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: 8531065
• 负责人: LINDA PATIA SPEAR
• 金额: $ 31.33万
• 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/8531065
• 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）：青春期是对压力敏感的大脑区域进行巨大转变的时期，在处理奖励和社会/情感刺激的处理以及对这些地区进行监管控制的地区。鉴于，当对这些物质敏感的系统发生变化时，最有可能发生持久的物质作用，我们假设青少年间歇性乙醇（AIE）暴露会引起对社会行为以及乙醇的社会奖励和厌恶作用的持久影响，从而导致成人的社交疗法在成人的社会抗心性中导致成人持续的升高。的确，酒精的社会奖励影响对于在青春期开始使用酒精和社交焦虑症患者的大量饮酒至关重要，与非依赖，社交焦虑的人相比，社交焦虑的酗酒者表现出更大的社会障碍。拟议的研究将研究自愿和实验者管理的青少年间歇性酒精（AIE）对以后的社交焦虑和奖励的后果，酒精对这些对乙醇的持久扰动的疗效以及对乙醇的后来自愿摄入的影响，以及这些影响的神经/遗传适应性。使用NADIA提供的协同作用，拟议的研究将解决以下目的：（1）测试AIE是否会在成年期间在社交状况下增加基线焦虑行为水平，并加剧压力引起的社交焦虑，并确定急性乙醇的功效，以逆转这种社交焦虑； （2）确定AIE暴露是否破坏了社会刺激的有意义和/或享乐值，这些改变是否会因压力而进一步加剧，以及急性乙醇对逆转这些影响的功效； （3）评估AIE是否会增强成年后的乙醇饮酒，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后的社会环境进一步加剧； （4）通过测量响应社会刺激的伏隔核中的实时多巴胺释放，研究了对成​​年多巴胺传播的影响，并评估了关键边缘区域中与多巴胺相关的基因表达。 公共卫生相关性：拟议的调查对青少年酒精暴露对社交焦虑，酒精的抗焦虑特性以及神经/遗传适应不足的持久影响具有相当大的相关性，鉴于饮酒在启动社交焦虑症的人中，与社交焦虑症的人相处的重大饮酒中，社交奖励的重要性以及在社交障碍中的重大饮酒中的重要性，以及在社交中所看到的焦虑症中所看到的。