Mu Opioid Receptor in Addiction

描述(申请人提供)：阿片类药物依赖(OD)是一种常见的、慢性的、复发性成瘾，具有实质性的遗传成分。阿片类药物的大部分奖赏效应都是通过Mu阿片受体(Mor)实现的。该开发中心的目标是通过MOR机制研究、小鼠模型研究和人类OD遗传学研究，加深对MOR在OD中的认识。行政核心(AC)将为开发中心提供资金、后勤和组织支持。咨询委员会将发挥三项职能：(1)提供科学领导和评估中心活动；(2)提供行政支持；(3)组织培训和交流活动。咨询委员会将包括项目的负责人(Ferraro博士、Blendy博士、Levenson博士和Berrettini博士)，作为执行委员会。它还将包括一个由三名杰出教授组成的内部咨询委员会，他们在对发展中心至关重要的领域拥有专业知识。这些教授是Charles O‘Brien医学博士、Ted Abel博士和Ellen Unterwald博士。在收到资金通知后，还将根据《框架协议》成立一个外部咨询委员会。执行委员会，包括内部和外部咨询委员会，将指导科学项目和核心，并将评估中心的进展。咨询委员会将负责协调这些工作。此外，咨询委员会将为发展中心的培训举措提供支持，包括推出一门关于阿片类药物的跨学科课程，供宾夕法尼亚大学的研究生和博士后研究员使用。最后，咨询委员会将组织、协助和提供后勤支持，为研究生、博士后研究员和本科生提供外展课程。 公共卫生相关性：海洛因依赖是一个重大的公共卫生问题，有100多万美国成年人受到影响。该项目将提供有关海洛因受体功能的关键信息，海洛因在大脑中与受体结合以产生成瘾效应。这些实验的结果应该为海洛因成瘾治疗的发展提供新的途径，以及提供更少成瘾倾向的慢性疼痛治疗的新机会。

DESCRIPTION (provided by applicant): Opioid dependence (OD) is a common, chronic, relapsing addiction with a substantial genetic component. Central to the neurobiology of OD is the mu opioid receptor (MOR), through which most of the rewarding effects of opioids are mediated. The goal of this developing center is to enhance our understanding of MOR in OD through mechanistic MOR research, mouse model studies and human OD genetic investigations. The Administrative Core (AC) will provide financial, logistical and organizational support to the developing center. The AC will serve three functions: (1) provide scientific leadership and evaluate center activities, (2), offer administrative support and (3) organize training and communication activities. The AC will include the Pis of the projects (Drs. Ferraro, Blendy, Levenson and Berrettini), as an executive committee. It will also include an Internal Advisory Board of three outstanding professors with expertise in areas vital to the developing center. These professors are Charles O'Brien, MD, PhD, Ted Abel, PhD and Ellen Unterwald, PhD. An External Advisory Board will also be constituted, after notification of funding, in accordance with the RFA. The executive committee, with the Internal and External Advisory Boards, will direct the scientific projects and cores, and will evaluate center progress. The AC will co-ordinate these efforts. In addition, the AC will provide support for the training initiatives of the developing center, including the introduction of an interdisciplinary course on opioids, accessible to graduate students and post-doctoral fellows at the University of Pennsylvania. Finally, the AC with organize, facilitate and provide logistic support for a course on OD, to be offered to graduate students, post-doctoral fellows and undergraduate students. PUBLIC HEALTH RELEVANCE: Heroin dependence is a significant public health problem, with more than 1 million US adults affected. This project will provide critical information regarding the function of the receptor to which heroin binds in the brain to produce its addicting effects. The results of these experiments should provide new avenues for development of treatment for heroin addiction, as well as new opportunities to provide chronic pain treatment with less liability to addiction.