Psychostimulant-Induced Craving and Toxicity

描述（由申请人提供）：本申请是由R. Christopher Pierce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，包括：i)将更多的注意力集中在皮尔斯博士的主要研究项目上（由R01 DA15214， R.C. Pierce， PI资助），该项目集中于描述负责恢复可卡因诱导的药物寻求的各种边缘核的神经化学和生化变化；ii)增加这些研究的范围，包括非人类灵长类动物的成像实验，以评估过量摄入可卡因之前、期间和之后中枢神经系统的变化；Iii)学习与磁共振成像和磁共振波谱实验相关的技术和方法细节，这将是完成第二个目标所必需的。目标二和目标三将与博士合作完成。James Rowlett和Itamar Ronen；iv)将Pierce博士的研究项目从相对单一的关注可卡因的行为药理学扩展到包括与其他滥用药物产生的神经毒性相关的问题。具体来说，他将确定MDMA诱导的中枢血清素系统损伤的功能后果，以及可卡因和MDMA之间潜在的毒性相互作用；v)在mdma -可卡因项目的背景下，向Bryan Yamamoto博士和Jean-Jacques Soghomonian博士学习有关神经毒性测量的新技术（即自由基形成、脂质和蛋白质氧化、兴奋性和终端降解的测量）。皮尔斯博士目前将60%的精力用于研究，40%的精力用于教学和行政工作。如果申请获得资助，他将免除25%的非研究职责，85%的时间将用于研究。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，并扩大他与博士的研究合作。Rowlett, Ronen， Yamamoto和Soghomonian，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.