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蔓延提出了一个问题，即某些高度可口的食物是否可能导致“食品依赖”的发展。实际上，流行性饮食障碍和肥胖症（如吸毒，可以概念化为慢性复发疾病，具有持久的节食时期（例如，节食以避免“禁止”的食物）和复发（无法控制的饮食），尽管持续了负面影响）。饮食失调和肥胖症经常与焦虑和情绪障碍合并；但是，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口食品依赖性动物模型，有助于理解强迫性饮食和合并焦虑和情感障碍的病因。强迫性饮食可能是通过募集偏颌骨外皮质激素释放因子（CRF）脑压力系统以及在禁欲期间出现负面情绪状态的出现的，类似于退出滥用药物的情况。因此，依靠一个普遍的假设，即戒断会产生可口的食物，作为“自我药物”的一种形式，拟议的应用将调查强迫性饮食与合并症焦虑与情绪障碍之间的关系。具体而言，所提出的特定目的的实验使用联合行为，药理和分子方法来阐明：i）脑站点对CRF1受体拮抗剂对强制性饮食的完整，情感和动机成分的药理作用很重要； ii）急性轻度应激对食物消耗，情感和HPA和CRF反应的影响，对持久性持续性饮食可口的动物病史； iii）CRF/CRF1系统在大脑奖励系统适应以及可口饮食交替引起的抑郁样行为中的作用。该提议将通过负面增强的角度来阐明强迫性饮食与焦虑症与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防止饮食失调和肥胖症的发作，并增加数千万人的药理干预的潜力。公共卫生相关性：这些实验将提供有关强迫食用食物的神经生物学基材的关键信息，以及它们在压力敏感性和合并焦虑和情绪障碍的发展中的相关性。此类信息对于理解饮食失调和肥胖症的病因以及更有效的药理治疗的发展很重要。