Translational Research in Addiction Center

甲基安非他明滥用和依赖已迅速成为一个主要的健康问题， 美国的然而，神经生物学和治疗的基础和临床理解， 甲基安非他明成瘾的研究落后于对其他滥用药物的研究。这项建议 努力改善这种知识的缺乏，并提出了翻译的发展 成瘾中心（TRAC）专注于甲基苯丙胺的临床神经生物学研究 南卡罗来纳州医科大学的依赖性。在接下来的四年里，我们将开发 综合的多学科团队，以探索神经通路，认知和行为毒性， 甲基苯丙胺成瘾的潜在治疗方法，为提交P50申请做准备。 TRAC是围绕甲基苯丙胺转化研究这一共同主题进行整合的 成瘾，并将采用良好建立的复发动物模型，结合临床 实验室和成像中心的创新合作，旨在直接测试假设得出 从人类受试者的动物模型中。反过来，来自甲基苯丙胺依赖者的信息 临床实验室的受试者将告知和指导动物模型的新方向。TRAC将 确定神经生物学适应介导的复发和认知功能在许多水平， 分析，包括细胞，生理和行为。我们还将在临床前和 临床模型与甲基苯丙胺相关线索相关的灭绝训练的神经回路， 认知缺陷与药物寻求行为的关系。重要的是，神经生物学信息 从所有这些项目中获得的信息将用于开发合理的药物治疗， 减少复发，改善甲基苯丙胺诱导的认知缺陷，并促进灭绝训练。 因此，核心预算资源调拨目标将有助于建立一个多学科的综合研究小组， 对甲基苯丙胺成瘾的临床神经生物学进行多维分析 和复发作为该中心的一部分，已经制定了一项全面的计划，以指导新的教师 和受训人员，并发展校园范围内的成瘾转化研究。 建议将发展的核心预算资源调拨目标基础设施所固有的一体化和协同作用 在P20资助期间，将提供最佳机会， 有效治疗甲基苯丙胺成瘾和减少个人和 这一毁灭性疾病的公共卫生后果。

Methamphetamine abuse and dependence has rapidly become a major health problem throughout the United States. However, basic and clinical understanding of the neurobiology and treatment of methamphetamine addiction has lagged behind research on other drugs of abuse. This proposal endeavors to ameliorate this dearth of knowledge and proposes the development of a Translational Research in Addiction Center (TRAC) focused on the Clinical Neurobiology of Methamphetamine Dependence at the Medical University of South Carolina. Over the next four years, we will develop integrated, multidisciplinary teams to explore the neural pathways, cognitive and behavioral toxicities, and potential treatments for methamphetamine addiction in preparation for the submission of a P50 application. The TRAC is integrated around the common theme of translational research on methamphetamine addiction and will employ a well-established animal model of relapse in conjunction with a clinical laboratory and imaging center in an innovative collaboration designed to directly test hypotheses derived from the animal model in human subjects. In turn, information derived from methamphetamine dependent subjects in the clinical laboratory will inform and guide new directions in the animal models. The TRAC will determine the neurobiological adaptations mediating relapse and cognitive function at many levels of analysis, including cellular, physiological, and behavioral. We will also characterize in both preclinical and clinical models the neural circuitry of extinction training related to methamphetamine-associated cues and the relationship of cognitive deficits to drug-seeking behaviors. Importantly, neurobiological information derived from all of these projects will be used to develop rational pharmacological treatments designed to decrease relapse, improve methamphetamine-induced cognitive deficits, and facilitate extinction training. Thus, the TRAC will allow for the development of a multidisciplinary, integrated research team capable of conducting a multidimensional analysis of the clinical neurobiology underlying methamphetamine addiction and relapse. As part of the Center, a comprehensive plan has been established for mentoring new faculty and trainees and developing campus wide translational research in addiction. It is proposed that the integration and synergy inherent in the TRAC infrastructure that will be developed during the P20 funding period will provide the optimal opportunity for identifying novel pharmacological interventions that will be effective in treating methamphetamine addiction and reducing the individual and public health consequences of this devastating illness.