Cocaine Sensitization and Dopamine Transporter Regulation

描述(由申请者提供)：本K05高级科学家奖申请书要求NIDA为科罗拉多大学医学院药理学和神经科学教授Nancy Zahniser博士提供额外5年的支持。科罗拉多州大学以其强大的药物/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 K05奖的支持，这对她专注于并扩大她的毒瘾研究范围至关重要。她的研究试图了解单个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易感性，多巴胺转运体(DAT)如何对这些表型做出贡献，以及DAT功能表达是如何受到调节的。最近，她与理查德·艾伦博士开始了一项新的合作，增强了她的实验室的行为测试曲目，包括条件位置偏好(CPP)，很快还包括自我管理。总体而言，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感化和CPP的程度，这表明像DAT这样导致不同表型的因素可能有助于解释奖励的个体差异。这些发现激发了她对了解DAT是如何被监管的兴趣，以及她与Alexander Sorkin博士富有成效的合作。DAT调控主要是通过改变运输和细胞表面表达来进行的。他们的工作导致了对在模型细胞系统中内吞DAT过程中所使用的细胞机制的新的见解。他们目前正在将这些发现扩展到大脑制剂。在模型系统和大脑中测试有关DAT的假设的能力，仍然是Zahniser博士工作中最重要和最独特的方面之一。K05的持续支持将为她提供受保护的时间，让她专注于新的研究方向和指导，并利用她最近的领导能力培训，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/S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顾问委员会任职，并担任审查员。她积极指导NIDA支持的学生、博士后研究员和初级教员。在她之前的20名实习生中，有10名是教职员工/高级研究员，他们继续独立地专注于毒品/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.