Psychostimulant-Induced Craving and Toxicity

描述(申请人提供)：本申请是由R.Christopher Piells博士提交的K02独立科学家职业发展奖。职业发展计划有五个主要目标，其中包括：i)更多地关注皮尔斯博士的主要研究项目(由R01 DA15214，R.C.Piells，PI资助)，该项目集中描述了导致可卡因诱导的药物寻求恢复的各种边缘核的神经化学和生化变化；Ii)扩大这些研究的范围，将非人类灵长类受试者的成像实验包括在内，以评估在过量吸食可卡因之前、期间和之后中枢神经系统的变化；iii)了解与磁共振成像和磁共振波谱实验有关的技术和方法细节，这将是完成第二个目标所必需的。目标II和目标III将与詹姆斯·罗利特博士和伊塔马尔·罗宁博士合作完成；iv)扩大皮尔斯博士的研究计划，从相对单一的可卡因行为药理学重点扩大到包括与其他滥用药物产生的神经毒性相关的问题。具体地说，他将确定MDMA对中枢5-羟色胺系统造成的损害的功能后果以及可卡因和MDMA之间潜在的毒性相互作用；以及v)在MDMA-可卡因项目的背景下，向Bryan Yamamoto博士和Jean-Jacques Soghomung博士学习与神经毒性措施(即自由基形成、脂质和蛋白质氧化、兴奋性和终端降解的措施)有关的新技术。皮尔斯博士目前将60%的精力投入到研究，40%的精力投入到教学和行政工作中。如果这项申请得到资助，他将从25%的非研究职责中解脱出来，这样他85%的时间将投入到研究中。这一发布时间将使皮尔斯博士能够更多地关注他现有的研究，并扩大他与罗莱特、罗南、山本和索戈霍米尼亚博士的研究合作，这将对他的职业发展产生重大的积极影响。

DESCRIPTION (provided by applicant): This application is a K02 Independent Scientist Career Development Award submitted by R. Christopher Pierce, Ph.D. There are five major goals of the career development plan, which include: i) focusing more attention on Dr. Pierce's primary research program (funded by R01 DA15214, R.C. Pierce, PI), which is concentrated on delineating the neurochemical and biochemical changes in various limbic nuclei responsible for the reinstatement of cocaine-induced drug seeking; ii) increasing the scope of these studies to include imaging experiments in non-human primate subjects in order to evaluate changes in the CNS prior to, during and after periods of excessive cocaine intake; iii) learning the technical and methodological details associated with magnetic resonance imaging and magnetic resonance spectroscopy experiments, which will be required to complete the second goal. Goals ii and iii will be done in collaboration with Drs. James Rowlett and Itamar Ronen; iv) expanding Dr. Pierce's research program from a relatively single-minded focus on the behavioral pharmacology of cocaine to include issues related to the neurotoxicity produced by other drugs of abuse. Specifically, he will determine the functional consequences of MDMA-induced damage of central serotonin systems as well as potential toxic interactions between cocaine and MDMA; and v) learning new techniques from Dr. Bryan Yamamoto and Dr. Jean-Jacques Soghomonian related to measures of neurotoxicity (i.e. measures of free radical formation, lipid and protein oxidation, excitoxicity and terminal degradation) in the context of the MDMA-cocaine project. Dr. Pierce currently devotes 60% effort to research and 40% effort to teaching and administrative duties. If this application is funded, he will be released from 25% of his non-research duties such that 85% of his time will be devoted to research. This release time will allow Dr. Pierce to devote more attention to his existing research and also expand his research collaborations with Drs. Rowlett, Ronen, Yamamoto and Soghomonian, which will have a significant positive impact on his career development.