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更多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。甲基苯丙胺滥用研究中心（MARC）将在分子，神经化学，解剖学，行为和临床水平上表征MA给药和戒断的影响，以确定MA滥用者康复的障碍。在临床前和临床研究中使用常见的方法解决的主要主题包括MA的神经适应性，MA相关行为的神经解剖学，应激反应和冲动。人类和动物的协议相互告知这些主题，形成了双向转化研究的基础。该中心的行政核心促进MARC调查人员之间的互动，生物统计学核心分析内部和跨组件的关联和相关性。动物中心培育和维护遗传选择的品系和其他品系，并将其提供给MARC调查人员。教育中心协调医学博士的研究培训。和博士博士前和博士后研究员，并组织和传播来自MARC研究人员的临床和临床前信息到中心和受MA生产和滥用影响的俄勒冈州农村地区。科学组件5将乙酰胆碱释放与MA的主动和被动给药相关联，并提供与寻求在其他组件中使用的MA相关的神经解剖学和分子信号传导数据。科学组件6，检查遗传影响，以及行为和神经化学相关性（与组件5合作）在小鼠中选择MA诱导的神经适应和MA自我管理的差异。从这项临床前工作中提名遗传候选者可以为临床组分7中的治疗策略提供信息，并且可以在临床组分的患者中寻找特定的遗传关联。科学组件7评估了住院患者摄入时的症状严重程度与治疗失败之间的关系，测试了β-受体和胆碱能药物，并进行了压力源反应性的人体实验室评估。组成部分8，试点项目，提供了一种手段，以支持发展多个新的方向，在研究滥用MA。因此，MARC的主题使用创新的多学科方法解决临床相关问题。

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.