Neurobiology of compulsive eating.

强迫性饮食的神经生物学。

基本信息

批准号：
8114548
负责人：
Pietro Cottone
金额：
$ 28.55万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-03-01 至 2016-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8114548
关键词：
Abstinence Acute Affect Affective Amygdaloid structure Anhedonia Animal Model Animals Anxiety Anxiety Disorders Area Behavior Behavioral Binge Eating Brain CRF receptor type 1 Cell Nucleus Chronic Corticotropin-Releasing Hormone DSM-V Dependence Development Diet Drug Addiction Drug usage Eating Eating Disorders Emotional Epidemic Etiology Food Hyperphagia Intervention Link Measures Mediating Mental disorders Molecular Mood Disorders Negative Reinforcements Neurobiology Neurosecretory Systems Obesity Outcome Peptides Peripheral Pharmacological Treatment Radioimmunoassay Rattus Recording of previous events Reinforcement Schedule Relapse Reverse Transcriptase Polymerase Chain Reaction Rewards Rodent Model Role Self Medication Self Stimulation Site Stress Swimming System Testing Withdrawal acute stress base biological adaptation to stress depressive symptoms drug of abuse feeding food consumption lens negative emotional state neuroadaptation novel prevent research study response social stressor

项目摘要

DESCRIPTION (provided by applicant): In the last decades, the epidemic spreading of eating disorders and obesity has raised the question whether certain highly palatable foods may be responsible for the development of a "food dependence". In fact, epidemic eating disorders and obesity, like drug addiction, can be conceptualized as chronic relapsing conditions with alternating periods of abstinence (e.g., dieting to avoid "forbidden" foods) and relapse (uncontrollable eating of palatable foods) that continue despite negative consequences. Eating disorders and obesity very frequently occur comorbidly with anxiety and mood disorders; however the neurobiological link between the two pathological conditions is poorly understood. We have recently proposed a new reliable animal model of palatable food dependence which contributes to the understanding of the etiology of compulsive eating and comorbid anxiety and affective disorders. Compulsive eating may be generated by the recruitment of the extrahypothalamic corticotropin-releasing factor (CRF) brain stress systems and by the emergence of a negative emotional state during abstinence, analogous to withdrawal from abused drugs. Therefore, relying on the general hypothesis that withdrawal generates palatable food overeating as a form of "self-medication," the proposed application will investigate the relationship between compulsive eating and comorbid anxiety and mood disorders. Specifically, the experiments of the proposed Specific Aims use a combined behavioral, pharmacological and molecular approach to elucidate: i) the brain sites important for the pharmacological effects of CRF1 receptor antagonists on the consummatory, emotional and motivational components of compulsive eating; ii) the effects of acute mild stress on food consumption, affectivity, and HPA and CRF responses, in animals with a history of palatable diet-cycling during protracted abstinence; iii) the role of the CRF/CRF1 system in the adaptations of the brain reward system and in the depressive-like behavior induced by the palatable diet alternation. This proposal will elucidate the neurobiological relationship between compulsive eating and comorbid anxiety and mood disorders through the lens of negative reinforcement. A better understanding of the etiology of compulsive eating would help prevent the onset of eating disorders and obesity, and would increase the potential for pharmacological intervention for tens of millions of people. PUBLIC HEALTH RELEVANCE: These experiments will provide critical information about the neurobiological substrates of compulsive eating of palatable food, and their relevance in the development of stress sensitivity and comorbid anxiety and mood disorders. Such information is important for understanding the etiology of eating disorders and obesity and for the development of more efficacious pharmacological treatments.

描述（由申请人提供）：在过去的几十年中，饮食失调和肥胖症的流行引发了这样的问题：某些高度适口的食物是否可能导致“食物依赖”的发展。事实上，流行性饮食失调和肥胖，就像吸毒成瘾一样，可以被概念化为慢性复发性疾病，伴随着禁欲（例如，节食以避免“禁止”食物）和复发（无法控制地吃可口食物）的交替时期，尽管产生了负面后果，但这种情况仍在继续。饮食失调和肥胖经常与焦虑和情绪障碍同时发生。然而，人们对这两种病理状况之间的神经生物学联系知之甚少。我们最近提出了一种新的可靠的可口食物依赖动物模型，这有助于了解强迫性饮食以及共病焦虑和情感障碍的病因。强迫性饮食可能是由于下丘脑外促肾上腺皮质激素释放因子（CRF）脑应激系统的募集以及禁食期间出现的负面情绪状态（类似于戒断滥用药物）而产生的。因此，基于戒断会导致可口食物暴饮暴食作为一种“自我治疗”形式的一般假设，所提出的应用程序将研究强迫性饮食与共病焦虑和情绪障碍之间的关系。具体来说，所提出的具体目标的实验使用行为、药理学和分子相结合的方法来阐明：i）对于CRF1受体拮抗剂对强迫性饮食的完成、情感和动机成分的药理作用重要的大脑部位； ii) 在长期禁食期间有可口饮食循环史的动物中，急性轻度应激对食物消耗、情感以及 HPA 和 CRF 反应的影响； iii) CRF/CRF1 系统在大脑奖励系统的适应以及可口饮食交替引起的抑郁样行为中的作用。该提案将从负强化的角度阐明强迫性饮食与共病焦虑和情绪障碍之间的神经生物学关系。更好地了解强迫性饮食的病因将有助于预防饮食失调和肥胖的发生，并增加对数千万人进行药物干预的可能性。公共健康相关性：这些实验将提供有关强迫性进食美味食物的神经生物学基础及其与压力敏感性和共病焦虑和情绪障碍发展的相关性的关键信息。这些信息对于了解饮食失调和肥胖的病因以及开发更有效的药物治疗非常重要。