Role of the Endocannabinoid System in Compulsive Eating

描述（由申请人提供）：流行病饮食失调和肥胖，就像药物成瘾一样，可以被定义为慢性复发状态，伴有交替的禁食期（例如，节食以避免“禁止”的食物）和复发期（无法控制的美味食物的进食），尽管有负面后果，但仍在继续。美味食物的增加和节食被认为是危险因素。饮食失调和肥胖经常与焦虑和情绪障碍同时发生，但这两种病理状况之间的神经生物学联系尚不清楚。申请人最近提出了对强迫进食和共病焦虑和情感障碍的病因的新解释：暴饮暴食可能是由与其缺失相关的负面情绪状态（类似于过量摄入药物和复发）产生的。在这种情况下，越来越多的证据表明，内源性大麻素系统在享乐性进食中起着重要作用，它的激活被认为是对抗焦虑的负反馈系统的一部分。我们的初步证据表明，在远离美味食物的过程中，扩展杏仁核中的内源性大麻素系统被招募。因此，这里的一般假设是，扩展杏仁核中的内源性大麻素系统中的神经适应性通过负强化机制维持美味食物的摄入，并反对美味食物戒断的负面情感后果。本应用程序采用综合行为学、药理学和分子方法来研究i)内源性大麻素系统在强迫进食的圆满性和动机成分中的作用，ii)将强迫进食与焦虑和抑郁障碍联系起来的机制以及内源性大麻素系统在此背景下所起的作用。Iii)扩展杏仁核内源性大麻素机制的神经适应性变化，这有助于强迫性进食的负强化机制。

DESCRIPTION (provided by applicant): 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. The increased availability of palatable foods and dieting are believed to be risk factors. Eating disorders and obesity very frequently occur comorbidly with anxiety and mood disorders but the neurobiological link between the two pathological conditions is poorly understood. The applicant has recently proposed a new interpretation of the etiology of compulsive eating and comorbid anxiety and affective disorders: overeating may be generated by the negative emotional state associated with its absence (analogous to excessive intake of drugs and relapse). In this context, there is increasing evidence that the endocannabinoid system plays a role in hedonic feeding and it is believed that its activation is part of a negative feedback system that opposes anxiety. Our preliminary evidences show that the endocannabinoid system in the extended amygdala is recruited during abstinence from palatable food. Therefore, the general hypothesis here is that neuroadaptations in the endocannabinoid system in the extended amygdala sustain palatable food intake via a negative reinforcement mechanism and oppose the negative affective consequences of palatable food withdrawal. The present application uses an integrative behavioral, pharmacological and molecular approach to study i) the role of the endocannabinoid system in the consummatory and motivational components of compulsive eating, ii) the mechanisms which link compulsive eating to anxiety and depressive disorders and the role played by the endocannabinoid system in this context, iii) the neuroadaptational changes in the endocannabinoid machinery in the extended amygdala which contribute to the negative reinforcement mechanisms of compulsive eating.