Career Development Award

职业发展奖

• 批准号: 8637027
• 负责人: ANNETTE FLECKENSTEIN
• 金额: $ 13.22万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8637027
• 关键词: Acute; Adolescent; Affect; Amphetamines; Animals; Award; Clinical; Cocaine; Cocaine Abuse; Complex; Cytoplasm; Data; Development; Dopamine; Dose; Drug abuse; Drug usage; Event; Funding; Health; Human; Independent Scientist Award; Individual; Injection of therapeutic agent; Investigation; K-Series Research Career Programs; Kinetics; Laboratories; Location; Mediating; Membrane; Methamphetamine; Methylphenidate; Neurons; Pattern; Pharmaceutical Preparations; Pharmacology and Toxicology; Principal Investigator; Process; Property; Public Health; Rattus; Regulation; Reporting; Research; Research Personnel; Residual state; Rodent; Self Administration; Self-Administered; Staging; Subcellular Fractions; Synaptosomes; Technology; Testing; Time; Universities; Utah; Vesicle; clinically relevant; dopamine transporter; insight; methamphetamine abuse; methamphetamine exposure; neurotoxic; neurotoxicity; new technology; novel; professor; programs; psychostimulant; stimulant abuse; vesicular monoamine transporter 2

DESCRIPTION (provided by applicant): This is a Career Development Award proposal for Dr. Annette Fleckenstein. She is a Professor of Pharmacology and Toxicology at the University of Utah. She has been active in drug abuse research for 13 years and has made important contributions to elucidating the effects of psychostimulants on dopamine (DA) transporter (DAT) and vesicular monoamine transporter-2 (\/MAT-2) regulation and function, especially as related to the neurotoxic effects of the amphetamines. The applicant is a current K02 recipient, and this has permitted the applicant to dramatically decrease her institutional responsibilities and devote 75% of her time to research and professional development as described in her application. Renewal of this award is requested so that the applicant can continue directing research which test the hypotheses that: 1) methamphetamine (METH)-induced DAT complex formation is associated with, and may contribute to, the dopaminergic deficits caused by the stimulant; 2) methylphenidate uniquely affects monoaminergic vesicular function and distribution by a mechanism that includes novel shifts in VMAT-2M-mediated DA transport kinetics; and 3) "latter-stage events" related to intracellular DA management are critical for the persistent dopaminergic deficits caused by METH, and that these events are absent in both adolescent rats and those treated with METH during development. Continued support of this K02 award will not only allow the applicant to expand upon these studies, but also develop expertise in technologies new to her laboratory. In particular, funding of the K02 will facilitate the incorporation of self-administration technology into her laboratory that will permit investigation as to whether transporters are altered in that clinically relevant paradigm. Further, renewal of the K02 will allow the applicant to continue and expand interdisciplinary collaborative efforts with researchers both within and outside of the University of Utah as delineated in the proposal. PUBLIC HEALTH RELEVANCE: Psychostimulant abuse is a significant public health issue. The vesicular monoamine transporter-2 and the dopamine transporter are principal targets of these agents. Accordingly, support for this K02 award will provide support to allow the applicant to study the impact of stimulants such as methamphetamine, cocaine and methylphenidate on transporter function.

描述（由申请人提供）：这是 Annette Fleckenstein 博士的职业发展奖提案。她是犹他大学药理学和毒理学教授。她在药物滥用研究领域活跃了 13 年，在阐明精神兴奋剂对多巴胺 (DA) 转运蛋白 (DAT) 和囊泡单胺转运蛋白 2 (\/MAT-2) 调节和功能的影响方面做出了重要贡献，特别是与安非他明的神经毒性作用相关。申请人目前是 K02 获得者，这使得申请人能够大幅减少其机构职责，并将 75% 的时间投入到申请中所述的研究和专业发展上。请求更新该奖项，以便申请人可以继续指导研究，测试以下假设：1）甲基苯丙胺（METH）诱导的 DAT 复合物形成与兴奋剂引起的多巴胺能缺陷有关，并可能导致该缺陷； 2) 哌醋甲酯独特地影响单胺能囊泡功能和分布，其机制包括 VMAT-2M 介导的 DA 转运动力学的新变化； 3) 与细胞内 DA 管理相关的“后期事件”对于 METH 引起的持续多巴胺能缺陷至关重要，并且这些事件在青春期大鼠和发育过程中接受 METH 治疗的大鼠中都不存在。对 K02 奖项的持续支持不仅使申请人能够扩展这些研究，而且还能为其实验室发展新技术方面的专业知识。特别是，K02 的资助将促进将自我管理技术纳入她的实验室，这将允许调查转运蛋白是否在临床相关范例中发生改变。此外，K02 的更新将使申请人能够继续并扩大与提案中所述的犹他大学内外的研究人员的跨学科合作努力。 公共卫生相关性：精神兴奋剂滥用是一个重大的公共卫生问题。囊泡单胺转运蛋白-2 和多巴胺转运蛋白是这些药物的主要靶标。因此，对该 K02 奖项的支持将为申请人研究甲基苯丙胺、可卡因和哌醋甲酯等兴奋剂对转运蛋白功能的影响提供支持。

项目成果

Iptakalim attenuates self-administration and acquired goal-tracking behavior controlled by nicotine.

• DOI: 10.1016/j.neuropharm.2013.07.019
• 发表时间: 2013-12
• 期刊: Neuropharmacology
• 影响因子: 4.7
• 作者: Charntikov S;Swalve N;Pittenger S;Fink K;Schepers S;Hadlock GC;Fleckenstein AE;Hu G;Li M;Bevins RA
• 通讯作者: Bevins RA