Behavioral and Neurochemical Mechanisms Underlying Stress-Precipitated Drinking

压力诱发饮酒的行为和神经化学机制

• 批准号: 10920605
• 负责人: Terril L Verplaetse
• 金额: $ 6.76万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10920605
• 关键词: Affinity; Alcohol consumption; Alcohol dependence; Alcohols; Amygdaloid structure; Anxiety; Area; Behavior; Behavioral; Behavioral Mechanisms; Binding; Brain; Brain imaging; Brain region; Clinical; Clinical Investigator; Complement; Consumption; Corticosterone; Corticotropin; Cortisone; Data; Diagnosis; Enzymes; Ethics; Etiology; Evaluation; Future; Gender; Glucocorticoid Receptor; Glucocorticoids; Goals; Hormones; Human; Hydrocortisone; Hydroxysteroid Dehydrogenases; Imagery; Imaging Techniques; Individual; Interdisciplinary Study; Intervention; Investigation; Laboratories; Lead; Maintenance; Measures; Mediator; Mentored Research Scientist Development Award; Mentors; Mentorship; Modeling; NADH dehydrogenase (ubiquinone); Neurosciences; Participant; Pharmaceutical Preparations; Positron-Emission Tomography; Pre-Clinical Model; Prefrontal Cortex; Preparation; Relapse; Reporting; Research; Research Training; Role; Scanning; Scientist; Self Administration; Sex Differences; Stress; Stressful Event; Structure; System; Techniques; Time; Training; Training Programs; Translating; Translational Research; Woman; Work; addiction; alcohol craving; alcohol intervention; alcohol research; alcohol seeking behavior; alcohol use disorder; alcohol use initiation; anxiety symptoms; career; clinical investigation; design; drinking; drinking behavior; epidemiologic data; experience; hypothalamic-pituitary-adrenal axis; innovation; insight; meetings; men; motivated behavior; neurochemistry; neuroimaging; neuromechanism; neuropsychiatry; novel; programs; radiotracer; receptor; recruit; sex; skills; social; substance use; symposium; therapy development; translational scientist

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.

项目摘要/摘要 这个指导研究科学家发展奖K 01应用程序的总体目标是提供 博士Verplaetse与必要的技能和保护的时间，成为一个独立的翻译和临床 成瘾神经科学领域的研究者。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 与社交饮酒者的对比有了这个K 01，Verplaetse博士的培训将有助于她开发和 通过更好地了解以下方面，设计酒精成瘾领域的创新研究：（1）PET 成像技术，以检查潜在的神经化学机制的压力促成的饮酒行为; (2)应激诱导技术，以评估抵抗饮酒和应激诱发酒精的能力 消费在人类实验室;（3）翻译机制，神经科学是整合与 人类实验室调查，以促进与酒精和压力有关的新的研究思路和假设 系统反应性;和{{（4）与压力相关的饮酒和相关机制的性别差异}}。的 K 01机制提供的机会将使候选人能够进行严格的，结构化的 5-一年的导师，培训和研究计划，旨在为她提供必要的技能， 以上强调的领域，并成为一个独立的研究科学家。这项研究计划将联合收割机 正式的教学培训（例如，临床研究中的伦理和实践问题课程， 神经精神病学的神经影像学），参加科学研究会议，与 导师和合作者，以及一对一的指导研究培训。为了实现这一目标，候选人 建议在三个主要领域开展进一步培训：（1）正电子发射断层扫描（PET）成像 使用一种新的放射性示踪剂测量活体人脑HPA轴反应性;（2）人类实验室 模拟压力诱发的饮酒行为;（3）高级统计培训的评估和 PET成像数据和压力诱发的饮酒数据的整合。研究部分， 协同与培训计划，重点是阐明神经化学机制的基础 应激诱发的酒精动机行为以及HPA轴和糖皮质激素系统在 有酒精使用障碍的人。Verplaetse博士的长期研究目标是使用组合PET和 人类实验室范例，以进一步了解压力诱导的酒精寻求机制 和消费，以确定酒精使用障碍的新治疗目标，重点是性别- 敏感的治疗发展。这与她的长期培训目标，即发展翻译能力， 研究技能，使她能够更好地独立领导创新和多学科的研究 关于压力诱发的饮酒行为和针对大脑压力系统的干预措施的计划。

项目成果

Sex/gender differences in brain function and structure in alcohol use: A narrative review of neuroimaging findings over the last 10 years.

• DOI: 10.1002/jnr.24625
• 发表时间: 2021-01
• 期刊: Journal of neuroscience research
• 影响因子: 4.2
• 作者: Verplaetse TL;Cosgrove KP;Tanabe J;McKee SA
• 通讯作者: McKee SA

Pharmacokinetics and Pharmacodynamics of Immediate-Release Versus Extended-Release Guanfacine in Adult Daily Smokers.

成人每日吸烟者中速释与缓释胍法辛的药代动力学和药效学。

• DOI: 10.1097/jcp.0000000000001004
• 发表时间: 2019
• 期刊: Journal of clinical psychopharmacology
• 影响因子: 2.9
• 作者: Verplaetse,TerrilL;Roberts,Walter;Moore,KellyE;Peltier,MacKenzieR;Oberleitner,LindsayM;McKee,SherryA
• 通讯作者: McKee,SherryA

Changes in excessive alcohol use among older women across the menopausal transition: a longitudinal analysis of the Study of Women's Health Across the Nation.

绝经过渡期间老年妇女过度饮酒的变化：全国妇女健康研究的纵向分析。

• DOI: 10.1186/s13293-020-00314-7
• 发表时间: 2020
• 期刊: Biology of sex differences
• 影响因子: 7.9
• 作者: Peltier,MacKenzieR;Verplaetse,TerrilL;Roberts,Walter;Moore,Kelly;Burke,Catherine;Marotta,PhillipL;Phillips,Sarah;Smith,PhilipH;McKee,SherryA
• 通讯作者: McKee,SherryA