CHOLECYSTOKININ IN BRAIN: ITS ROLE IN SATIETY

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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.