7/8 NADIA UO1 Adolescent Alcohol and Neurocircuitry Mediating Ethanol Reinforcement

7/8 NADIA UO1 青少年酒精和神经回路介导的乙醇强化

• 批准号: 9762557
• 负责人: ZACHARY Aaron RODD
• 金额: $ 31.59万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9762557
• 关键词: Adolescence; Adolescent; Adult; Alcohol consumption; Alcoholism; Alcohols; American; Amygdaloid structure; Animal Model; Anti-Anxiety Agents; Anxiety; Brain; Breeding; Cell Nucleus; Child; Choline O-Acetyltransferase; Chronic; Collaborations; Complex; Consumption; DNA Methylation; Data; Decision Making; Dendritic Spines; Dopamine; Drug Addiction; Epigenetic Process; Ethanol; Family history of; Genes; Genetic Predisposition to Disease; Goals; Grant; HDAC2 gene; Histone Acetylation; Histone Deacetylase; Histone Deacetylase Inhibitor; Impulsivity; Mediating; Microinjections; Morphology; Motivation; Neuroimmune; Neurotransmitters; Nucleus Accumbens; Pathway interactions; Pharmacology; Property; Psychological reinforcement; Rattus; Reporting; Research; Rewards; Self Administration; Site; Structure; Sucrose; System; Testing; Time; TimeLine; Ventral Tegmental Area; Wistar Rats; Withdrawal; adolescent alcohol exposure; adolescent alcohol risk; alcohol measurement; alcohol preferring rats; alcohol reinforcement; design; discount; discounting; drug reward; gamma-Aminobutyric Acid; high school; inhibitor/antagonist; neuroadaptation; neurochemistry; periadolescent; preference; promoter; public health relevance; reinforcer; response; underage drinking

 DESCRIPTION (provided by applicant): The vast majority of American children begin consuming alcohol prior to high school graduation and episodes of heavy ethanol consumption increase over time (Johnson et al., 1999, 2009). A family history of alcoholism increases the risk that adolescent alcohol consumption is associated with adult alcoholism (Agrawal et al., 2009). Periadolescent ethanol consumption by alcohol-preferring (P) rats increases the reinforcing properties of EtOH in the posterior ventral tegmental area (pVTA) during adulthood (Toalston et al., 2014). NADIA- generated research has indicated that adolescent intermittent ethanol (AIE) exposure results in persistent alterations in neuroimmune factors, choline acetyltransferase (ChAT), increased anxiety, and changes in histone acetylation altering neurocircuitry (Vetreno et al., 2014; Sakharkar et al., 2014). As a new component of the NADIA Consortium, the long-range objectives of this study are to determine the effects of AIE on the motivational, reinforcing and anxiolytic properties of EtOH during adulthood within the pVTA and central nucleus of the amygdala (CeA). The impact of a genetic predisposition to high alcohol consumption on the effects of AIE will be determined by making assessments in P rats. The overall hypothesis is that AIE results in lasting neurotransmitter system, epigenetic, and structural alterations in regions critical for motivation, reinforcement, and anxiety. The goals of the application are 1) to assess alterations in the reinforcing properties of EtOH in the pVTA and CeA produced by AIE, 2) to evaluate the neurochemical response to EtOH in the pVTA induced by AIE, 3) to determine if histone deacetylase (HDAC) inhibitor treatment reverses the alterations produced by AIE, 4) to determine the impact of AIE on probabilistic decision-making. In Aim 1, we will test the hypothesis that AIE induced neuroadaptations within the pVTA alter EtOH reinforcement and the neurochemical response to EtOH during adulthood. In Aim 2, we will test the hypothesis that AIE induced neuroadaptations within the pVTA can be reversed by site specific administration of HDAC inhibitor during adulthood. In Aim 3, we will test the hypothesis that AIE induced neuroadaptations within the CeA alter the reinforcing and anxiolytic properties of EtOH during adulthood. In Aim 4, we will test the hypothesis that AIE has altered the probabilistic decision-making (an animal model of impulsivity) during adulthood. This is a highly significant project that will attempt to elucidate the complex factors that underlie the effects of AIE on adult EtOH usage.

 描述（通过应用程序提供）：绝大多数美国儿童在高中毕业之前开始饮酒，并且随着时间的推移，大量乙醇消费量会增加（Johnson等，1999，2009）。酒精中毒的家族史增加了青少年饮酒与成人酒精中毒有关的风险（Agrawal等，2009）。在成年期，饮酒（P）大鼠饮酒（P）大鼠的乙醇消耗增加了EtOH的增强特性（PVTA）（Toalston等，2014）。纳迪亚（Nadia）产生的研究表明，青春期间歇性乙醇（AIE）暴露会导致神经免疫性因子，胆碱乙酰基转移酶（CHAT），焦虑症和组蛋白乙酰化的变化改变神经记录的变化（Vetreno等人（Vetreno等）。作为纳迪亚财团的新组成部分，本研究的远程目标是确定AIE对动机，增强的影响 ETOH在PVTA和杏仁核中央核的成年期间的抗焦虑特性（CEA）。遗传倾向对高酒精消耗对AIE影响的影响将通过对P大鼠进行评估来确定。总体假设是，AIE导致了持久的神经递质系统，表观遗传和结构变化，对动机，增强和动画至关重要。应用程序的目标是1） 评估AIE产生的PVTA和CEA中ETOH的增强特性的变化，2）评估AIE诱导的PVTA中对ETOH的神经化学反应，3），以确定组蛋白脱乙酰酶（HDAC）抑制剂治疗是否会导致AIE产生的变化，以确定AIE的影响，以确定AIE的影响。在AIM 1中，我们将检验以下假设：AIE在PVTA中诱导的神经适应性改变ETOH增强和成年期间对EtOH的神经化学反应。在AIM 2中，我们将检验以下假设：AIE诱导的PVTA内神经加热可以通过成年期间HDAC抑制剂的特定施用来逆转。在AIM 3中，我们将检验以下假设：AIE在CEA内诱导的神经适应改变了成年期间EtOH的增强和抗焦虑特性。在AIM 4中，我们将检验以下假设：AIE在成年期改变了概率决策（一种冲动性的动物模型）。这是一个非常重要的项目 将尝试阐明AIE对成人ETOH使用影响的复杂因素。