Neuropharmacology of Abused Stimulants in Nonhuman Primates

描述（由申请人提供）：本申请中描述的职业发展和指导计划将允许申请人继续发展和扩展他的研究事业，进入新的调查领域，补充当前的专业领域。具体来说，我将有机会获得MRI功能连接和血管病理学的新技能和专业知识。我将与马克·古德曼博士合作开发新的PET生物标志物以扩大单胺转运体以外的神经药理学靶点。我还将在耶基斯野外研究站开展自我给药和PET神经成像研究以便通过与马克·威尔逊博士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内投入75%的努力，以继续推进我在药物滥用研究方面的事业，并加强我作为导师的作用。一旦所有的研究方案标准化，大约50%的努力将用于进行实验。在非人类灵长类动物中提出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相结合的灭绝疗法在恢复脑功能和防止恢复药物复发的动物模型中的有效性。这些数据将为未来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。这些非人灵长类动物的转化研究将确定血清素系统调节可卡因滥用相关行为和神经化学效应的有效性。总的来说，行为药理学、体内神经化学和功能神经影像学的整合将增强我们对非人类灵长类动物可卡因自我给药和恢复的神经生物学机制的理解。另外25%的工作将用于指导新的独立调查人员。我计划担任两名初级教师的主要导师，以及另外两名讲师或助理教授级别的教师的次要导师。通过指导具有广泛专业领域的年轻科学家，我将扩大应用于药物成瘾研究的技术和一般方法的广度。剩余的25%未得到高级科学家研究和导师奖支持的工作将致力于大学的行政责任，其他与该奖项目标一致的研究相关的追求，包括监督研究生和博士后研究员，以及教育活动。资深科学家研究和指导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颖的研究应用，并为对药物成瘾感兴趣的新独立研究者提供有效的指导。

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.