Translational Research in Addiction Center

描述（由申请人提供）：甲基苯丙胺滥用和依赖已迅速成为整个美国的一个主要健康问题。然而，对甲基苯丙胺成瘾的神经生物学和治疗的基本和临床理解落后于对其他药物滥用的研究。本提案旨在改善这方面的知识匮乏，并建议在南卡罗来纳医科大学建立一个专注于甲基苯丙胺依赖临床神经生物学的成瘾转化研究中心（TRAC）。在接下来的四年里，我们将建立一个综合的、多学科的团队来探索甲基苯丙胺成瘾的神经通路、认知和行为毒性以及潜在的治疗方法，为提交P50申请做准备。TRAC围绕甲基苯丙胺成瘾转化研究的共同主题进行整合，并将与临床实验室和成像中心合作，采用一种完善的复发动物模型，旨在直接在人类受试者中测试从动物模型中得出的假设。反过来，临床实验室中来自甲基苯丙胺依赖受试者的信息将为动物模型的新方向提供信息和指导。TRAC将在包括细胞、生理和行为在内的许多层面分析中确定介导复发和认知功能的神经生物学适应。我们还将在临床前和临床模型中描述与甲基苯丙胺相关线索相关的消失训练的神经回路以及认知缺陷与药物寻求行为的关系。重要的是，从所有这些项目中获得的神经生物学信息将用于开发合理的药理学治疗，旨在减少复发，改善甲基苯丙胺引起的认知缺陷，并促进灭绝训练。因此，TRAC将允许发展一个多学科的综合研究团队，能够对甲基苯丙胺成瘾和复发的临床神经生物学进行多维分析。作为该中心的一部分，已经建立了一个全面的计划来指导新的教师和学员，并在校园范围内开展成瘾的转化研究。建议在P20供资期间将开发的TRAC基础设施固有的整合和协同作用将为确定新的药理学干预措施提供最佳机会，这些干预措施将有效治疗甲基苯丙胺成瘾并减少这种毁灭性疾病对个人和公共健康的影响。

DESCRIPTION (provided by applicant): 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.