Role of the Endocannabinoid System in Compulsive Eating

内源性大麻素系统在强迫性饮食中的作用

• 批准号: 8111707
• 负责人: Pietro Cottone
• 金额: $ 39.46万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-15 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8111707
• 关键词: 2-arachidonylglycerol; Abstinence; Affect; Affective; Amygdaloid structure; Animal Model; Anxiety; Anxiety Disorders; Behavior; Behavioral; Binge Eating; Brain; Brain region; CNR1 gene; Cell Nucleus; Chronic; Depressive disorder; Development; Diet; Drug Addiction; Eating; Eating Disorders; Endocannabinoids; Enzymes; Epidemic; Etiology; Feedback; Food; Gene Expression; Hyperphagia; Intake; Intervention; Lead; Link; Lipids; Literature; Measures; Metabolic; Molecular; Mood Disorders; Negative Reinforcements; Neurobiology; Neurotransmitters; Obesity; Play; Rattus; Recruitment Activity; Reinforcement Schedule; Relapse; Research; Rewards; Risk Factors; Role; Self Stimulation; Signal Transduction; Stimulus; Swimming; System; Techniques; Testing; Time; Tissues; Western Blotting; Withdrawal; activity-based protein profiling; anandamide; base; biological adaptation to stress; depressive symptoms; drug of abuse; drug relapse; feeding; hedonic; liquid chromatography mass spectrometry; negative emotional state; neuroadaptation; novel; preference; public health relevance; receptor; receptor density; research study; response

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. PUBLIC HEALTH RELEVANCE: These experiments will provide critical information about the brain changes that accompany compulsive eating of palatable food and their relevance in the development of comorbid anxiety and mood disorders. Such information is important for the development of more efficacious treatments for eating disorders and obesity.

描述（由申请人提供）：流行性饮食失调和肥胖症，例如吸毒，可以概念化为慢性复发条件，持续节制（例如，节食以避免“禁止”食物）和复发（不可察觉的食物饮食），尽管持续了负面影响）。可口食品和节食的可用性增加被认为是危险因素。饮食失调和肥胖症经常与焦虑和情绪障碍合并症，但是两种病理状况之间的神经生物学联系很少了解。申请人最近提出了对强迫性饮食和合并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（类似于对药物的过度摄入和复发）产生的。在这种情况下，有越来越多的证据表明内源性大麻素系统在享乐式喂养中起作用，人们认为它的激活是反对焦虑的负反馈系统的一部分。我们的初步证据表明，在戒酒期间，在戒酒期间招募了扩展杏仁核中的内源性大麻素系统。因此，这里的一般假设是，杏仁核内源性大麻素系统中的神经适应通过负面增强机制可持续可口的食物摄入量，并反对可口食品戒断的负面情感后果。 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杏仁核有助于强迫饮食的负强化机制。 公共卫生相关性：这些实验将提供有关强迫食用可口食品的大脑变化的关键信息及其在合并症焦虑和情绪障碍发展中的相关性。此类信息对于开发更有效的饮食失调和肥胖症很重要。