CHOLECYSTOKININ IN BRAIN: ITS ROLE IN SATIETY

大脑和胃肠道之间的相互作用是 在控制和喂养行为以及GI中都很重要 功能。来自胃肠道转播信息的传入信号 关于食物的类型和数量以及传出的信号 相应地调整运动量和分泌率。两者都有 已知的是CCK和阿片肽 参与中枢神经系统对摄食行为的控制，以及最近 证据也支持他们参与了中枢神经系统对GI的控制 功能。这项提案的总体目标是确定 中枢神经系统CCK和阿片肽是否参与 肠道和大脑之间的相互作用。之前的这一发现 实验室表明，CCK和阿片肽的变化 在进食和禁食的过程中，特定大脑部位的含量会发生变化 老鼠、仓鼠和绵羊。还包括所涉及的多肽和位点 随着多肽的神经解剖学定位，在 这些物种，暗示了行为的可能基础 他们之间的差异。拟议实验的结果 将提供有关大脑部位的信息，这些部位的肽含量 由于胃肠道的营养刺激，会发生变化。 确定传入营养物质来自的GI部位(S) 相关信号会产生，营养物质的输注 局限于上消化道的特定区域(口咽部， 大鼠胃、十二指肠；瘤胃、门静脉/肝、十二指肠 绵羊)。以确定饮食的个别成分是否 (蛋白质，碳水化合物，大鼠脂肪；挥发性脂肪酸，乳酸 绵羊)在产生脑肽含量方面的有效性不同 变化，每个都将被单独注入特定的GI区域。 中枢CCK和阿片肽在胃改变中的作用 功能将通过将它们注入侧方来进行评估 和第四脑室和测量胃(瘤胃、 绵羊的皱胃；大鼠的胃)运动和分泌率。 迷走神经参与传入或传递 传出信息将在大鼠身上通过比较来确定 上述研究结果在迷走神经切断术和假手术中- 去迷走神经的大鼠。老鼠和绵羊在生活中的差异 参与的多肽和脑部位以及GI反应引起的意志 继续帮助建立生理学和 这些物种之间的行为差异。更好 对肠道和大脑相互作用的本质的理解 应该导致治疗病理疾病的新方法 由饮食和胃肠紊乱引起的，并提高了产量 生产动物食物的效率。

Interaction between the brain and gastrointestinal (GI) tract is important in both the control and feeding behavior and GI function. Afferent signals from the GI tract relay information about the type and amount of food eaten and efferent signals modify motility and secretion rate accordingly. Both cholecystokinin (CCK) and opiate peptides are known to be involved in the CNS control of feeding behavior, and recent evidence also supports their involvement in the CNS control of GI functions. The overall aim of this proposal is to determine whether CNS CCK and opiate peptides are involved in the interaction between gut and brain. Previous findings from this laboratory indicated that changes in CCK and opiate peptide content in specific brain sites occurred with feeding and fasting in rats, hamsters and sheep. The peptides and sites involved, as well as the neuroanatomical localization of peptides, varied among these species, suggesting a possible basis for the behavioral differences among them. Results from the proposed experiments will provide information on brain sites in which peptide content changes occur as a result of nutrient stimulation of the GI tract. To determine the GI site(s) from which the afferent nutrient- related signals are generated, infusions of nutrients will be confined to specific regions of the upper GI tract (oropharynx, stomach, duodenum in rats; rumen, portal vein/liver, duodenum in sheep). To determine whether individual components of the diet (protein, carbohydrate, fat in rats; volatile fatty acids, lactate in sheep) vary in effectiveness in producing brain peptide content changes, each will be infused separately into specific GI regions. The role of CNS CCK and opiate peptides in altering gastric functions will be assessed by administering them into the lateral and 4th cerebral ventricles and measuring gastric (rumen, abomasum in sheep; stomach in rats) motility and secretion rates. The involvement of the vagus in relaying either afferent or efferent information will be determined in rats by comparing results from the above studies in vagotomized and sham- vagotomized rats. Differences between rats and sheep in the peptides and brain sites involved and GI responses elicited will continue to help establish bases for the physiological and behavioral differences between these species. Better understanding of the nature of interactions between gut and brain should lead to novel ways of treating pathological conditions resulting from eating and GI disorders and improving production efficiency in food producing animals.