Impact of adolescent intermittent ethanol on adult social reward and anxiety

描述（由申请人提供）：青春期是压力敏感脑区发生重大转变的时期，这些脑区在奖励和社会/情感刺激的处理中发挥关键作用，并在对这些区域施加调节控制的区域中发挥关键作用。鉴于物质的持久影响最有可能发生时，系统敏感的这些物质正在发生变化的发展，我们假设，青少年间歇性乙醇（AIE）暴露将诱导持久的影响社会行为和社会奖励和厌恶的影响乙醇，导致持续升高成人摄入量部分由于酒精的社会抗焦虑特性。事实上，酒精的社会回报效应对于青少年开始饮酒以及社交焦虑个体升级为酗酒至关重要，社交焦虑的酗酒者比不依赖、社交焦虑的个体表现出更大程度的社交障碍。拟议的研究将调查自愿和实验者管理的青少年间歇性酒精（AIE）对后来的社会焦虑和奖励的后果，酒精对抗这些社会行为中的持久扰动的功效，以及对后来自愿摄入乙醇的影响，沿着这些影响背后的神经/遗传适应。利用NADIA提供的协同效应，拟议的研究将解决以下目标：（1）测试AIE是否增加成年后社交环境下焦虑样行为的基线水平，并加剧压力诱导的社交焦虑，并确定急性乙醇逆转这种社交焦虑的疗效;（2）确定AIE暴露是否破坏了社会刺激的奖励和/或享乐价值，这些改变是否会因压力而进一步加剧，以及急性乙醇逆转这些影响的功效;（3）评估AIE是否会增加成年期的乙醇饮用量并降低对乙醇厌恶性的敏感性，以及AIE的这些影响是否会因成年期的社会环境而进一步加剧;（4）通过测量响应于社会刺激的丘脑核中的实时多巴胺释放并评估关键边缘系统区域中多巴胺相关基因的表达来研究AIE对成年期多巴胺传递的影响。 公共卫生相关性：建议的调查青少年酒精暴露对社交焦虑的持久影响，酒精的抗焦虑特性，以及潜在的神经/遗传适应性具有相当大的相关性，因为酒精的社会奖励特性在社交焦虑的个体中开始使用和升级到大量饮酒的重要性，沿着在社交焦虑的酗酒者中看到的更大的社会损害。

DESCRIPTION (provided by applicant): Adolescence is a time of considerable transformation in stress-sensitive brain regions that play key roles in the processing of rewarding and social/emotional stimuli and in areas that exert regulatory control over these regions. Given that lasting effects of substances are most likely to occur when systems sensitive to those substances are changing developmentally, we hypothesize that adolescent intermittent ethanol (AIE) exposure will induce lasting effects on social behavior and on the social rewarding and aversive effects of ethanol, leading to persistent elevations in adult intake due in part to alcohol's social anxiolytic properties. Indeed, social rewarding effects of alcohol are critical for the initiation of alcohol use in adolescence and escalation to heavy drinking among individuals with social anxiety, with socially anxious alcoholics showing greater levels of social impairment than non-dependent, socially anxious individuals. The proposed studies will investigate the consequences of voluntary and experimenter-administered adolescent intermittent alcohol (AIE) on later social anxiety and reward, the efficacy of alcohol for countering these lasting perturbations in social behavior, and the impact on later voluntary intake of ethanol, along with neural/genetic adaptations underlying these effects. Using synergisms provided by the NADIA, the proposed research will address the following aims: (1) test whether AIE increases baseline levels of anxiety-like behavior under social circumstances in adulthood and exacerbates stress-induced social anxiety, and determine the efficacy of acute ethanol for reversing this social anxiety; (2) determine whether AIE exposure disrupts the rewarding and/or hedonic value of social stimuli, whether these alterations are further exacerbated by stress, and the efficacy of acute ethanol for reversing these effects; (3) assess whether AIE enhances ethanol drinking in adulthood and decreases sensitivity to the aversive properties of ethanol, and whether these effects of AIE are further exacerbated by social context in adulthood; (4) investigate AIE effects on dopamine transmission during adulthood by measuring real-time dopamine release in nucleus accumbens in response to social stimuli and assessing dopamine-related gene expression in key limbic regions. PUBLIC HEALTH RELEVANCE: The proposed investigations of lasting effects of adolescent alcohol exposure on social anxiety, alcohol's anxiolytic properties, and underiying neural/genetic adaptations are of considerable relevance, given the importance of alcohol's social rewarding properties in initiating use and escalating to heavy drinking among individuals with social anxiety, along with the greater social impairment seen in socially anxious alcoholics.