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: 8145565
• 负责人: Jesus Mena
• 金额: $ 2.62万
• 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 2012-08-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8145565
• 关键词: Address; Agonist; Animals; Appetitive Behavior; Area; Arousal; Attention deficit hyperactivity disorder; Behavior; Behavioral; Behavioral Mechanisms; Body Weight; Cannulations; Cognitive; Disease; Eating; Employee Strikes; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Epidemic; Feeding behaviors; Food; Food deprivation (experimental); Gene Expression; Goals; Heart Diseases; Hyperactive behavior; Hypothalamic structure; Infusion procedures; Knowledge; Laboratories; Lateral; Lead; Maps; Medial; Mediating; Mind-Body Method; Motivation; Motor; Neurons; Neuropharmacology; Non-Insulin-Dependent Diabetes Mellitus; Nucleus Accumbens; Obesity; Opioid; Opioid Receptor; Peptides; Phenotype; Prefrontal Cortex; Process; Reporting; Risk; Role; Sample Size; Schizophrenia; Signal Transduction; Specificity; Stroke; Structure; System; Testing; Work; design; executive function; feeding; frontal lobe; hedonic; insight; mu opioid receptors; novel; public health relevance; research study; 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.

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。