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

酒精提示诱因显着性敏感性和有问题的酒精使用的纵向评估风险个体差异的转化人类实验室巴甫洛夫调节模型

• 批准号: 10371738
• 负责人: Roberto U Cofresi
• 金额: $ 16.47万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10371738
• 关键词: Address; Adult; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcoholic Beverages; Alcoholic Intoxication; Alcohols; Area; Award; Behavioral; Behavioral Mechanisms; Brain; Clinical; Cognitive; Conditioned Reflex; Cues; Desire for food; Development; Development Plans; Diagnosis; Disease; Educational workshop; Electroencephalography; Etiology; Event-Related Potentials; Exhibits; Faculty; Functional Magnetic Resonance Imaging; Future; Goals; Heavy Drinking; Heterogeneity; Home; Human; Incentives; Individual; Individual Differences; Institution; Knowledge; Laboratories; Learning; Link; Literature; Measurable; Measures; Mentors; Methods; Mission; Missouri; Modeling; Motivation; National Institute on Alcohol Abuse and Alcoholism; Neurobiology; Nucleus Accumbens; Participant; Pathway interactions; Persons; Phase; Phenotype; Population; Positioning Attribute; Pre-Clinical Model; Prevention; Psychopathology; Public Health; Recording of previous events; Research; Research Personnel; Research Support; Rewards; Role; Sampling; Science; Scientist; Signal Transduction; Smell Perception; Strategic Planning; System; Taste Perception; Testing; Time; Training; Training Programs; Translating; Translations; United States; United States National Institutes of Health; Universities; Variant; Vision; Visit; Visual; Work; addiction; affective neuroscience; alcohol abuse therapy; alcohol cue; alcohol involvement; alcohol related problem; alcohol research; alcohol reward; alcohol risk; alcohol sensitivity; alcohol use disorder; blood oxygenation level dependent response; career; career development; classical conditioning; clinical development; conditioning; craving; cue reactivity; disorder prevention; disorder risk; efficacious treatment; experience; improved; incentive salience; neural circuit; neurobehavioral; neurobiological mechanism; neuroimaging; neurophysiology; peer; post-doctoral training; pre-clinical; preference; programs; psychologic; skills; sugar; symposium; theories; translational neuroscience

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.

项目概要/摘要 K99/R00 NIH 独立之路奖将为 Cofresí 博士提供临床前培训 神经科学家，在转化方面拥有两年的密集指导培训和研究经验 神经科学和三年的研究支持将开启他作为独立研究者的职业生涯。 培训和研究计划侧重于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。 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神经影像方法培训将包括。 课程、会议、个性化一对一指导、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，该领域被认为对于成瘾至关重要 成瘾/AUD 循环：将激励显着性 (IS) 归因于临床前和人类。 神经行为证据表明，反复酒精中毒会使 IS 对酒精的归因变得敏感 提示，这可能会导致某些人的成瘾/澳元循环。为了开始测试这种可能性，博士。 Cofresí 将转化个体差异倾向的临床前模型，将 IS 归因于奖励- 人类实验室模型中个体差异倾向的预测线索将IS归因于酒精 中毒预测线索与自然奖励预测线索，并检查这些个体差异是如何产生的 与未来有问题的饮酒相关的问题将由一个团队来促进 Cofresí 博士的发展。 跨越培训领域的集体专业知识（Bruce Bartholow 博士、Shelly Flagel、Brett Froeliger、David Kareken、Denis McCarthy、Ed Merkle、Thomas Piasecki、Kenneth Sher、Todd Schachtman）。 将在世界一流的研究机构密苏里大学的系中进行 心理科学，拥有从事人类参与者酒精和成瘾研究的著名教员 以及首要的酒精研究培训计划（T32-AA013526）。 确定了 R1 机构，并将重点继续测试 IS 归因于酒精预测线索及其 该 K99/R00 奖项将产生推进目标 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，并解释人们如何克服成瘾/AUD 的异质性 循环，以便为 AUD 预防和治疗的发展提供信息。该 K99/R00 奖项也将颁发。 培养一位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， 预防和治疗与酒精相关的问题，包括 AUD。