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，过度饮酒在青少年中很普遍，并可能产生持久的神经行为后果，包括增加酒精依赖的风险。据报道，睡眠困难在青少年中也很常见，睡眠不足已被证明与负面结果有关。我们实验室对大鼠的研究表明，青少年通过蒸汽接触乙醇会导致睡眠和觉醒的改变，焦虑和情感行为的损害，以及皮层、海马和基底前脑的神经生理功能的损害，一直持续到成年。我们还表明，一个模型采用了青少年时期在跑道上饮用乙醇的食欲体验，结果导致成年期饮酒增加。本应用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。在联合模型中，大鼠开始在跑道上有限地饮酒，随后在青春期暴露于间歇性酒精蒸气中。这种模式被称为ADORE（边跑边喝酒/酒精蒸气）。我们将重点关注的成年后的结果变量是神经行为（戒断，情感状态，饮酒）以及神经生理测量（如脑电图，事件相关电位（ERPs），脉冲前抑制（PPl），睡眠），这些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，对青少年产生这些影响。因此，我们假设这些神经通路的中断会导致睡眠和觉醒的中断，并促进对酒精和过度饮酒的耐受性的变化。这项拨款中概述的研究将建立一个新的模型，据此，青少年酒精接触有害影响的潜在机制可以在成人中通过可转化为人类状况的措施加以阐明。

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.