Cocaine Sensitization and Dopamine Transporter Regulation

描述（由申请人提供）：K 05高级科学家奖的申请要求NIDA为Nancy Zahniser博士提供额外5年的支持，药理学和神经科学教授，U科罗拉多医学院。U科罗拉多以其强大的药物/酒精成瘾研究，资金记录，培训计划和合作氛围而闻名。Zahniser博士在过去4年中获得了NIDA K 05奖的支持，这对她专注于并扩大她的药物成瘾研究范围至关重要。她的研究旨在了解个体大鼠对可卡因的不同初始行为反应如何预测它们对成瘾的脆弱性，多巴胺转运蛋白（DAT）如何促成这些表型以及功能性DAT表达如何调节。最近，她开始与理查德艾伦博士进行新的合作，增强了她的实验室的行为测试曲目，包括条件位置偏好（CPP），并很快，自我管理。总的来说，她的工作表明，对可卡因的初始运动反应可以预测可卡因诱导的运动敏化和CPP的程度，这表明DAT等因素有助于不同的表型可能有助于解释奖励的个体差异。这些发现激发了她对DAT如何调节的兴趣，以及她与亚历山大索尔金博士富有成效的合作。DAT调节主要通过改变运输和细胞表面表达发生。他们的工作导致了对模型细胞系统中内吞DAT贩运期间所利用的细胞机制的新见解。他们目前正在将这些发现扩展到大脑准备。在模型系统中测试DAT假设的能力，回到大脑中，仍然是Zahniser博士工作中最重要和最独特的方面之一。持续的K 05支持将为她提供受保护的时间，专注于新的研究方向和指导，并利用她最近的领导力培训组织一个新的大学范围内的药物成瘾研究中心，整合基础，临床和治疗研究。Zahniser博士为NIDA的使命做出了贡献，他在NIDA理事会和IRP科学顾问委员会、其他成瘾中心的外部咨询委员会任职，并担任评审员。她积极指导学生，博士后研究员和初级教师谁是NIDA的支持。她的20名前学员中有10名是教师/高级研究员，他们继续独立专注于药物/酒精成瘾研究。

DESCRIPTION (provided by applicant): This application for a K05 Senior Scientist Award requests an additional 5 years of support from NIDA for Nancy Zahniser, Ph.D., Professor of Pharmacology and Neuroscience, U Colorado School of Medicine. The U Colorado is distinguished by its strong drug/alcohol addiction research, funding record, training programs and collaborative atmosphere. Dr. Zahniser's support by a NIDA K05 Award for the past 4 years has been crucial in allowing her to focus on and expand the scope of her drug addiction research. Her research seeks to understand how the differential initial behavioral responsiveness of individual rats to cocaine predicts their vulnerability to addiction, how the dopamine transporter (DAT) contributes to these phenotypes and how functional DAT expression is regulated. Recently, she began a new collaboration with Dr. Richard Allen that has enhanced her lab's behavioral testing repertoire to include conditioned place preference (CPP) and, very soon, self-administration. Overall, her work has shown that the initial locomotor response to cocaine can predict the extent of cocaine-induced locomotor sensitization and CPP, suggesting that factors like DAT that contribute to the different phenotypes may help to explain individual differences in reward. Such findings have sparked her interest in understanding how DAT is regulated and her productive collaboration with Dr. Alexander Sorkin. DAT regulation occurs largely via altered trafficking and cell surface expression. Their work has resulted in novel insights about the cellular mechanisms utilized during endocytic DAT trafficking in model cell systems. They are currently extending these findings to brain preparations. The ability to test hypotheses about DAT derived in model systems, back in the brain, remains one of the most important and unique aspects of Dr. Zahniser's work. Continued K05 support will provide her protected time to focus on new research directions and mentoring, as well as to utilize her recent leadership training in organizing a new university-wide drug addiction research center, integrating basic, clinical and treatment research. Dr. Zahniser contributed/s to NIDA's mission by serving on NIDA Council and IRP Board of Scientific Counselors, external advisory boards for other addiction centers, and as a reviewer. She is active in mentoring students, postdoctoral fellows and junior faculty who are supported by NIDA. Ten of her 20 former trainees are faculty members/senior fellows who continue independently to focus on drug/alcohol addiction research.