Collaboration on Alcohol Self-Administration in Adolescents and Young Adults

描述(由申请人提供)：这项国际合作U01计划在印第安纳大学医学院和德国德累斯顿工业大学的研究人员之间交流新的酒精管理技术，然后进行研究，提供新的知识，补充这两个机构正在进行的现有活动。由Co-Pis发明、开发和验证的计算机辅助乙醇自我给药(CASE)系统将在德国前瞻性地用于评估80名青少年的初始饮酒轨迹，这些青少年因有不同的家族酗酒风险史而被招募。在16岁和18岁进行饮酒自我管理的病例评估之前，将对样本进行酒精使用障碍症状和最近饮酒史的评估。饮酒轨迹的初始斜率将根据病例表现的变化计算，并测试与其他风险因素的关联。德累斯顿还将使用fMRI扫描过程中执行的停止信号任务，评估酒精对一半样本人群的额叶冲动测量的影响。通过印第安纳州开发的自动钳位系统，fMRI相机中每个受试者的大脑暴露在酒精中的时间进程将几乎相同。在印第安纳波利斯，其目的是评估CASE区分“喜欢”和“想要”酒精的能力，作为酒精自我给药行为的基础，为药物开发研究做准备。将比较两种案例范例；一种评估自我饮酒的享乐主义影响；另一种量化为更多酒精而工作的意愿。将采用交叉设计，样本人群为80名年轻成年饮酒者。将评估每个范例中的病例表现，以确定在启动间隔结束时对主观感知的不同敏感性，以及酒精依赖的风险因素，包括不同的家族酗酒史、个人近期饮酒史和酒精使用障碍症状清单。印第安纳州还将对德国和美国样本人群进行基因分型，并寻求酒精脱氢酶簇中的SNP单倍型与酒精代谢和其他风险因素之间的联系。 公共卫生相关性：这项最初的申请直接涉及PAR-08-004中重视的研究重点；药效学、酒精遗传学和表观遗传学、风险的生物标志物、暴露在青少年身上的影响，以阐明饮酒开始与酒精使用障碍的发展之间的关系。这种伙伴关系是真实的和平衡的，U01领导计划结合了NIAAA的协作资源。

DESCRIPTION (provided by applicant): This proposal for an International Collaborative U01 exchanges novel alcohol administration techniques between investigators at the Indiana University School of Medicine and the Technical University of Dresden, Germany, then undertakes research that contributes new knowledge complementing ongoing existing activities at both institutions. The Computer-Assisted Self-administration of Ethanol (CASE) system, invented, developed and validated by the Co-PIs, will be used prospectively in Germany to assess the initial drinking trajectories of 80 adolescents, recruited for a differential risk history of familial alcoholism. The sample will be assessed for symptoms of alcohol use disorders and recent drinking history prior to CASE assessments of alcohol self administration for enjoyment, conducted at ages 16 and 18. The initial slope of drinking trajectories will be computed from changes in CASE performance, and tested for association with the other risk factors. Dresden will also assess the effects alcohol on frontal lobe measures of impulsivity in half the sample population, using the Stop-Signal task performed during fMRI scanning. The time-course of brain exposure to alcohol in the fMRI camera will be nearly identical in every subject, accomplished by an autoclamping system, developed in Indiana. In Indianapolis, the aim is to assess the capacity of CASE to differentiate "liking" from "wanting" alcohol as bases for alcohol self-administration behavior in preparation for drug-development studies. Two CASE paradigms will be compared; one assessing the hedonic impact of alcohol self-administration; the other quantifying the willingness to work for more alcohol. A crossover design in a sample population of 80 young adult drinkers will be employed. CASE performance in each paradigm will be assessed for differential sensitivity to subjective perceptions at the end of a priming interval, and to risk factors for alcohol dependence that include differential history of familial alcoholism, personal recent drinking history, and an inventory of alcohol use disorder symptoms. Indiana will also genotype both German and American sample populations and seek associations between SNP haplotypes in the alcohol dehydrogenase cluster and alcohol metabolism and other risk factors. PUBLIC HEALTH RELEVANCE: This original application directly addresses research priorities valued in PAR-08-004; pharmacodynamics, alcohol genetics and epigenetics, biomarkers of risk, effects of exposure on the adolescent that elucidate the relationship between drinking onset, and the development of alcohol use disorders. The partnership is real and well balanced, and the U01 leadership plan incorporates the collaborative resources of NIAAA.