Behavioral and Neurochemical Mechanisms Underlying Stress-Precipitated Drinking

项目摘要/摘要 此指导研究科学家发展奖K01应用程序的总体目标是提供 Verplaetse博士拥有必要的技能和受保护的时间来成为独立的翻译和临床医生 成瘾神经科学领域的研究人员。Verplaetse博士的研究将集中在行为和 饮酒者应激诱发饮酒行为的神经化学机制 失调症与社交饮酒者。有了K01，Verplaetse博士的培训将帮助她发展和 通过更好地了解以下内容来设计酒精成瘾领域的创新研究：(1)PET 成像技术，以检查压力沉淀饮酒行为背后的神经化学机制； (2)压力诱导技术，以评估抵抗饮酒和压力沉淀酒精的能力 人体实验室中的消耗；(3)神经科学与 促进与酒精和压力相关的新研究想法和假设的人体实验室调查 系统反应性；以及{(4)与压力相关的饮酒及相关机制的性别差异}}。这个 K01机制提供的机会将使应聘者能够开始严格的、结构化的 为期5年的指导、培训和研究计划，旨在为她提供必要的技能 在上面强调的领域，并成为一名独立的研究科学家。这项研究计划将结合 正规教学培训(例如，关于临床调查和临床研究的伦理和实践问题的课程 神经精神病学中的神经成像)，出席科学研究会议，与 导师和合作者，以及一对一的导师研究培训。为了追求这一目标，候选人 提议在三个主要领域开展进一步培训：(1)正电子发射断层成像 使用一种新型放射性示踪剂测量活体人脑中HPA轴的反应性；(2)人类实验室 建立压力沉淀饮酒行为的模型；以及(3)高级统计培训，用于评估和 PET成像数据和压力沉淀饮酒数据的整合。研究部分，即 与培训计划的协同作用，侧重于阐明潜在的神经化学机制 应激-酒精激发行为及HPA轴和糖皮质激素系统在脑损伤中的作用 有酒精使用障碍的人。Verplaetse博士的长期研究目标是将PET和 进一步了解压力诱发酒精寻求的潜在机制的人类实验室范式 和消费，以确定酒精使用障碍的新治疗目标，重点是性别- 敏感的治疗进展。这与她的长期培训目标相结合，即开发翻译 研究技能，使她能够更好地独立领导创新和多学科的研究 以大脑应激系统为目标的应激诱发饮酒行为和干预方案。

PROJECT SUMMARY/ABSTRACT The overarching goal of this Mentored Research Scientist Development Award K01 application is to provide Dr. Verplaetse with the requisite skills and protected time to become an independent translational and clinical investigator in the field of addiction neuroscience. Dr. Verplaetse's research will focus on the behavioral and neurochemical mechanisms underlying stress-precipitated drinking behaviors in individuals with alcohol use disorders versus social drinkers. With this K01, Dr. Verplaetse's training will assist her in developing and designing innovative research in the field of alcohol addiction by gaining a better understanding of: (1) PET imaging techniques to examine neurochemical mechanisms underlying stress-precipitated drinking behavior; (2) techniques for stress induction to assess the ability to resist drinking and stress-precipitated alcohol consumption in the human laboratory; (3) translational mechanisms by which neuroscience is integrated with human laboratory investigations to facilitate novel research ideas and hypotheses related to alcohol and stress system reactivity; and {{{(4) sex differences in stress-related drinking and associated mechanisms}}}. The opportunities afforded by the K01 mechanism would enable the candidate to embark on a rigorous, structured 5-year program of mentorship, training, and research, designed to provide her with the necessary skills in the areas highlighted above and to become an independent research scientist. This program of study will combine formal didactic training (e.g., courses on Ethical and Practical Issues in Clinical Investigation and Neuroimaging in Neuropsychiatry), attendance to scientific research conferences, structured meetings with mentors and collaborators, and one-on-one mentored research training. In pursuit of this goal, the candidate proposes to undertake further training in three primary areas: (1) positron emission tomography (PET) imaging using a novel radiotracer to measure HPA axis reactivity in the living human brain; (2) human laboratory modeling of stress-precipitated drinking behavior; and (3) advanced statistical training for the evaluation and integration of PET imaging data and stress-precipitated drinking data. The research component, which is synergistic with the training program, is focused on the elucidation of neurochemical mechanisms underlying stress-precipitated alcohol-motivated behaviors and the role of the HPA axis and glucocorticoid systems in individuals with alcohol use disorders. Dr. Verplaetse's long-term research goal is to use a combined PET and human laboratory paradigm to further understand the mechanisms underlying stress-induced alcohol-seeking and consumption to identify novel treatment targets for alcohol use disorders, with an emphasis on gender- sensitive treatment development. This interfaces with her long-term training goal of developing translational research skills that will better enable her to independently lead an innovative and multidisciplinary research program on stress-precipitated drinking behaviors and interventions targeting the brain stress systems.