Methamphetamine Abuse Research Center

描述(由申请人提供)： 俄勒冈州是少数几个招募没有较大可卡因滥用史的甲基苯丙胺(MA)滥用者进行临床研究的州之一。甲基安非他明滥用研究中心(MARC)将在分子、神经化学、解剖学、行为和临床水平上表征MA滥用和戒断的影响，以确定MA滥用者康复的障碍。临床前和临床研究的主要主题包括对MA的神经适应、MA相关行为的神经解剖学、应激源响应性和冲动性。人类和动物的协议在这些主题上相互告知，形成了双向翻译研究的基础。该中心的管理核心促进了MARC调查人员之间的互动，而生物统计核心分析了各组成部分内部和之间的关联和相关性。动物核心培育和维护遗传选择的品系和其他品系，并将它们提供给MARC调查人员。教育中心协调医学博士和博士博士后研究员的研究培训，并组织和传播临床和临床前信息，从MARC研究人员到受MA生产和滥用影响的中心和俄勒冈州农村地区。科学组成部分5将乙酰胆碱的释放与MA的主动和被动给药联系起来，并提供与MA相关的神经解剖学和分子信号数据，以寻求在其他组成部分中使用。科学部分6，检查遗传影响，以及行为和神经化学相关性(与部分5合作)，选择在MA诱导的神经适应和MA自身给药方面存在差异的小鼠。从这项临床前工作中提名候选基因可以为临床部分7的治疗策略提供信息，并且可以从临床部分对患者进行特定的基因关联。科学部分7评估住院患者摄入时的症状严重程度与治疗失败之间的关系，测试(3-受体和胆碱能药物)，并进行应激源响应性的人体实验室评估。试点项目构成部分8提供了一种手段，以支持在研究滥用苯丙醇胺方面发展多个新方向。因此，MARC的主题使用创新的多学科方法解决与临床相关的问题。

DESCRIPTION (provided by applicant): Oregon is one of a few states where methamphetamine (MA) abusers without a greater history of cocaine abuse are recruited for clinical research. The Methamphetamine Abuse Research Center (MARC) will characterize effects of MA administration and withdrawal at molecular, neurochemical, anatomical, behavioral, and clinical levels, to identify obstacles to recovery in MA abusers. Overarching themes addressed in preclinical and clinical research components using common methodologies include neuroadaptation to MA, neuroanatomy of MA-related behaviors, stressor responsivity, and impulsivity. Human and animal protocols inform one another with respect to these themes, forming the basis for bidirectional translational research. The Center's Administrative Core facilitates interactions among MARC investigators, and the Biostatistics Core analyzes associations and correlations within and across components. The Animal Core breeds and maintains genetically selected lines and other strains, and provides them to MARC investigators. The Education Core coordinates the research training of M.D. and Ph.D. pre- and postdoctoral fellows, and organizes and disseminates both clinical and preclinical information from MARC investigators to Centers and Oregon's rural areas that are impacted by MA production and abuse. Scientific Component 5 correlates acetylcholine release with active and passive administration of MA and provides neuroanatomic and molecular signaling data relevant to MA seeking for use in other components. Scientific Component 6, examines genetic influences, and behavioral and neurochemical correlates (in collaboration with Component 5) in mice selected for differences in MA-induced neuroadaptation and MA self-administration. Nomination of genetic candidates from this preclinical work could inform treatment strategies in clinical Component 7, and specific genetic associations can be pursued in patients from clinical components. Scientific Component 7 evaluates the relationship between symptom severity at intake and treatment failure in inpatients, tests (3-receptor and cholinergic medications, and conducts human laboratory evaluations of stressor responsivity. Component 8, the Pilot Projects, provides a means to support the development of multiple new directions in research on MA abuse. Thus, the MARC's themes address clinically relevant issues using innovative multidisciplinary approaches.