Translational Research on Eating Disorders: Reward Systems

描述（由申请人提供）：饮食失调神经性厌食症和神经性贪食症是严重的精神疾病，影响大量女性，并与大量发病率和死亡率相关。迫切需要新的方法来了解导致这些疾病持续存在的机制。多项证据表明，这些疾病的摄入行为异常特征在现象学和/或病理生理学水平上与物质使用障碍具有相似性。基于目前对成瘾机制的理解和成功用于检查动物饮食行为的范式，拟议的工作将批判性地研究可能构成人类饮食失调的发展和持续的机制。拟议的工作在两个层面上进行转化：首先，从毒瘾模型到异常摄入行为模型，其次，在实验动物的摄入行为模型和人类饮食失调模型之间进行转化。该申请源于一项发展资助，该资助在喂养神经科学、成瘾神经科学和饮食失调方面拥有专业知识的基础和临床研究人员之间建立了合作，重点关注饮食失调。基于此次合作开发的范式，当前的申请建议检查可能导致人类饮食失调持续存在的因素，重点关注食物奖励的作用以及多巴胺能和阿片类药物系统。拟议工作的第一个具体目标是确定和表征食物对患有饮食失调的女性和适当的对照受试者的激励和奖励作用的行为指数。第二个目标是通过 PET 研究同一人群中多巴胺释放和受体密度以及阿片受体密度的变化。公共卫生相关性：拟议的研究将提供有关饮食失调持续存在的机制以及这些疾病与药物滥用疾病的相似性的新信息。了解这些机制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.