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

项目摘要/摘要 这项K99/R00 NIH独立之路奖将为科弗雷斯博士提供临床前培训 神经学家，在翻译方面有两年的强化指导培训和研究经验 神经科学和三年的研究支持，这将开启他作为独立调查员的职业生涯。 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 发展计划将提供澳大利亚精神病理学、人类酒精管理、人类 认知/情感神经科学和人类功能神经成像方法。培训将包括 课程作业、会议、个性化的一对一指导、研讨会和研讨会。K99研究 重点关注成瘾的神经行为领域神经临床评估被认为对成瘾 成瘾/AUD循环：激励性显著(IS)归因于酒精暗示。临床前和人类 神经行为证据表明，反复酒精中毒可使酒精敏感 提示，这可能会驱动一些人的上瘾/AUD循环。为了开始测试这种可能性，他说。 Cofresí将翻译一个临床前模型，即个体在归因倾向上的差异是奖励- 进入人体实验室模型的个体归因倾向差异的预测性线索是酒精 醉酒-预测与自然奖励-预测线索，并检查这些个体差异是如何 与未来有问题的酒精使用有关。科弗雷斯博士S的发展将由一个团队提供帮助，该团队将与 培训领域的集体专业知识(Bruce Bartholow博士、Shelly Flagel博士、Brett Froig er博士、David博士 卡雷肯、丹尼斯·麦卡锡、埃德·默克尔、托马斯·皮亚塞基、肯尼斯·谢尔、托德·沙赫特曼)。K99阶段 将在密苏里大学举行，这是一个世界级的研究机构，位于 心理科学，著名的酒精和成瘾研究教师的大本营，有人类参与者 和一个主要的酒精研究培训计划(T32-AA013526)。R00研究将在一个未来的- 确定了R1机构，并将专注于继续测试IS归因于酒精预测线索及其 人体实验室中的敏化作用。该K99/R00奖将产生推进目标1的研究 2017-2021年NIAAA战略计划的目标1a，其中涉及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进步的异质性 周期，以告知AUD预防和治疗的发展情况。这个K99/R00奖也将 培养一名能够并致力于进行基本行为和神经生物学研究的独立科学家 与人类参与者的研究将继续推进NIAAA改善诊断的使命， 预防和治疗与酒精有关的问题，包括澳元。

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.