficits, and sleep disturbances. Well-documented sleep problems in alcoholics include, disrupted circadian and ultradian rhythms, insomnia, and parasomnias. Rapid eye movement (REM) sleep is especially vulnerable to the effects of alcohol, and altered REM sleep parameters have been considered significant predictors of relapse in abstinent alcoholics. Additional evidence suggests that the long- term abuse of alcohol affects REM sleep long after alcoholics remain abstinent. Given that alcohol alters inhibitory (GABA) mechanisms and also mediates REM sleep regulation; this neurotransmitter may lead to a crucial link between alcoholism's impact on the neurochemical disruption of vigilance states and REM sleep regulation in particular. The goal of our proposed study is to examine the effects of chronic alcohol consumption on wake and sleep measures in the rat, and additionally address whether GABA mechanisms mediating REM sleep are permanently disrupted by alcohol abuse. Although there are several well- characterized rat models that have provided novel insights into alcoholism's impact on the brain and addictive behavior, research performed on sleep-wake in rodents has provided variable results dependent on animal species, sleep parameters studied, method of ethanol administration, and none have characterized alcohol's impact on the neuronal mechanisms of REM sleep behavior. We hypothesize that chronic ethanol (EtOH) consumption will lead to alterations in spontaneous REM sleep behavior and consequent changes in the REM sleep-regulated brainstem and thalamus of the rat. We will assess the behavioral consequences of long-term EtOH exposure on the electrophysiological characteristics of wake, slow wave sleep, REM sleep, and EEG spectral measures in the standard laboratory rat. Additionally, we will use in vivo microdialysis to assess brainstem and thalamic fluctuations in GABA across the sleep-wake cycle in naive rats, drinking rats and rats that have undergone EtOH withdrawal. The results of these studies will provide insights into the effects of alcohol abuse on sleep-wakefulness and serve as a model for studies evaluating withdrawal and relapse.

描述（由申请人提供）：酒精中毒会导致对重要器官（包括肝脏，心脏和大脑）的有害改变。慢性酗酒者在Brai形态上表现出严重的缺陷，并伴有行为改变，导致成瘾，抑郁，记忆缺陷和睡眠障碍。酗酒者中有充分记录的睡眠问题包括昼夜节律和超级节奏，失眠和旁白。快速眼动（REM）睡眠尤其容易受到酒精的影响，而改变的REM睡眠参数已被认为是戒酒中复发的重要预测指标。其他证据表明，在戒酒后很长一段时间内，长期滥用酒精会影响REM睡眠。鉴于酒精会改变抑制性（GABA）机制，并介导REM睡眠调节；这种神经递质可能导致酒精中毒对警惕态的神经化学破坏的影响与尤其是REM睡眠调节之间的关键联系。我们拟议的研究的目的是检查慢性酒精消耗对大鼠唤醒和睡眠度量的影响，并介绍介导REM睡眠的GABA机制是否会因酒精滥用而永久破坏。尽管有几种良好的大鼠模型为酒精中毒对大脑的影响和上瘾行为提供了新的见解，但对啮齿动物睡眠效果进行的研究提供了可变结果，取决于动物物种，研究的睡眠参数，乙醇的施用方法，没有一个对酒精对神经性睡眠机制的影响。我们假设慢性乙醇（ETOH）的消费将导致自发性REM睡眠行为的改变，并导致REM睡眠调节的脑干和大鼠丘脑的变化。我们将评估标准实验室大鼠中长期ETOH暴露对唤醒，慢波睡眠，REM睡眠和EEG光谱测量的电生理特征的行为后果。此外，我们将使用体内微透析来评估幼稚大鼠睡眠效果周期中GABA的脑干和丘脑的波动，喝了戒断ETOH的大鼠，饮用大鼠和大鼠。这些研究的结果将提供有关酗酒对睡眠消耗性的影响的见解，并作为评估戒断和复发的研究的模型。