Mu-opioid systems in the prefrontal cortex: role in appetitive behavior

前额皮质中的 Mu-阿片系统：在食欲行为中的作用

• 批准号: 8008656
• 负责人: Jesus Mena
• 金额: $ 2.91万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-11-01 至 2012-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8008656
• 关键词: Address; Animals; Appetitive Behavior; Area; Attention deficit hyperactivity disorder; Behavior; Behavioral; Body Weight; Cognitive; Disease; Eating; Epidemic; Feeding behaviors; Food deprivation (experimental); Goals; Heart Diseases; Hyperactive behavior; Knowledge; Lead; Medial; Mediating; Mind-Body Method; Motor; Neuropharmacology; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Opioid; Peptides; Prefrontal Cortex; Process; Risk; Role; Schizophrenia; Stroke; System; Work; executive function; hedonic; insight; mu opioid receptors; novel; public health relevance; statistics

DESCRIPTION (provided by applicant): It has been suggested that obesity rates around the world are at epidemic proportions. Relevant to this threat are the sequelae that are associated with obesity, such as increased risk of developing type 2 diabetes, heart disease, and stroke. With these statistics in mind, research into understanding the systems that are involved in regulating body weight and food intake-associated behaviors is critical. There is a notable gap in our understanding of "higher-order" cortical control of basic appetitive behaviors. To address this gap, we propose to explore the medial prefrontal cortex, an area rich in connections to 'downstream' regions that mediate homeostatic and hedonic control of feeding behavior. Particularly germane to this goal are preliminary results from our lab showing that stimulation of mu-opioid receptors in the mPFC augments food intake in both food- deprived and non-deprived animals, and promotes extreme hyperactivity and fragmentation of motor repetoires. Surprisingly, very little is known about the functional role of PFC opioids and very few studies have examined the behavioral effects following local PFC opioid manipulation. Thus, we propose to explore the neuropharmacology and anatomical substrates underlying these effects, and to investigate the precise behavioral constructs underlying our observed effects. PUBLIC HEALTH RELEVANCE: The work outlined in this proposal has the potential to enhance our understanding of how higher-order cognitive factors impinge upon, and perhaps organize and regulate, basic homeostatic mechanisms related to food intake. Hence, this work could lead to novel and exciting insights into the 'top-down' executive control of basic motivational and homeostatic processes. The proposed work may also elucidate important new knowledge regarding peptide control of prefrontal cortical function, which could have profound translational implications for disorders like ADHD and Schizophrenia.

描述（由申请人提供）：已经提出，世界各地的肥胖率处于流行比例。与这种威胁有关的是与肥胖有关的后遗症，例如增加2型糖尿病，心脏病和中风的风险。考虑到这些统计数据，研究了解参与调节体重和食物摄入相关行为的系统至关重要。我们对基本食欲行为的“高阶”皮质控制的理解有一个明显的差距。为了解决这一差距，我们建议探索内侧前额叶皮层，该区域富含与“下游”区域的连接，可介导稳态和享乐主义对喂养行为的控制。该目标的特别是我们实验室的初步结果表明，在MPFC中刺激MU-阿片受体在食物中剥夺和非剥夺动物的食物摄入量增加了食物的摄入量，并促进了重复运动的极端多动症和碎片化。令人惊讶的是，关于PFC阿片类药物的功能作用知之甚少，很少有研究检查了局部PFC阿片类药物操纵后的行为效应。因此，我们建议探索这些作用背后的神经药理学和解剖底物，并研究我们观察到的效果的确切行为构造。 公共卫生相关性：该提案中概述的工作有可能增强我们对高阶认知因素如何影响，甚至组织和调节与食物摄入有关的基本基本稳态机制的理解。因此，这项工作可能会导致对基本动机和稳态过程的“自上而下”执行控制的新颖和令人兴奋的见解。拟议的工作还可以阐明有关前额叶皮质功能的肽控制的重要新知识，这可能对诸如ADHD和精神分裂症等疾病具有深远的翻译意义。