Cocaine Sensitization and Dopamine Transporter Regulation

可卡因致敏和多巴胺转运蛋白调节

• 批准号: 7808755
• 负责人: Nancy Rutledge Zahniser
• 金额: $ 12.54万
• 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 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7808755
• 关键词: Alcoholism; Alcohols; Amphetamines; Back; Behavior; Behavioral; Biological Models; Brain; Brain-Derived Neurotrophic Factor; Candidate Disease Gene; Cell model; Cell surface; Clinical Treatment; Cocaine; Collaborations; Colorado; Corpus striatum structure; Doctor of Medicine; Doctor of Philosophy; Dopamine; Drug Addiction; Endocytosis; Ethanol; Faculty; Fluorescence Resonance Energy Transfer; Funding; Grant; Hearing; Hippocampus (Brain); Human; Inbred Mouse; Individual; Individual Differences; Leadership; Link; Manuscripts; Maps; Mentors; Microscopy; Mission; Motor Activity; Mus; N-Methyl-D-Aspartate Receptors; NMDA receptor 2B; National Institute of Drug Abuse; Neurosciences; Paper; Pharmaceutical Preparations; Pharmacology; Phenotype; Postdoctoral Fellow; Preparation; Professional counselor; Protein Tyrosine Kinase; Publishing; RNA Interference; Rat Strains; Rattus; Recombinants; Regulation; Research; Rewards; Role; Self Administration; Senior Scientist Award; Sleep; Sprague-Dawley Rats; Students; System; Testing; Time; Toxic effect; Training; Training Programs; Tyrosine; Tyrosine Kinase Inhibitor; Universities; Work; abstracting; addiction; alcohol sensitivity; behavior test; dopamine transporter; in vivo; insight; interest; male; medical schools; member; mouse model; nerve stem cell; novel; planetary Atmosphere; preference; professor; programs; research study; response; trafficking; ziprasidone

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.

描述（由申请人提供）：本 K05 高级科学家奖申请请求 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。科罗拉多大学以其强大的药物/酒精成瘾研究、资助记录、培训项目和合作氛围而闻名。 Zahniser 博士过去 4 年获得 NIDA K05 奖的支持对于她能够专注于并扩大毒瘾研究范围至关重要。她的研究旨在了解老鼠对可卡因的不同初始行为反应如何预测其成瘾的脆弱性、多巴胺转运蛋白 (DAT) 如何促成这些表型以及功能性 DAT 表达如何受到调节。最近，她开始与 Richard Allen 博士进行新的合作，增强了她实验室的行为测试能力，包括条件性位置偏好 (CPP) 以及很快的自我管理。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化和 CPP 的程度，这表明 DAT 等导致不同表型的因素可能有助于解释奖励的个体差异。这些发现激发了她了解 DAT 监管方式的兴趣，并激发了她与 Alexander Sorkin 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来实现。他们的工作对模型细胞系统中内吞 DAT 运输过程中所使用的细胞机制产生了新的见解。他们目前正在将这些发现扩展到大脑准备工作中。测试来自大脑模型系统中 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。持续的 K05 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，并利用她最近接受的领导力培训来组织一个新的全校范围内的毒瘾研究中心，整合基础、临床和治疗研究。 Zahniser 博士在 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，为 NIDA 的使命做出了贡献。她积极指导 NIDA 支持的学生、博士后研究员和初级教师。她的 20 名前学员中有 10 名是教职人员/高级研究员，他们继续独立专注于药物/酒精成瘾研究。