Cocaine Sensitization & Dopamine Transporter Regulation

描述：(申请人提供)： NIDA的这份新的K05高级科学家奖申请请求为5 多年来对南希·R·扎尼瑟博士、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；良好的资金记录；科学影响；以及协作 大气层。Zahniser博士曾因以下原因获得过NIDA“K02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，让她 不仅要专注于药物滥用研究，而且要扩大她的研究范围 研究。例如，她早期的研究表明，多巴胺转运体 (DAT)有助于持续表达可卡因诱导的行为 敏化。她帮助开发了新的电化学记录技术 同时测量体内DAT活性的指标--DA清除量，以及 自由活动大鼠的行为。她和她的研究生现在已经使用了这个 方法来确认这一关系。因此，只有表现出 可卡因引起的DAT改变也表现出行为敏化。 这项技术的发展对她最近收到了一份 荣誉奖，以支持她的工作。这些结果使她实现了长期目标 了解大脑中的DAT调节。她已经确定了膜 调节DAT的潜能、蛋白激酶、DA D2受体和底物 活动性和表现力。她的结果，和其他实验室的结果一样，表明 DAT调控在很大程度上是通过细胞表面表达的变化进行的。因此，她 发起与亚历山大·索尔金博士的合作，研究 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转运。这 K05奖将为她提供“受保护的时间”来专注于这一新方向，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，所有这些都将显著 为她的事业发展和药物滥用领域做出贡献。其中最 她工作的重要而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，并回到大脑中。Dr。 Zahniser也一直为药物滥用领域做出贡献，他在 赠款/手稿，担任咨询小组成员并组织 座谈会/会议。她积极参加训练。她之前的14名毕业生中有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 独立学院的调查人员。她目前的5名实习生都在努力 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.