Hedonic vs. Metabolic Processing by the Nucleus Accumbens

伏隔核的享乐与代谢处理

• 批准号: 8443005
• 负责人: James Edgar McCutcheon
• 金额: $ 12.54万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-01 至 2013-10-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8443005
• 关键词: Advisory Committees; Animals; Artificial Sweeteners; Award; Behavior; Behavioral; Biological; Biological Assay; Brain region; Calories; Cannulations; Chicago; Clinical; Clinical Research; Communities; Conflict (Psychology); Consumption; Coupled; Cues; Data; Data Collection; Development; Diet; Disease; Dopamine; Drug Addiction; Drug Exposure; Educational process of instructing; Educational workshop; Electrodes; Electrophysiology (science); Epidemic; Etiology; Faculty; Feedback; Flavoring; Food; Future; Generations; Glucose; Goals; Health; Human; Illinois; In Vitro; Individual; Industry; Infusion procedures; Laboratories; Learning; Measures; Mentors; Metabolic; Metabolism; Modeling; Molecular Analysis; Monitor; Motivation; Nature; Neurobiology; Neurons; Neurotransmitters; Nucleus Accumbens; Nutrient; Nutritional; Obesity; Pattern; Pharmaceutical Preparations; Phenotype; Physiological; Positioning Attribute; Prevention; Prevention strategy; Process; Rattus; Records; Relative (related person); Research; Resources; Rewards; Role; Saccharin; Scanning; Scientist; Sensory Process; Signal Transduction; Solutions; Stimulus; Sucrose; Sweetening Agents; System; Taste Perception; Techniques; Testing; Time; Training; Universities; Water; Wolves; Work; addiction; awake; base; classical conditioning; conditioning; experience; extracellular; feeding; hedonic; in vivo; novel; public health relevance; relating to nervous system; research study; response; reward circuitry; reward processing; symposium; theories; translational study; treatment strategy

DESCRIPTION (provided by applicant): The PI will determine the relative contributions made by food palatability and caloric content, to neural activity underlying food reward. The obesity epidemic is due, in part, to unchecked consumption of highly palatable, densely caloric foods. The nucleus accumbens and dopamine signaling within this region are associated with food reward. Indeed, they are critical components of the circuitry that underlies behavior directed at obtaining and consuming rewards. However, most attempts to determine physiological correlates of food reward con- found palatability and caloric value. This study will determine whether physiological correlates of food reward are dependent on the presence of calories or the positive hedonic aspects of taste stimuli. The aims will be achieved by delivering intraoral infusions of sweet solutions and varying the caloric load associated with them. For Aims 1 and 2, sucrose will be compared to the non-caloric sweetener saccharin. In Aim 3, intragastric infu- sions of nutrient will be paired with intraoral infusions of flavored saccharin. In all cases, physiological responses are measured in nucleus accumbens: fast-scan cyclic voltammetry will be used to measure phasic fluctuations in dopamine and multi-wire electrophysiology will be used to monitor firing of individual neurons. All techniques are to be employed in awake, behaving rats and are novel technical approaches for the PI. Training will take place at University of Illinois at Chicago (UIC) in the laboratory of Dr. Mitchell Roitman (and for Aim 3, a Yale University in the laboratory of Dr. Ivan de Araujo). Dr. Roitman has extensive experience with the recording techniques as well as the necessary conceptual and theoretical background. Dr. de Araujo will teach the PI to perform intragastric cannulations, which the PI will integrate with voltammetry recordings. This novel combination will set his research path distinct from his mentor and others in the field. Additionally, an Advisory Committee has been established comprising Dr. Roitman, Dr. Simon Alford (co-mentor) and Dr. Marina Wolf (consultant). Drs. Alford and Wolf have excellent track records of advancing trainees to independence. Further- more, their laboratories and resources, specializing in in vitro techniques, will be available for the collection of data for an R01 application to be submitted during this award. Technical and conceptual training will be augmented by didactic workshops, seminars and conferences. Through UIC's Center for Clinical and Translational Studies the PI will gain further appreciation for the nature of clinical disorders of motivation (obesity, drug ad- diction) as well as current treatment and prevention strategies. Industry workshops will provide the very latest developments for the new technical approaches proposed. Academic conferences will keep the PI up-to-date with how technical advances are being employed and provide feedback from the community. Coupled with his previous training, the plan described herein will prepare the PI to establish a fully independent research pro- gram working to determine the biological bases for adaptive (e.g. feeding) and maladaptive (e.g. drug taking) behaviors using multiple levels of analysis - from molecular/cellular to systems/behavioral.

描述（由申请人提供）：PI将确定食物可口性和热量含量对食物奖励相关神经活动的相对贡献。肥胖症的流行部分是由于不加控制地食用高可口、高热量的食物。这个区域内的丘脑核和多巴胺信号与食物奖励有关。事实上，它们是大脑回路的关键组成部分，而大脑回路是获得和消费奖励行为的基础。然而，大多数试图确定食物奖赏的生理相关性的尝试混淆了适口性和热量值。这项研究将确定食物奖励的生理相关性是否取决于卡路里的存在或味觉刺激的积极享乐方面。这些目标将通过口内输注甜味剂溶液和改变与之相关的热量负荷来实现。对于目的1和2，将蔗糖与无热量甜味剂糖精进行比较。在目标3中，营养素的胃内输注将与调味糖精的口内输注配对。在所有情况下，都会测量伏隔核中的生理反应：快速扫描循环伏安法将用于测量多巴胺的相位波动，多线电生理学将用于监测单个神经元的放电。所有技术均用于清醒、行为正常的大鼠，是PI的新技术方法。培训将在伊利诺伊大学芝加哥分校（UIC）Mitchell Roitman博士的实验室进行（Aim 3将在耶鲁大学Ivan de Araujo博士的实验室进行）。Roitman博士在录音技术以及必要的概念和理论背景方面拥有丰富的经验。de Araujo博士将教授PI进行胃内插管，PI将结合伏安法记录。这种新颖的组合将使他的研究道路有别于他的导师和该领域的其他人。此外，还成立了一个咨询委员会，由Roitman博士、Simon阿尔福德博士（共同导师）和Marina Wolf博士（顾问）组成。阿尔福德和沃尔夫博士在推动受训者独立方面有着出色的记录。此外，他们的实验室和资源，专门从事体外技术，将可用于收集数据，为R 01申请提交在此授予。将通过教学讲习班、研讨会和会议加强技术和概念培训。通过UIC的临床和转化研究中心，PI将进一步了解临床动机障碍（肥胖、药物成瘾）的性质以及当前的治疗和预防策略。行业研讨会将提供拟议的新技术方法的最新发展。学术会议将使PI了解最新的技术进步是如何被使用的，并提供来自社区的反馈。结合其先前的培训，本文所述的计划将使PI准备建立一个完全独立的研究计划，该计划将使用从分子/细胞到系统/行为的多层次分析来确定适应性（例如进食）和适应不良（例如吸毒）行为的生物学基础。