Translational Research on Eating Disorders: Reward Systems

描述(由申请人提供)：进食障碍、厌食症、神经性暴食症和神经性暴食症是严重的精神疾病，影响到相当数量的妇女，并与相当大的发病率和死亡率有关。迫切需要新的方法来理解导致这些疾病持续存在的机制。一些证据表明，这些疾病所特有的进食行为异常在现象学和/或病理生理学水平上与物质使用障碍有相似之处。在目前对成瘾机制的理解和成功用于检查动物进食行为的范例的基础上，拟议的工作将批判性地检查可能导致人类进食障碍发展和持续的机制。这项拟议的工作在两个层面上具有翻译性：第一，从药物成瘾模型到异常进食行为模型，第二，在实验室动物的进食行为模型和人类进食障碍的模型之间。这一应用程序源于一项开发拨款，该拨款在基础和临床研究人员之间建立了合作，这些研究人员在喂养神经科学、成瘾神经科学和饮食障碍方面具有专业知识，重点是饮食障碍。基于在这一合作下开发的范例，当前的应用程序建议检查可能导致人类饮食障碍持续存在的因素，重点是食物奖励的作用，以及多巴胺和阿片系统。这项拟议工作的第一个具体目标是确定和表征饮食失调妇女和适当的对照受试者中食物的激励和奖励作用的行为指数。第二个目的是通过PET研究相同人群中多巴胺释放和受体密度的变化，以及阿片受体密度的变化。公共卫生相关性：拟议的研究将提供关于饮食障碍持续存在的机制以及这些障碍与药物滥用障碍的相似性的新信息。对这些机制的了解将为开发更有效的治疗干预措施提供科学基础。

DESCRIPTION (provided by applicant): The eating disorders Anorexia Nervosa and Bulimia Nervosa are serious psychiatric illnesses that affect a significant number of women and that are associated with substantial morbidity and mortality. New approaches to understanding the mechanisms that contribute to the persistence of these disorders are sorely needed. Several lines of evidence suggest that abnormalities in ingestive behavior characteristic of these disorders bear similarities at a phenomenological and/or pathophysiological level to substance use disorders. Building on current understanding of mechanisms of addiction and on paradigms successfully employed to examine animal eating behavior, the proposed work will critically examine mechanisms that may underlie the development and persistence of human eating disorders. The proposed work is translational at two levels: first, from models of drug addiction to models of abnormal ingestive behavior, and, second, between models of ingestive behavior in laboratory animals and eating disorders in humans. This application grows out of a developmental grant which established collaboration among basic and clinical researchers with expertise in feeding neuroscience, addiction neuroscience, and eating disorders, with a focus on eating disorders. Based on paradigms developed under this collaboration, the current application proposes to examine factors that may contribute to the persistence of human eating disorders, focusing on the role of food reward, and on dopaminergic and opioid systems. The first specific aim of the proposed work is to identify and characterize behavioral indices of the motivating and rewarding effects of food in women with eating disorders and appropriate control subjects. The second aim is to investigate changes in dopamine release and receptor density, and in opioid receptor density via PET in the same populations. PUBLIC HEALTH RELEVANCE: The proposed research will provide new information on mechanisms underlying the persistence of eating disorders and the resemblance of these disorders to disorders of substance abuse. Knowledge of these mechanisms will provide a scientific foundation for the development of more effective treatment interventions.