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

• 批准号: 8475570
• 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
• 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/8475570
• 关键词: Abstinence; Agonist; Animal Model; Area; Attenuated; Award; Behavior; Behavioral; Behavioral Paradigm; Biological Markers; Blood Vessels; Brain; Cocaine; Collaborations; Commit; Complement; Cues; Data; Detection; Development; Dopamine; Dose; Drug Addiction; Drug usage; Educational Activities; Effectiveness; Exhibits; Extinction (Psychology); Faculty; Future; Goals; 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; Serotonin; Social Behavior; Substance abuse problem; System; 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; prevent; professor; public health relevance; receptor; research study; skills; stimulant abuse; therapeutic target; translational study

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指导计划将使申请人能够继续发展和扩展其研究职业生涯，以补充当前专业知识领域的新调查领域。具体来说，我将有机会通过MRI I功能连通性和血管病理获得新的技能和专业知识。我将与马克·古德曼（Mark Goodman）博士合作开发宠物的新型生物标志物，以将神经药物靶标扩大到单胺转运蛋白之外。我还将在Yerkes野战站启动自我管理和PET神经影像学研究，以通过与Mark Wilson博士的合作来关注与伦理上相关的社会行为和药物使用模型。我计划在五年的支持期间付出75％的努力，以便继续在药物滥用研究方面发展职业并增强我作为导师的角色。一旦所有研究协议都标准化，大约将大约50％的努力致力于实验的进行。提出的非人类灵长类动物的前瞻性研究将记录可卡因使用过程中发生的相关神经化学和功能变化，并运用该知识来评估药理干预措施在标准化脑功能和防止作为药物复发动物模型恢复的药理干预方面增强的灭绝疗法的有效性。这些数据将为未来药物开发的药理目标提供见解，从而加快发现有效治疗的发现。相关的研究将提供有关5-羟色胺在与可卡因神经药理有关的多巴胺能功能调节中的基本作用的信息。这些非人类灵长类动物的翻译研究将确定5-羟色胺系统调节可卡因与滥用相关的行为和神经化学作用的有效性。总体而言，行为药理学，体内神经化学和功能性神经影像的整合将增强我们对可卡因自我给药和恢复非人类灵长类动物的神经生物学机制的理解。另有25％的努力将致力于指导新的独立研究人员。我计划担任两位初级教职员工的主要导师，并担任两位教师或助理教授的另外两位教职员工的次要导师。通过指导年轻的科学家具有广泛的专业领域，我将扩大针对药物成瘾研究的技术和一般方法的广度。剩下的25％的努力不受高级科学家研究和指导奖的支持，将承担大学行政职责，其他与研究相关的追求与奖项的目标一致，包括对研究生和博士后研究员的监督以及教育活动。高级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实施给新的研究应用，并为对吸毒兴趣兴趣的新独立研究人员提供有效的指导。