Psychostimulant-Induced Craving and Toxicity

描述（由申请人提供）：本申请是由R。克里斯托弗·皮尔斯博士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R 01 DA 15214，R.C.资助）。Pierce，PI），其集中于描绘负责可卡因诱导的药物寻求的恢复的各种边缘核中的神经化学和生物化学变化; ii）增加这些研究的范围以包括在非人灵长类动物受试者中的成像实验，以评估在过量可卡因摄入期间之前、期间和之后的CNS中的变化; iii）学习与磁共振成像和磁共振光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ii和iii将与James Rowlett博士和Itamar Ronen博士合作完成; iv）将Pierce博士的研究计划从相对专注于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引起的中枢5-羟色胺系统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;和v）向Bryan Yamamoto博士和Jean-Jacques Soghomonian博士学习与神经毒性测量有关的新技术在MDMA-可卡因项目的背景下，对自由基形成、脂质和蛋白质氧化、兴奋毒性和末端降解进行了测量。皮尔斯博士目前致力于60%的努力，研究和40%的努力，教学和行政职责。如果这项申请获得资助，他将从25%的非研究职责中解脱出来，这样他85%的时间将用于研究。这一发布时间将使Pierce博士能够更多地关注他现有的研究，并扩大他与Rowlett，Ronen，Yamamoto和Soghomonian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.