Translational models of brain activation patterns during nicotine self-administration and reinstatement

 描述(申请人提供)：神经成像方法已经成为神经科学研究中越来越重要的工具，为理解与药物作用相关的神经底物提供了一种手段。这一K01奖项将为斯蒂芬·科胡特博士获得更多经验和指导提供支持和保护时间，这些经验和指导将通过获得药理学磁共振成像(PhMRI)方面的新技能，补充和扩大他在临床前IV药物自我给药和药物测试方面的现有专业知识。在拟议的获奖期内，PI将首先完成一项强化培训计划，以发展设计、实施和分析phMRI研究所需的核心技能和知识。培训将在麦克莱恩成像中心和马萨诸塞州综合医院进行，包括课程作业和研讨会，以及与世界知名的指导团队的讨论和会议，以促进完成一个创新的研究项目。该研究项目的一个主要优势是，它将通过一系列系统的实验来优化PI的训练体验，这些实验评估了在实验室中典型的药物成瘾阶段的神经功能，包括IV自我给药(即吸毒)和恢复(即复发)，以及在非人类灵长类动物(NHP)中新的治疗方法(药理学和/或行为)的影响。这项将对该领域产生重大影响的研究计划的另一个主要优势是，它涉及使用清醒行为NHP来研究尼古丁自我给药和恢复尼古丁的功能后果，以及它们在治疗期间如何改变。多个大脑区域的大脑功能活动将直接与正在进行的“实时”行为有关，这些行为可以在行为会话内和跨行为会话进行测量。通过研究计划，将在3Tesla(3T)进行phMRI的重点研究培训，但PI还将接受关于最先进的、超高场9.4T磁体的培训，该磁体足够大 以适应国家核电计划。临床现场力量(3T)训练与超高现场力量(9.4T)训练相结合，将使应聘者具备知识和技能 有必要成为R01资助的独立研究员，站在与行为和大脑功能相关的真正翻译成瘾研究的前沿。总体而言，这一培训经验将使候选人能够开发一种新的调查方法，以检查新的治疗方法如何在吸毒和复发期间影响尼古丁和其他滥用药物的各种神经元影响，并将使PI成为一名独立的科学家，他有资格进行高度翻译成瘾的研究，以解决 需要训练有素的调查人员，他们可以探索药物滥用和成瘾的神经关联。

 DESCRIPTION (provided by applicant): Neuroimaging methodologies have become increasingly important tools in neuroscience research, providing a means for understanding the neural substrates related to drug action. This K01 Award will provide support and protected time for Dr. Stephen Kohut to obtain additional experience and mentoring that will complement and expand his existing expertise in preclinical IV drug self-administration and medication testing by acquiring new skills in pharmacologic magnetic resonance imaging (phMRI). During the proposed award period the PI will first complete an intensive training program to develop the core skills and knowledge necessary to design, conduct, and analyze phMRI studies. Training will occur at the McLean Imaging Center and Massachusetts General Hospital and will involve coursework and seminars, and discussions and meetings with a world-renowned mentoring team that will facilitate completion of an innovative research project. A major strength of the research project is that it will optimize the PI's training experience through a systematic series f experiments evaluating neuronal function during the phases of drug addiction typically modeled in the laboratory including IV self-administration (i.e., drug-taking) and reinstatement (i.e., relapse) and the effects of novel treatment approaches (pharmacological and/or behavioral) in non-human primates (NHP). Another major strength of the research plan, which will have a major impact on the field, is that it involves the use of awake, behaving NHP to study the functional consequences of nicotine self-administration and reinstatement and how they are altered during treatment. Functional brain activity in multiple brain regions will be directly relaed to ongoing "real time" behavior that can be measured within and across behavioral sessions. Focused research training in phMRI will occur at 3 Tesla (3T) through the Research Plan, but the PI will also receive training on a state-of-the-art, ultra-high field 9.4T magnet, large enough to accommodate NHP. The combination of training at clinical field strength (3T) coupled with training at ultra-high field strength (9.4T) will equip the Candidate with the knowledge and skills necessary to become an R01-funded independent investigator at the forefront of truly translational addiction research relating behavior and brain function. Overall, this training experience will allow the Candidate to develop a novel investigative approach for examining how novel treatments influence the various neuronal effects of nicotine and other drugs of abuse during periods of drug-taking and relapse, and will establish the PI as an independent scientist who is qualified to conduct highly translational addiction research that will address the need for highly trained investigators who can explore the neural correlates of drug abuse and addiction.