Cocaine Sensitization & Dopamine Transporter Regulation

可卡因致敏

• 批准号: 6887652
• 负责人: Nancy Rutledge Zahniser
• 金额: $ 12.15万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6887652
• 关键词: HeLa cells; Xenopus oocyte; autoradiography; behavioral /social science research tag; behavioral habituation /sensitization; cocaine; corpus striatum; dopamine transporter; electrochemistry; endocytosis; fluorescence resonance energy transfer; high performance liquid chromatography; laboratory rat; mutant; neuroregulation; protein kinase C; protein protein interaction; substantia nigra; tissue /cell culture

DESCRIPTION: (Provided by Applicant): This new application for a "K05 Senior Scientist Award" from NIDA requests 5 years of support for Nancy R. Zahniser, Ph.D., Professor of Pharmacology, University of Colorado School of Medicine. The Department of Pharmacology is distinguished by its strengths in neuropharmacology, alcohol and drug abuse research; strong funding record; scientific impact; and collaborative atmosphere. Dr. Zahniser has had a NIDA "K02 Independent Scientist Award" for the past 9 years, and this support has been crucial to her career, allowing her not only to focus on drug abuse research but also to expand the scope of her research. For example, her early work suggested that the dopamine transporter (DAT) contributes to persistent expression of cocaine-induced behavioral sensitization. She helped to develop new electrochemical recording technology to measure concurrently DA clearance, a measure of in vivo DAT activity, and behavior in freely-moving rats. She and her graduate student have now used this method to confirm this relationship. Thus, only rats that showed cocaine-induced changes in DAT also exhibited behavioral sensitization. Development of this technology was instrumental in her recently receiving a MERIT Award to support her work. These results have lead to her long-term goal of understanding DAT regulation in the brain. She has identified membrane potential, protein kinases, DA D2 receptors and substrates as regulating DAT activity and expression. Her results, like those from other labs, suggest that DAT regulation occurs largely via changes in cell surface expression. Thus, she initiated a collaboration with Dr. Alexander Sorkin to study the basic molecular machinery and protein-protein interactions that occur during endocytic DAT trafficking in model cell systems and neuronal preparations. This K05 Award will provide her "protected time" to focus on this new direction, as well as on new projects studying DAT expression/function in stem cells and in cocaine-sensitive and -insensitive mice, all of which will significantly contribute to her career development and the drug abuse field. One of the most important and unique aspects of her work is the desire and ability to test hypotheses about DAT, derived from model systems, back in the brain. Dr. Zahniser has also consistently contributed to the drug abuse field by reviewing grants/manuscripts, serving on advisory panels and organizing symposia/meetings. She is active in training. Six of her 14 former graduate students and postdoctoral fellows are now doing drug abuse/alcohol research as independent faculty investigators. All 5 of her current trainees are working on drug abuse/alcohol research projects.

描述：（由申请人提供）： NIDA 的“K05 高级科学家奖”新申请要求 5 多年来对药理学教授 Nancy R. Zahniser 博士的支持， 科罗拉多大学医学院。药理学系是 以其在神经药理学、酒精和药物滥用方面的优势而闻名 研究;良好的融资记录；科学影响；和协作 气氛。 Zahniser 博士因以下原因荣获 NIDA“K​​02 独立科学家奖” 过去 9 年里，这种支持对她的职业生涯至关重要，使她能够 不仅要专注于药物滥用研究，还要扩大她的研究范围 研究。例如，她的早期工作表明多巴胺转运蛋白 （DAT）有助于可卡因诱导的行为的持续表达 敏化。她帮助开发了新的电化学记录技术 同时测量 DA 清除率，衡量体内 DAT 活性，以及 自由活动的大鼠的行为。她和她的研究生现在已经使用了这个 方法来确认这种关系。因此，只有老鼠表现出 可卡因引起的 DAT 变化也表现出行为敏感性。 这项技术的发展有助于她最近获得 优异奖以支持她的工作。这些结果实现了她的长期目标 了解大脑中 DAT 的调节。她已经鉴定出膜 潜力、蛋白激酶、DA D2 受体和底物作为调节 DAT 活动和表达。与其他实验室的结果一样，她的结果表明 DAT 调节主要通过细胞表面表达的变化发生。于是，她 与 Alexander Sorkin 博士合作研究基础 分子机制和蛋白质-蛋白质相互作用发生在 模型细胞系统和神经元制剂中的内吞 DAT 运输。这 K05奖将为她提供“受保护的时间”来专注于这个新方向，因为 以及研究干细胞中 DAT 表达/功能的新项目 对可卡因敏感和不敏感的小鼠，所有这些都会显着 为她的职业发展和药物滥用领域做出贡献。最有之一 她工作中重​​要且独特的方面是测试的愿望和能力 关于 DAT 的假设，源自模型系统，返回大脑。博士。 Zahniser 还通过审查不断为药物滥用领域做出贡献 赠款/手稿，在顾问小组中任职并组织 研讨会/会议。她积极参加训练。她 14 名前毕业生中的 6 名 学生和博士后研究员现在正在进行药物滥用/酒精研究 独立的教师调查员。她目前的 5 名练习生都在从事 药物滥用/酒精研究项目。