Mu Opioid Receptor in Addiction

描述（由申请人提供）： 阿片类药物依赖（OD）是一种常见的、慢性的、复发性的成瘾，具有相当大的遗传成分。OD的神经生物学的中心是μ阿片受体（莫尔），阿片类药物的大多数奖赏效应通过该受体介导。这个发展中的中心的目标是通过莫尔机制研究、小鼠模型研究和人类OD遗传学研究来增强我们对OD中莫尔的理解。行政核心（AC）将为开发中心提供财务，后勤和组织支持。咨询委员会将履行三项职能：（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。AC将包括项目的PI（Ferraro、Blendy、Levenson和Berrettini博士），作为执行委员会。它还将包括一个由三位杰出教授组成的内部咨询委员会，这些教授在发展中心至关重要的领域具有专业知识。这些教授是查尔斯奥布莱恩，医学博士，博士，特德阿贝尔，博士和埃伦Unterwald，博士。在收到供资通知后，还将根据外地住房准备金设立一个外部咨询委员会。执行委员会与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。AC将协调这些努力。此外，AC将为发展中中心的培训计划提供支持，包括引入关于阿片类药物的跨学科课程，可供宾夕法尼亚大学的研究生和博士后研究员使用。最后，咨询委员会负责组织、促进和提供后勤支助，为研究生、博士后研究员和本科生开设一门关于OD的课程。 公共卫生相关性： 海洛因依赖是一个严重的公共卫生问题，超过100万美国成年人受到影响。该项目将提供有关海洛因在大脑中结合产生成瘾作用的受体功能的关键信息。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.