Hedonic vs. Metabolic Processing by the Nucleus Accumbens

描述(由申请人提供)：PI将确定食物适口性和卡路里含量对食物奖励背后的神经活动的相对贡献。肥胖症的流行在一定程度上是由于无节制地消费高口感、高热量的食物。该区域内的伏隔核和多巴胺信号与食物奖励有关。事实上，它们是构成旨在获得和消费奖励的行为的电路的关键部件。然而，大多数人试图确定食物奖励的生理相关性时，发现适口性和卡路里价值并存。这项研究将确定食物奖励的生理关联是依赖于卡路里的存在，还是取决于味觉刺激的积极享乐方面。这些目标将通过向口腔内注入甜味溶液并改变与它们相关的卡路里负荷来实现。对于目标1和目标2，蔗糖将与非热量甜味剂糖精进行比较。在目标3中，营养物质的胃内输注将与口腔内调味糖精的输注配对。在所有情况下，生理反应都是在伏核进行测量的：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。所有技术都将用于清醒的、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)的Mitchell Roitman博士的实验室进行(对于Aim 3，将在Ivan de Araujo博士的实验室中的耶鲁大学进行)。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。德·阿劳霍博士将教PI进行胃内插管，PI将与伏安法记录相结合。这种新颖的结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，还设立了一个咨询委员会，成员包括Roitman博士、Simon Alford博士(共同导师)和Marina Wolf博士(顾问)。阿尔福德博士和沃尔夫博士在帮助受训者走向独立方面有着出色的记录。此外，他们专门从事体外技术的实验室和资源将可用于收集R01申请的数据，该申请将在本次颁奖期间提交。技术和概念培训将通过教学讲习班、研讨会和会议加以加强。通过UIC的临床和翻译研究中心，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。行业研讨会将提供所提议的新技术方法的最新发展。学术会议将使PI了解技术进步的最新情况，并提供社区的反馈。再加上他之前的培训，这里描述的计划将使PI准备建立一个完全独立的研究程序，使用从分子/细胞到系统/行为的多个层次的分析来确定适应(例如进食)和适应不良(例如吸毒)行为的生物学基础。

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.