A translational human laboratory Pavlovian conditioning model of individual differences in risk for alcohol cue incentive salience sensitization and longitudinal assessment of problematic alcohol use

项目概要/摘要 这个K99/R 00 NIH独立之路奖将提供Dr. 神经科学家，具有两年的密集，指导培训和研究经验，在翻译 神经科学和三年的研究支持，将启动他的职业生涯作为一个独立的调查员。 培训和研究计划的重点是临床前和人类之间的双向翻译 促进酒精使用障碍（AUD）的神经行为机制的实验室模型。K99职业生涯 发展计划将提供AUD精神病理学，人类酒精管理，人类 认知/情感神经科学和人类功能性神经成像方法。培训将包括 课程、会议、个性化的一对一辅导、研讨会和讲习班。K99研究 专注于成瘾神经临床评估的神经行为领域，被认为是关键的 成瘾/AUD周期：激励显着性（IS）归因于酒精线索。临床前和人体 神经行为学证据表明，反复酒精中毒可使IS归因于酒精敏感化 线索，这可能会推动某些人的成瘾/AUD周期。为了开始测试这种可能性， Alfreesí将把个体差异的临床前模型转化为将IS归因于奖励的倾向- 将IS归因于酒精倾向的个体差异的人类实验室模型的预测线索 醉酒预测与自然奖励预测线索，并研究这些个体差异是如何 与未来酗酒问题有关。一个团队将协助阿雷西博士的发展， 跨越培训领域的集体专业知识（布鲁斯·巴塞洛夫博士、雪莉·弗拉格尔博士、布雷特·弗罗利格博士、大卫博士 Kareken，Denis McCarthy，艾德默克尔，托马斯皮亚塞基，肯尼斯谢尔，托德沙赫特曼）。K99阶段 将在密苏里州，一个世界级的研究机构，在系 心理科学，家庭对酒精和成瘾研究与人类参与者的知名教师 和一流的酒精研究培训计划（T32-AA 013526）。R 00研究将在一个未来的地方进行， 确定了R1机构，并将重点放在继续测试IS归因于酒精预测线索及其 在人类实验室中的致敏作用。这个K99/R 00奖将产生推动目标1的研究 2017-2021年NIAAA战略计划的目标1a，其中包括确定行为和神经生物学 AUD的潜在机制，并解释人们如何通过成瘾/AUD进展的异质性 周期，以便为AUD预防和治疗的发展提供信息。K99/R 00奖项还将 培养一名独立的科学家，能够并致力于进行基本的行为和神经生物学 与人类参与者的研究，将继续推进NIAAA的使命，以改善诊断， 预防和治疗酒精相关问题，包括AUD。

PROJECT SUMMARY/ABSTRACT This K99/R00 NIH Pathway to Independence Award will provide Dr. Cofresí, trained as a preclinical neuroscientist, with a two-year intensive, mentored training and research experience in translational neuroscience and three-years of research support that will launch his career as an independent investigator. The training and research program focuses on bidirectional translation between preclinical and human laboratory models of neurobehavioral mechanisms that promote alcohol use disorder (AUD). The K99 career development plan will provide training in AUD psychopathology, human alcohol administration, human cognitive/affective neuroscience, and human functional neuroimaging methods. Training will include coursework, conferences, individualized one-on-one mentoring, seminars, and workshops. The K99 research focuses on a neurobehavioral domain of the Addictions Neuroclinical Assessment believed to be critical to the Addiction/AUD Cycle: the attribution of incentive salience (IS) to alcohol cues. Preclinical and human neurobehavioral evidence suggests that repeated alcohol intoxication can sensitize IS attribution to alcohol cues, which may drive the Addiction/AUD Cycle in some individuals. To begin testing this possibility, Dr. Cofresí will translate a preclinical model of individual differences in propensity to attribute IS to reward- predictive cues into a human laboratory model of individual differences in propensity to attribute IS to alcohol intoxication-predictive vs. natural reward-predictive cues, and examine how these individual differences are associated with future problematic alcohol use. Dr. Cofresí’s development will be facilitated by a team with collective expertise spanning the areas of training (Drs. Bruce Bartholow, Shelly Flagel, Brett Froeliger, David Kareken, Denis McCarthy, Ed Merkle, Thomas Piasecki, Kenneth Sher, Todd Schachtman). The K99 phase will take place at the University of Missouri, a world-class research institution, in the Department of Psychological Sciences, home to renowned faculty in alcohol and addiction research with human participants and a premier alcohol research training program (T32-AA013526). The R00 research will take place at a to-be- determined R1 institution, and will focus on continued testing of IS attribution to alcohol-predictive cues and its sensitization in the human laboratory. This K99/R00 award will produce research that advances Goal 1 Objective 1a of the 2017-2021 NIAAA Strategic Plan, which involves identifying behavioral and neurobiological mechanisms underlying AUD, and explaining heterogeneity in how people progress through the Addiction/AUD Cycle, in order to inform the development of AUD prevention and treatment. This K99/R00 award will also produce an independent scientist able and committed to conducting basic behavioral and neurobiological research with human participants that will continue to advance NIAAA’s mission to improve diagnosis, prevention, and treatment of alcohol-related problems, including AUD.