Impact of adolescent intermittent ethanol on adult social reward and anxiety

青少年间歇性饮酒对成人社交奖励和焦虑的影响

• 批准号: 8137371
• 负责人: LINDA PATIA SPEAR
• 金额: $ 34.42万
• 依托单位: STATE UNIVERSITY OF NY,BINGHAMTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-05 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8137371
• 关键词: Acute; Address; Adolescence; Adolescent; Adult; Alcohol consumption; Alcohols; Amygdaloid structure; Animals; Anti-Anxiety Agents; Anxiety; Area; Behavior; Brain; Brain region; Chronic; Chronic stress; Development; Dopamine; Ethanol; Exposure to; Gene Expression; Genetic; Heavy Drinking; Impairment; Individual; Intake; Interdisciplinary Study; Investigation; Measures; Microarray Analysis; Nucleus Accumbens; Play; Property; Proteins; Rattus; Research; Rewards; Scanning; Social Behavior; Social Conditions; Social Environment; Social Facilitation; Social Interaction; Social Values; Stimulus; Stress; System; Taste Perception; Testing; Time; Ultrasonics; Ventral Tegmental Area; adolescent alcohol exposure; age related; alcohol consequences; alcohol effect; alcohol exposure; alcohol sensitivity; alcohol use initiation; dopamine system; emotional stimulus; hedonic; indexing; preference; problem drinker; public health relevance; relating to nervous system; response; reward processing; social; synergism; transmission process; underage drinking; vocalization

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.

描述（由申请人提供）：青春期是压力敏感大脑区域发生重大转变的时期，这些区域在奖励和社会/情感刺激的处理以及对这些区域施加调节控制的区域中发挥着关键作用。鉴于当对这些物质敏感的系统发生发育变化时，物质的持久影响最有可能发生，我们假设青少年间歇性乙醇（AIE）暴露将对社会行为以及乙醇的社会奖赏和厌恶效应产生持久影响，导致成人摄入量持续增加，部分原因是酒精的社交抗焦虑特性。事实上，酒精的社会奖赏效应对于患有社交焦虑的个体在青春期开始饮酒以及升级为大量饮酒至关重要，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损害。拟议的研究将调查自愿和实验者管理的青少年间歇性饮酒（AIE）对以后的社交焦虑和奖励的影响，酒精对抗这些持久的社会行为扰动的功效，以及对以后自愿摄入乙醇的影响，以及这些影响背后有神经/遗传适应。利用 NADIA 提供的协同作用，拟议的研究将实现以下目标：（1）测试 AIE 是否会增加成年期社交环境下焦虑样行为的基线水平并加剧压力引起的社交焦虑，并确定急性乙醇的功效扭转这种社交焦虑； (2) 确定 AIE 暴露是否会破坏社会刺激的奖励和/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特性的敏感性，以及 AIE 的这些影响是否会因成年期的社会背景而进一步加剧； (4) 通过测量伏核响应社会刺激的实时多巴胺释放并评估关键边缘区域的多巴胺相关基因表达，研究 AIE 对成年期间多巴胺传递的影响。 公共健康相关性：考虑到酒精的社会回报特性对于青少年开始使用酒精并升级为大量饮酒的重要性，拟议的调查青少年酒精暴露对社交焦虑、酒精的抗焦虑特性和潜在的神经/遗传适应性的持久影响具有相当大的相关性。患有社交焦虑症的人，以及社交焦虑型酗酒者的社交障碍更大。