Neuroimaging of Drug Craving in Cocaine Dependence

描述：（申请人提供） 这是一份以病人为导向的研究职业指导申请表 发展奖（K23），题为“药物引发的渴望的神经成像， 依赖性。“候选人之前的培训是在临床 精神病学，临床精神病学研究和成瘾精神病学，包括 熟悉神经成像技术。通过这项提案，候选人 寻求获得以下方面的高级培训：（1）功能性磁共振成像 （2）认知神经科学方法论 与成瘾研究有关，（3）神经内分泌学和 成瘾精神病学，和（4）临床研究设计和分析，包括 先进的统计分析相关的功能磁共振成像数据，功率分析，道德和 负责任地开展临床研究。 旨在补充这一培训计划的研究项目将 研究通过使用 可卡因注射，功能磁共振成像，神经内分泌学和实验心理学。 对候选人和一个扩大的调查小组的研究表明， 在药物渴求期间活跃的大脑区域之间的分离 vs.药物诱发的欣快感具体来说，他们发现， 和杏仁核在功能磁共振成像信号中显示出与渴望相关的明显变化 对可卡因的反应。拟议的项目将扩大和阐述 以前的发现。具体目标1将复制和完善的调查结果， 在一个更大的可卡因依赖受试者队列中进行的初步研究。它将 描述不同剂量的fMRI渴求反应，并比较 两个预先选择的高与低渴望组匹配的欣快作用。 在这个具体目标中，还评估了 神经相关的渴望和情绪，压力和主要的神经内分泌 应激反应调节剂促肾上腺皮质激素和皮质醇。了解可卡因 产生其行为效应进一步需要研究的认知 craving的背景。具体目标2相应地将探讨预期 条件效应即，与渴望相关的电路是否会 不同的是，在受试者知道更多的可卡因是 可用与额外消费药物的情况 不可能的最后，具体目标3将确定 研究结果关于可卡因渴望通过低剂量吗啡输注， 健康对照受试者与可卡因依赖受试者。 该计划将为申请人提供所需的整合培训 神经成像技术和行为药理学的范例， 成瘾的病理生理学研究。多学科指导 该计划将促进候选人的发展，成为一个独立的 药物滥用神经精神病学调查员研究计划将允许 他来确定特定的皮层下结构的作用， 可卡因引发的渴望，从而提高对机制的理解 潜在的可卡因依赖此外，它可能为 开发针对这种疾病的新治疗策略

DESCRIPTION: (Provided by Applicant) This is an application for a Mentored Patient-Oriented Research Career Development Award (K23) entitled "Neuroimaging of Drug-Primed Craving in Cocaine Dependence." The candidate's previous training was in clinical psychiatry, clinical psychiatric research and addiction psychiatry and includes familiarity with neuroimaging technology. Through this proposal, the candidate seeks to gain advanced training in: (1) functional magnetic resonance imaging (fMRI) physics and analytic techniques, (2) cognitive neuroscience methodology relevant to addiction research, (3) the interface of neuroendocrinology and addiction psychiatry, and (4) clinical research design and analysis, including advanced statistical analysis relevant to fMRI data, power analyses, ethics and responsible conduct of clinical research. The research project that is designed to complement this training program will investigate the functional networks subserving craving through the use of cocaine infusions, fMRI, neuroendocrinology and experimental psychology. Studies involving the candidate and an extended group of investigators suggest dissociation between those brain regions that are active during drug craving vs. drug-induced euphoria. Specifically, they find that the nucleus accumbens and amygdala show distinct changes in fMRI signal that correlate with craving in response to cocaine. The proposed project will expand and elaborate upon the previous findings. Specific Aim 1 will replicate and refine the findings from the initial study in a larger cohort of cocaine dependent subjects. It will characterize the fMRI craving response across various doses and compare between two pre-selected groups of high vs. low cravers matched for euphorogenesis. Embedded in this Specific Aim is also an assessment of the association between neural correlates of craving and mood, stress and the main neuroendocrine modulators of stress response, ACTH and cortisol. Understanding how cocaine produces its behavioral effect further necessitates study of the cognitive context of craving. Specific Aim 2 accordingly will explore expectancy condition effects i.e., whether circuitry associated with craving respond differently in a situation in which the subject knows that more cocaine is available vs. a situation where additional consumption of the drug is impossible. Finally, Specific Aim 3 will determine the specificity of the findings concerning cocaine craving through low dose morphine infusions in healthy comparison subjects vs. cocaine dependent subjects. This program will provide the applicant with needed training on the integration of neuroimaging technologies and behavioral pharmacology paradigms for the study of the pathophysiology of addictions. The multidisciplinary mentorship plan will foster the candidate's development toward becoming an independent investigator in substance abuse neuropsychiatry. The research plan will allow him to determine the roles of specific subcortical structures that mediate cocaine-primed craving, thus improving the understanding of the mechanisms underlying cocaine dependence. Furthermore, it may point the way for the development of novel therapeutic strategies for this disease