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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：
7850104
负责人：
HANS-RUDOLF BERTHOUD
金额：
$ 2.99万
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：
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/7850104
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.

摄食行为的开始和维持是由代谢和非代谢共同决定的