NEURAL SUBSTRATES OF PEPTIDE-INDUCED SATIETY

描述（改编自申请人摘要）：长期目标 这项工作的重点是确定神经系统， 影响食物摄入，以从解剖学和 功能上，并最终了解肽和神经元 介导它们的行为参与生理和/或 病理引起的食物摄入变化。 主要研究者（PI）专注于神经系统， 通过缩胆囊素（一种肽）介导食物摄入的抑制 在肠道和大脑中发现。 他发现CCK介导 当某些营养素被放置在食物中时， 小肠 所提出的实验旨在确定 CCK介导的食物摄入量的减少的行为，并在什么类型的 它所起作用的受体 为了实现这些目标，实验解决了 三个具体目标：1）使用药理学和免疫学 方法与限制性药物应用一起识别一般 参与抑制假手术的CCK受体的位置和亚型 通过肠道营养素喂养; 2）利用肠内输注 使肠道神经元脱敏的药物，以评估局部 肠神经支配在小肠抑制摄食中的作用 营养素和外源性CCK;和3）使用免疫组织化学技术， 在解剖学上识别被激活的中枢和外周神经元， 肠刺激和外源性肽。

DESCRIPTION (ADAPTED FROM THE APPLICANT'S ABSTRACT): The long term goals of this work are to identify the neuronal systems through which peptides influence food intake, to characterize these systems both anatomically and functionally, and ultimately to appreciate how peptides and the neurons that mediate their actions participate in physiologically and/or pathologically-induced changes in food intake. The Principal Investigator (PI) has concentrated on neural systems that mediate suppression of food intake by cholecystokinin (CCK), a peptide found in the intestine and in the brain. He has found that CCK mediates reductions of food intake that occur when some nutrients are placed in the small intestine. The proposed experiments are designed to determine where the CCK that mediates reduction of food intake acts and at what type of receptors it acts. To accomplish these ends the experiments address the three following specific aims: 1) use pharmacological and immunological methods together with restricted drug application to identify the general location and subtype of the CCK receptors involved in suppression of sham feeding by intestinal nutrients; 2) utilize intraintestinal infusions of agents that desensitize gut neurons to assess the role of the local intestinal innervation in suppression of food intake by intestinal nutrients and exogenous CCK; and 3) use immuno-histochemical techniques to anatomically identify central and peripheral neurons that are activated by intestinal stimuli and exogenous peptides.