Non-Homeostatic Neural Controls of Food Intake

食物摄入的非稳态神经控制

• 批准号: 7185042
• 负责人: HANS-RUDOLF BERTHOUD
• 金额: $ 29.26万
• 依托单位: LSU PENNINGTON BIOMEDICAL RESEARCH CTR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-15 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7185042
• 关键词: Ablation; Acute; Affect; Agonist; Amygdaloid structure; Anatomy; Appetitive Behavior; Area; Behavioral; Body Composition; Body Weight; Body measure procedure; Brain Stem; Cerebral Ventricles; Chemicals; Chronic; Cognitive; Communication; Corpus striatum structure; Cues; Desire for food; Development; Diet; Eating; Emotional; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Environment; Expectancy; Exposure to; FOS gene; Fatty acid glycerol esters; Feeding behaviors; Food; Globus Pallidus; Human; Hypothalamic structure; Immunohistochemistry; In Situ Hybridization; Incentives; Ingestion; Injection of therapeutic agent; Intake; Ipsilateral; Knock-out; Lateral; Learning; Lesion; Life Style; Limbic System; Localized; Macronutrients Nutrition; Maintenance; Measures; Melanocortin 4 Receptor; Metabolic; Middle Hypothalamus; Modeling; Molecular; Mus; Muscimol; Neurons; Neuropeptides; Nucleus Accumbens; Obesity; Opioid Receptor; POMC gene; Pathway interactions; Pattern; Peptide Receptor; Peptides; Phenotype; Play; Prefrontal Cortex; Pro-Opiomelanocortin; Process; Proxy; Rattus; Receptor Signaling; Regulation; Rewards; Role; Series; Signal Transduction; Site; Social Environment; Stimulus; Structure; Structure of nucleus infundibularis hypothalami; System; Taste Perception; Testing; Therapeutic; Thinking; Transgenic Mice; Ventral Striatum; Work; base; beta-funaltrexamine; cohort; emotional factor; energy balance; feeding; hedonic; hypocretin; insight; loss of function; mRNA Expression; melanocortin receptor; mouse model; neurochemistry; neuroregulation; prevent; psychologic; receptor; relating to nervous system; research study; response; tool

DESCRIPTION (provided by applicant): The initiation and maintenance of ingestive behavior is co-determined by metabolic and non-metabolic factors. Among the latter, environmental cues as well as reward, cognitive and emotional factors play an important role, particularly in human food intake in the modern world. These non-homeostatic factors are processed mainly in cortico-limbic structures such as the prefrontal cortex, amygdala, and ventral striatum. An important issue is to understand how and where metabolic and non-metabolic factors are integrated to drive food intake. The proposed work focuses on one aspect of this issue by examining the anatomical, neurochemical, and functional relationship between the ventral striatum and the hypothalamic peptidergic circuits implicated in the homeostatic regulation of energy balance. In Aim 1, we identify hypothalamic targets of ventral striatal projections involved in the robust intake of specific foods induced by chemical manipulations within the nucleus accumbens or ventral pallidum, using Fos expression, neuronal tracing, immunohistochemistry, and in situ hybridization. In Aim 2 we hypothesize that chemical manipulations in the nucleus accumbens stimulate further food intake and override normal homeostatic controls in fully satiated rats by acting on orexigenic and/or anorexigenic hypothalamic signaling systems. We test this by using pharmacological experiments with selective antagonists and agonists against "feeding" peptide receptors, anatomically localized immunotoxic lesions, and murine knockout models. In Aim 3 we hypothesize that ventral striatum D hypothalamus projections play an important role in the acute hyperphagic response to palatable foods and in the development of obesity with chronic exposure to palatable diets. To this end, we use two different chronic lesion models that interrupt specific components of ventral striatal-hypothalamic circuitry, and measure both "liking" and "wanting" aspects of food intake as well as adiposity and body weight. The results will be important for (1) gaining detailed anatomical and neurochemical insight into the relationship between reward and homeostatic neural systems, (2) the development of a conceptual framework of how the different psychological processes involved in food reward are neurologically organized, and (3) the development of pharmacological and behavioral therapeutic tools to counteract "common" obesity in a world of plenty

描述（由申请方提供）：摄食行为的启动和维持由代谢和非代谢因素共同决定。在后者中，环境线索以及奖励，认知和情感因素起着重要作用，特别是在现代世界的人类食物摄入中。这些非稳态因素主要在皮质边缘结构中处理，如前额皮质、杏仁核和腹侧纹状体。一个重要的问题是了解代谢和非代谢因素是如何以及在哪里整合来驱动食物摄入的。拟议的工作集中在这个问题的一个方面，通过检查腹侧纹状体和下丘脑肽能电路之间的解剖，神经化学和功能关系，涉及能量平衡的稳态调节。 在目的1中，我们确定下丘脑腹侧纹状体投射的目标参与了强烈的摄入量的特定食物的化学操纵内的核内的丘脑腹侧苍白球，使用Fos表达，神经元示踪，免疫组织化学和原位杂交。在目标2中，我们假设，在核的化学操作刺激进一步的食物摄入和推翻正常的稳态控制完全饱足大鼠通过作用于orexigenic和/或orexigenic下丘脑信号系统。我们通过使用选择性拮抗剂和激动剂对“喂养”肽受体，解剖学定位的免疫毒性病变，和小鼠基因敲除模型的药理学实验来测试这一点。在目标3中，我们假设腹侧纹状体D下丘脑的预测发挥了重要作用，在急性hyperphagic反应可口的食物和肥胖症的发展与慢性暴露于可口的饮食。为此，我们使用两种不同的慢性病变模型，中断腹侧纹状体-下丘脑回路的特定组成部分，并测量食物摄入的“喜欢”和“想要”方面以及肥胖和体重。这些结果将对以下方面具有重要意义：（1）获得详细的解剖学和神经化学知识，以了解奖赏和自我平衡神经系统之间的关系;（2）发展一个概念框架，说明食物奖赏中涉及的不同心理过程是如何在神经学上组织起来的;以及（3）发展药理学和行为治疗工具，以对抗物质丰富的世界中的“常见”肥胖