Effects of adolescent alcohol exposure on sleep and arousal in adulthood

描述（由申请人提供）：流行病学数据表明，过量饮酒在青少年中普遍存在，可能会产生持久的神经行为后果，包括增加形成酒精依赖的风险。据报道，睡眠困难在人类青少年中也很常见，并且睡眠不足已被证明与负面结果相关。我们实验室对大鼠的研究表明，青少年通过蒸气接触乙醇会导致睡眠和觉醒的变化，焦虑和情感行为以及皮质、海马和基底前脑神经生理功能的损害，直至成年。我们还表明，利用青少年时期在跑道上饮用乙醇的食欲体验的模型会导致成​​年期饮酒增加。本申请中的研究建议进一步开发一种结合这两种青少年酒精暴露方法的新模型。在组合模型中，老鼠被开始在跑道上有限地饮酒，随后在青春期期间间歇性接触酒精蒸气。该模型称为 ADORE（奔跑中饮酒/乙醇蒸气）。使用 ADORE 模型治疗后，我们将重点关注的成年期结果变量是神经行为（戒断、情感状态、饮酒）以及神经生理学测量（例如脑电图、事件相关电位 (ERP)、前脉冲抑制 (PPl)、睡眠），这些测量可转化为人类酒精滥用者的研究。我们还假设乙醇可能通过诱导基底前脑和脑桥胆碱能系统以及额叶皮层、下丘脑和杏仁核中的 NPY/CRF 系统的变化，对青少年产生一些影响。因此，我们假设这些神经通路的破坏会导致睡眠和觉醒的破坏，并促进对酒精和过量饮酒的耐受性的变化。这笔赠款中概述的研究将建立一个新模型，通过该模型，可以使用可转化为人类状况的措施来阐明青少年酒精暴露有害影响的机制。 公共健康相关性：该项目测试了这样的假设：在大鼠中，青春期接触酒精会导致睡眠和觉醒的长期变化、焦虑和情感行为以及皮质、海马和基础前脑功能的损害。这将为未来的实验铺平道路，以研究成年人大脑活动改变与已知在青春期接触酒精的成年人中酒精滥用增加之间的功能联系。

DESCRIPTION (provided by applicant): Epidemiological data indicate that excessive alcohol consumption is prevalent among adolescents and may have lasting neurobehavioral consequences including increased risk for the development of alcohol dependence. Sleep difficulties have also been reported to be common in human adolescents and inadequate sleep has been shown to be associated with negative outcomes. Studies from our laboratory, in rats, demonstrate that adolescent ethanol exposure via vapor can produce changes in sleep and arousal, impairments in anxiety and affective behavior as well as cortical, hippocampal, and basal forebrain neurophysiological function, well into adulthood. We have also shown that a model that employs the appetitive experience of drinking of ethanol in a runway during the adolescent period results in enhanced drinking during adulthood. Studies in this application propose to further develop a novel model that combines these two methods of adolescent alcohol exposure. In the combined model, rats are initiated to limited access alcohol drinking in a runway and are subsequently exposed to intermittent alcohol vapor during the adolescent period. The model is called ADORE (Alcohol Drinking On the Run/Ethanol vapor). The outcome variables in adulthood that we will focus on after treatment with the ADORE model are neurobehavioral (withdrawal, affective state, drinking) as well as neurophysiological measures (e.g. EEG, Event-related potentials (ERPs), Prepulse Inhibition (PPl), Sleep) that are translatable to studies in human alcohol abusers. It is also our hypothesis that ethanol may exert some of these effects on the adolescent, by inducing changes in basal forebrain and pontine cholinergic systems, as well as NPY/CRF systems in frontal cortex, hypothalamus, and amygdala. Thus, we postulate that a disruption in these neural pathways lead to disruptions in sleep and arousal and facilitates changes in tolerance to alcohol and excessive drinking. The studies outlined in this grant will establish a new model whereby the mechanisms underlying the deleterious effects of adolescent alcohol exposure can be elucidated in the adult using measures that are translatable to the human condition. PUBLIC HEALTH RELEVANCE: This project tests the hypothesis that in the rat, exposure to alcohol during adolescence induces long-term changes in sleep and arousal, impairments in anxiety and affective behavior, as well as cortical, hippocampal, and basal forebrain functioning. This will pave the way for future experiments that investigate functional links between this adult altered brain activity and the increased alcohol abuse known to take place in adults exposed to alcohol during adolescence