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很普遍，可能会产生持久的神经行为后果，包括增加发展成酒精依赖的风险。据报道，睡眠困难在人类青少年中也很常见，睡眠不足被证明与负面结果有关。我们实验室在大鼠身上进行的研究表明，青春期通过蒸气接触酒精可以导致睡眠和唤醒的变化，焦虑和情感行为的损害，以及皮质、海马体和基底前脑的神经生理功能，一直持续到成年。我们还表明，在青春期使用在跑道上喝乙醇的胃口体验的模型会导致成年后饮酒量增加。这项应用的研究建议进一步开发一种新的模式，将这两种青少年酒精暴露的方法结合起来。在联合模型中，大鼠开始在跑道上有限地饮酒，然后在青春期间歇性接触酒精蒸气。这一模型被称为ADORE(奔跑中饮酒/乙醇蒸气)。成年后，我们将关注ADORE模型治疗后的结果变量是神经行为(戒断、情感状态、饮酒)以及神经生理指标(例如脑电、事件相关电位(ERPs)、脉冲前抑制(PPL)、睡眠)，这些指标可以转化为对人类酒精滥用者的研究。这也是我们的假设，乙醇可能通过诱导基底前脑和桥脑胆碱能系统以及额叶皮质、下丘脑和杏仁核的NPY/CRF系统的变化，对青少年产生其中的一些影响。因此，我们推测，这些神经通路的中断会导致睡眠和觉醒的中断，并有助于改变对酒精和过度饮酒的耐受性。这笔赠款中概述的研究将建立一个新的模型，通过该模型，可以使用可根据人类情况翻译的措施，在成人中阐明青少年酒精暴露有害影响的潜在机制。 与公共健康相关：该项目测试了一种假设，即在青春期接触酒精会导致大鼠睡眠和唤醒的长期变化，焦虑和情感行为的损害，以及皮质、海马体和基底前脑功能的变化。这将为未来的实验铺平道路，这些实验将研究这种成年人大脑活动的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