Nucleus accumbens opioid-dependent mechanisms of binge eating

伏隔核阿片类药物依赖性暴食机制

基本信息

批准号：
8242432
负责人：
SALEEM M NICOLA
金额：
$ 24.98万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-01-15 至 2013-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8242432
关键词：
Adult Affect American Animal Model Animals Appetitive Behavior Attenuated Behavior Behavior Control Binge Eating Binge eating disorder Brain Brain region Bulimia Consumption Control Animal Coupled Cues Dependence Development Disease Dopamine Dopamine Receptor Drug Addiction Fatty acid glycerol esters Food Goals Injection of therapeutic agent Intervention Life Ligands Liquid substance Medical Mental Depression Modeling Naltrexone Neurons Nucleus Accumbens Obesity Opioid Opioid Peptide Opioid Receptor Pattern Pharmacologic Substance Population Public Health Rattus Receptor Activation Research Rewards Rodent Sucrose Techniques Testing Time Up-Regulation addiction awake dopamine transporter endogenous opioids feeding food consumption medical complication mu opioid receptors neural circuit neurochemistry neuromechanism neurotransmission novel receptor research study response sugar

项目摘要

DESCRIPTION (provided by applicant): Bulimia nervosa and binge eating disorder ("binge eating disorders") are serious public health problems, in part because people with these disorders tend also to suffer other medical complications, such as obesity and depression. Recently, animal models of binge eating have been developed, in which rats are provided intermittent access to sweet and/or high fat food. As consumption of this food escalates over several weeks of access, neurochemical changes in the nucleus accumbens (NAc) are observed, including increases in expression of opioid receptors. Pilot experiments show that injection of a broad-spectrum opioid receptor antagonist into the NAc has more pronounced effects on sweet/fat liquid consumption in binge eating than in control rats. These results suggest that binge eating could be due, at least in part, to upregulation of opioidergic neurotransmission in the NAc. To test this hypothesis, we will first determine which of three opioid receptors (mu, delta and kappa) in the NAc contributes to consumption of palatable liquid, and whether these contributions are different in binge eating and control rats. We will also determine whether these contributions are specific to the core or shell regions of the NAc. In addition, we will determine whether encoding of palatability by NAc neurons differs from controls in binge eating rats. Finally, we will test the hypotheses that endogenous opioids contribute to palatability encoding by NAc neurons, and that this contribution is different in binge eating vs control animals. Our goal is to elucidate the neural mechanisms that underlie binge eating, so that pharmaceutical treatments for binge eating disorders can be developed that specifically target these mechanisms. Because the same neural circuits are involved in drug addiction, our studies will also contribute towards understanding the neural mechanisms of addiction, and of reward-seeking behavior in general. PUBLIC HEALTH RELEVANCE: Approximately 5% of the American population suffers, during at least part of adult life, from binge eating disorder or bulimia nervosa ("binge eating disorders"); these are serious public health problems because of the associated medical complications such as depression and obesity. The research proposed here will use an animal model of binge eating to help us understand how brain circuits that are critical for reward-seeking and feeding control these behaviors, and how circuit activity changes to produce binge eating. Identifying specific neural mechanisms responsible for binge eating will potentially stimulate the development of pharmacological interventions that specifically target these mechanisms to treat binge eating disorders.

描述（由申请人提供）：神经性贪食症和暴食症（“暴食症”）是严重的公共卫生问题，部分原因是患有这些疾病的人还往往患有其他并发症，例如肥胖和抑郁症。最近，已经开发出暴食的动物模型，其中向大鼠提供间歇性的甜食和/或高脂肪食物。随着几周内这种食物的消耗量不断增加，伏隔核（NAc）中的神经化学变化被观察到，包括阿片受体表达的增加。初步实验表明，与对照大鼠相比，向 NAc 中注射广谱阿片受体拮抗剂对暴食大鼠的甜/脂肪液体消耗有更显着的影响。这些结果表明，暴食可能至少部分是由于 NAc 中阿片类神经传递的上调所致。为了检验这一假设，我们将首先确定 NAc 中的三种阿片受体（mu、delta 和 kappa）中的哪一种有助于美味液体的消耗，以及这些作用在暴食大鼠和对照大鼠中是否有所不同。我们还将确定这些贡献是否特定于 NAc 的核心或外壳区域。此外，我们将确定 NAc 神经元对适口性的编码是否与暴食大鼠的对照不同。最后，我们将测试以下假设：内源性阿片类药物有助于 NAc 神经元编码的适口性，并且这种贡献在暴食动物与对照动物中是不同的。我们的目标是阐明暴食背后的神经机制，以便开发出专门针对这些机制的暴食症药物治疗方法。由于药物成瘾涉及相同的神经回路，因此我们的研究也将有助于理解成瘾和一般寻求奖励行为的神经机制。公共卫生相关性：大约 5% 的美国人至少在成年后的一部分时间里患有暴食症或神经性贪食症（“暴食症”）；由于抑郁症和肥胖症等相关的医疗并发症，这些都是严重的公共卫生问题。这里提出的研究将使用暴食动物模型来帮助我们了解对于寻求奖励和进食至关重要的大脑回路如何控制这些行为，以及回路活动如何变化以产生暴食。识别导致暴食的特定神经机制将有可能刺激专门针对这些机制来治疗暴食症的药物干预措施的开发。