Cocaine Sensitization & Dopamine Transporter Regulation

描述：（申请人提供）： 这一新的申请“K 05高级科学家奖”从NIDA要求5 多年来对南希的支持。Zahniser博士，药理学教授， 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;强大的资金记录;科学影响;和协作 气氛Zahniser博士曾获得NIDA“K 02独立科学家奖”， 在过去的9年里，这种支持对她的职业生涯至关重要， 不仅要关注药物滥用研究，而且要扩大她的范围， research.例如，她的早期研究表明多巴胺转运蛋白 (DAT)有助于持续表达可卡因诱导的行为 致敏她帮助开发了新的电化学记录技术 同时测量DA清除率，体内DAT活性的测量，和 自由移动的老鼠的行为。她和她的研究生现在已经用这个 方法来确认这种关系。因此，只有表现出 可卡因诱导的DAT变化也表现出行为敏化。 这项技术的发展有助于她最近获得 优秀奖，以支持她的工作。这些结果导致了她的长期目标 理解DAT在大脑中的调节。她已经识别出膜 潜在的，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。所以她 发起了与亚历山大索尔金博士的合作， 分子机制和蛋白质-蛋白质相互作用， 模型细胞系统和神经元制备物中的内吞DAT运输。这 K 05奖将为她提供“受保护的时间”，专注于这个新的方向， 以及研究DAT在干细胞中表达/功能的新项目， 可卡因敏感和不敏感的小鼠，所有这些都将显着 有助于她的职业发展和药物滥用领域。一个最 她的工作的重要和独特的方面是测试的愿望和能力 关于DAT的假设，来自模型系统，回到大脑中。博士 Zahniser也一直致力于药物滥用领域的审查 赠款/手稿，在咨询小组任职， 专题讨论会/会议。她积极参加训练。她14个毕业生中的6个 学生和博士后研究员现在正在进行药物滥用/酒精研究， 独立教师调查员。她现在的5个实习生都在 药物滥用/酒精研究项目。

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.