Collaboration on Alcohol Self-Administration in Adolescents and Young Adults

描述（由申请人提供）：本国际合作U01提案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，贡献新知识，补充两所机构正在进行的现有活动。计算机辅助酒精自我管理（CASE）系统，由co - pi发明、开发和验证，将在德国前瞻性地用于评估80名青少年的初始饮酒轨迹，这些青少年被招募用于家族酒精中毒的不同风险史。在对16岁和18岁的青少年进行酒精自我管理的个案评估之前，将对样本进行酒精使用障碍症状和近期饮酒史的评估。饮酒轨迹的初始斜率将根据CASE表现的变化来计算，并测试与其他风险因素的关联。德累斯顿还将利用功能磁共振成像扫描期间执行的停止信号任务，评估酒精对一半样本人群额叶冲动性测量的影响。在功能磁共振成像（fMRI）相机中，每个受试者的大脑暴露于酒精的时间过程几乎是相同的，这是由印第安纳州开发的自动夹紧系统完成的。在印第安纳波利斯，目的是评估CASE区分“喜欢”和“想要”酒精的能力，作为酒精自我管理行为的基础，为药物开发研究做准备。将比较两种CASE范例；一项评估酒精自我管理的享乐影响；另一项量化了人们为了更多的酒而工作的意愿。将在80名年轻成年饮酒者的样本人群中采用交叉设计。每个范例中的CASE表现将被评估为在启动间隔结束时对主观感知的不同敏感性，以及对酒精依赖风险因素的不同敏感性，包括家族酒精中毒史、个人近期饮酒史和酒精使用障碍症状的清单。印第安纳州还将对德国和美国样本人群进行基因分型，并寻找酒精脱氢酶簇中SNP单倍型与酒精代谢和其他危险因素之间的关联。

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.