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Neuropharmacology of Abused Stimulants in Nonhuman Primates

非人类灵长类动物滥用兴奋剂的神经药理学

基本信息

批准号：
9094694
负责人：
LEONARD L HOWELL
金额：
$ 12.37万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-06-01 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9094694
关键词：
Abstinence Agonist Animal Model Area Attenuated Award Behavior Behavioral Behavioral Paradigm Blood Vessels Brain Cocaine Collaborations Complement Cues Data Detection Development Dopamine Dose Drug Addiction Drug usage Educational Activities Effectiveness Exhibits Extinction (Psychology)Faculty Future Goals Health Intake Intervention Investigation Knowledge Magnetic Resonance Imaging Mentors Mentorship Modeling Monkeys N-Methylaspartate Neuropharmacology Pathology Pharmaceutical Preparations Positron-Emission Tomography Postdoctoral Fellow Prospective Studies Protocols documentation Psychostimulant dependence Regulation Research Research Personnel Rest Role Scientist Self Administration Senior Scientist Serotonergic System Serotonin Social Behavior Substance abuse problem Techniques Training Universities addiction attenuation behavioral pharmacology brain metabolism career career development cocaine use drug abstinence drug relapse effective therapy graduate student in vivo inhibitor/antagonist insight instructor interest monoamine neurobiological mechanism neurochemistry neuroimaging nonhuman primate novel novel marker prevent professor receptor research study skills stimulant abuse therapeutic target translational study

项目摘要

DESCRIPTION (provided by applicant): The career development and mentorship plan described in this application will allow the applicant to continue the development and expansion of his research career into new areas of investigation that complement current areas of expertise. Specifically, I will have the opportunity to acquire new skills and expertise with MRI i functional connectivity and vascular pathology. I will collaborate with Dr. Mark Goodman on the development of novel biomarkers for PET in order to expand neuropharmacological targets beyond monoamine transporters. I also will initiate self-administration and PET neuroimaging studies at the Yerkes Field Station in order to focus on ethologically-relevant models of social behavior and drug use through collaboration with Dr. Mark Wilson. I plan to commit 75% effort during the five-year period of support in order to continue to advance my career in substance abuse research and enhance my role as a mentor. Approximately 50% effort will be devoted to the conduct of experiments once all research protocols are standardized. The proposed prospective studies in nonhuman primates will document the relevant neurochemical and functional changes that occur during cocaine use and apply this knowledge to evaluate the effectiveness of extinction therapy augmented with pharmacological intervention in normalizing brain function and preventing reinstatement as an animal model of drug relapse. These data will provide insights on pharmacological targets for future medications development, thus accelerating the discovery of effective treatments. Related studies will provide information concerning the basic role of serotonin in the regulation of dopaminergic function as it relates to the neuropharmacology of cocaine. These translational studies in nonhuman primates will determine the effectiveness of the serotonin system to modulate the abuse-related behavioral and neurochemical effects cocaine. Collectively, the integration of behavioral pharmacology, in vivo neurochemistry and functional neuroimaging will enhance our understanding of the neurobiological mechanisms involved in cocaine self- administration and reinstatement in nonhuman primates. Another 25% effort will be committed to mentoring of new, independent investigators. I plan to serve as the primary mentor of two junior faculty and as a secondary mentor for two additional faculty at the rank of Instructor or Assistant Professor. Through mentoring young scientists with broad areas of expertise, I will expand the breadth of techniques and general approaches applied to drug addiction research. The remaining 25% effort not supported by the Senior Scientist Research and Mentorship Award will be committed to University administrative responsibilities, other research-related pursuits consistent with the objectives of the award, including oversight of graduate students and postdoctoral fellows, and educational activities. The long-term commitment and support provided by a Senior Scientist Research and Mentorship Award will allow the implementation of these integrated techniques to novel research applications, and provide effective mentorship for new, independent investigators with an interest in drug addiction.

描述（由申请人提供）：本申请中描述的职业发展和导师计划将使申请人能够继续发展和扩展他的研究生涯，进入新的调查领域，以补充当前的专业领域。具体来说，我将有机会获得MRI i功能连接和血管病理学方面的新技能和专业知识。我将与Mark Goodman博士合作开发PET的新型生物标志物，以扩大单胺转运体以外的神经药理学靶点。我还将在Yerkes野外站启动自我管理和PET神经成像研究，以便通过与Mark Wilson博士的合作，专注于社会行为和药物使用的行为学相关模型。我计划在五年的支持期间投入75%的努力，以继续推进我在药物滥用研究方面的职业生涯，并加强我作为导师的作用。一旦所有研究方案标准化，大约50%的努力将用于实验的进行。拟在非人灵长类动物中进行的前瞻性研究将记录可卡因使用期间发生的相关神经化学和功能变化，并将这些知识应用于评估药物干预增强的消退治疗在恢复脑功能和预防复发方面的有效性，作为药物复发的动物模型。这些数据将为未来的药物开发提供药理学靶点的见解，从而加速发现有效的治疗方法。相关研究将提供有关血清素在调节多巴胺能功能中的基本作用的信息，因为它与可卡因的神经药理学有关。这些在非人类灵长类动物中的转化研究将确定5-羟色胺系统调节可卡因滥用相关行为和神经化学作用的有效性。总的来说，行为药理学、体内神经化学和功能性神经成像的整合将增强我们对非人灵长类动物中可卡因自我给药和恢复所涉及的神经生物学机制的理解。另外25%的努力将致力于指导新的独立调查人员。我计划担任两个初级教师的主要导师，并作为二级导师的两个额外的教师在讲师或助理教授的职级。通过指导具有广泛专业领域的年轻科学家，我将扩大适用于药物成瘾研究的技术和一般方法的广度。其余25%的努力不支持高级科学家研究和导师奖将致力于大学的行政责任，其他研究相关的追求与奖励的目标一致，包括研究生和博士后研究员的监督，和教育活动。高级科学家研究和导师奖提供的长期承诺和支持将允许将这些综合技术应用于新的研究应用，并为对药物成瘾感兴趣的新的独立调查人员提供有效的导师。