Neurobiology of compulsive eating.

描述(申请人提供)：在过去的几十年里，饮食失调和肥胖症的流行蔓延提出了一个问题，即某些非常美味的食物是否可能导致了对食物的依赖。事实上，流行性饮食障碍和肥胖，就像吸毒一样，可以被概念化为慢性复发条件，并交替出现禁欲(例如，为了避免“违禁”食物而节食)和复发(无法控制地吃可口的食物)，尽管有负面后果，但仍在继续。进食障碍和肥胖经常与焦虑和情绪障碍并存；然而，这两种病理疾病之间的神经生物学联系却知之甚少。我们最近提出了一种新的可靠的可口食物依赖动物模型，这有助于理解强迫性进食以及共病焦虑和情感障碍的病因。强迫性进食可能是由于下丘脑外促肾上腺皮质激素释放因子(CRF)大脑应激系统的招募，以及在禁欲期间出现负面情绪状态而产生的，类似于戒断滥用药物。因此，基于这样一个普遍假设，即戒烟会产生美味的食物过量，这是一种“自我用药”的形式，拟议中的应用程序将调查强迫性进食与共病焦虑和情绪障碍之间的关系。具体地说，所提出的特定目标的实验使用行为、药理学和分子方法相结合的方法来阐明：i)CRF1受体拮抗剂对强迫性进食的消耗性、情绪和动机成分的药理作用重要的大脑部位；ii)急性温和应激对长期戒酒期间有可口饮食循环史的动物的食物消耗、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变化引起的抑郁样行为中的作用。这项建议将通过负面强化的镜头来阐明强迫性进食与共病的焦虑和情绪障碍之间的神经生物学关系。更好地了解强迫进食的病因将有助于预防进食障碍和肥胖的发生，并将增加数千万人进行药物干预的可能性。 公共卫生相关性：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的关键信息，以及它们在压力敏感性和共病焦虑和情绪障碍发展中的相关性。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方法非常重要。

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.