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Non-Homeostatic Neural Controls of Food Intake

食物摄入的非稳态神经控制

基本信息

批准号：
7995778
负责人：
HANS-RUDOLF BERTHOUD
金额：
$ 2.24万
依托单位：
LSU PENNINGTON BIOMEDICAL RESEARCH CTR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-12-14 至 2011-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7995778
关键词：
Ablation Acute Affect Agonist Amygdaloid structure Anatomy Area Behavioral Body Composition Body Weight 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 Macronutrients Nutrition Maintenance Measures Melanocortin 4 Receptor Metabolic Middle Hypothalamus Modeling Molecular Mus Muscimol Neurons Neuropeptides Nucleus Accumbens Obesity Opioid Receptor Pathway interactions Pattern Peptide Receptor Peptides Phenotype Play Prefrontal Cortex 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 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

项目摘要

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.

摄食行为的启动和维持是由代谢和非代谢共同决定的。因素在后者中，环境线索以及奖励、认知和情感因素起着重要作用。重要的作用，特别是在现代世界的人类食物摄入量。这些非稳态因素是主要在皮质边缘结构如前额叶皮质、杏仁核和腹侧纹状体中处理。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的，驱动食物摄入。拟议的工作集中在这个问题的一个方面，通过检查解剖，腹侧纹状体和下丘脑肽能神经化学和功能之间的关系与能量平衡的稳态调节有关的回路。在目的1中，我们确定了腹侧纹状体投射的下丘脑靶点，这些靶点参与了大量的特定的食物诱导的化学操作内的核腹侧苍白球，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，我们假设丘脑核中的化学操作刺激了进一步的食物摄入，通过作用于食欲和/或食欲下丘脑信号传导在完全饱足大鼠中的稳态控制系统.我们通过使用选择性拮抗剂和激动剂的药理学实验来测试这一点， “进食”肽受体、解剖学定位的免疫毒性损伤和鼠敲除模型。在目的3我们假设腹侧纹状体D下丘脑投射在急性脑梗死中起重要作用，对可口食物的贪食反应以及长期接触可口的饮食为此，我们使用两种不同的慢性病变模型，腹侧纹状体-下丘脑回路，并测量食物摄入的“喜欢”和“想要”方面肥胖症和体重。结果将是重要的（1）获得详细的解剖和（2）奖励和自我平衡神经系统之间的关系的神经化学见解，发展一个概念框架，说明不同的心理过程如何参与食物奖励是神经组织的，（3）药理学和行为治疗的发展在一个物质丰富的世界里对抗“常见”肥胖的工具。