CHOLECYSTOKININ IN BRAIN: ITS ROLE IN SATIETY

对脑多肽在代谢调控中作用的认识 而行为很可能会导致治疗上的重大改进 生长、神经和代谢紊乱，例如肥胖。建议数 工作涉及两个多肽家族的作用，即CCK 和阿片肽，在控制摄食行为。大脑CCK，它 是饱腹感的中介物，可能会阻断阿片肽的作用， 刺激进食。然而，角色似乎有所不同，具体取决于 物种。总体目标是利用生化、解剖学和行为学 建立CCK和阿片类药物生理参与的技术 在三个物种中控制取食行为的多肽 他们对中枢和外周给药的不同反应 CCK。实验结果将为1)牵涉到 CCK介导的饱足感和阿片类药物介导的饥饿的特定脑区，2) CCK与阿片肽在脑内特定部位的相互作用 控制取食行为，以及3)物种之间的解剖差异 这可能解释了他们对CCK和阿片类药物的不同反应 多肽。大鼠CCK和阿片肽含量及CCK受体结合 我们将比较大鼠、仓鼠和绵羊大脑的特定区域。 在禁食和肥胖瘦身的条件下。免疫组织化学将会 用来描述和比较CCK胞体和纤维的关系 阿片化摄食相关脑靶体内的多肽胞体和纤维 区域。要确认由以下因素建立的差异反应的重要性 生化和免疫组织化学检测、CCK和阿片肽 将被直接注射到特定的大脑部位，并喂食 我们将衡量他们的反应。这些实验的结果将导致 更全面地了解摄食行为的控制和非常 也可能有更可预测的方法来控制进食障碍。

Understanding of the roles of brain peptides in the control of metabolism and behavior is likely to lead to important improvements in treatments for growth, neurological, and metabolic disorders, e.g. obesity. The proposed work concerns the roles of two families of peptides, cholecystokinin (CCK) and opiate peptides, in the control of feeding behavior. Brain CCK, which is a mediator of satiety, may act to block effects of opiate peptides, which stimulate feeding. It appears, however, that roles vary depending on species. An overall aim is to use biochemical, anatomical and behavioral techniques to establish the physiological involvement of CCK and opiate peptides in the control of feeding behavior in three species chosen for their differential responses to centrally and peripherally administered CCK. Results of experiments will provide evidence for 1) involvement of specific brain areas in CCK-mediated satiety and opioid-mediated hunger, 2) interactions in specific brain sites between CCK and opiate peptides in controlling feeding behavior, and 3) anatomical differences among species which may account for their differential responses to CCK and opiate peptides. CCK and opiate peptide content and CCK receptor binding in specific loci of the brain of rats, hamsters, and sheep will be compared under fed-fasted and obese-lean conditions. Immunohistochemistry will be used to describe and compare the relationship of CCK cell bodies and fibers to opiate peptide cell bodies and fibers in feeding-associated brain target areas. To confirm the importance of differential responses established by the biochemical and immunohistochemical measures, CCK and opiate peptides will be administered directly into specific brain sites, and feeding responses will be measured. The results of these experiments will lead to a more complete understanding of the controls of feeding behavior and very likely also to more predictable means of controlling feeding disorders.