CHOLECYSTOKININ IN BRAIN: ITS ROLE IN SATIETY

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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.