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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS020000-07
Application #
3400161
Study Section
Biopsychology Study Section (BPO)
Project Start
1983-01-01
Project End
1989-08-31
Budget Start
1988-07-01
Budget End
1989-08-31
Support Year
7
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Della-Fera, M A; Baile, C A; Coleman, B D et al. (1990) Central nervous system injection of dynorphin-(1-13) overrides gastric satiety factors in sheep. Am J Physiol 258:R946-50
Della-Fera, M A; Coleman, B D; Baile, C A (1990) CNS injection of CCK in rats: effects on real and sham feeding and gastric emptying. Am J Physiol 258:R1165-9
Della-Fera, M A; Coleman, B D; Doubek, C A et al. (1989) Cholecystokinin concentration in specific brain areas of rats fed during the light or dark phase of the circadian cycle. Physiol Behav 45:801-7
Miner, J L; Della-Fera, M A; Paterson, J A et al. (1989) Lateral cerebroventricular injection of neuropeptide Y stimulates feeding in sheep. Am J Physiol 257:R383-7
Baile, C A; McLaughlin, C L; Buonomo, F C et al. (1987) Opioid peptides and the control of feeding in sheep. Fed Proc 46:173-7
Marson, L; Lauterio, T J; Della-Fera, M A et al. (1987) Immunohistochemical distribution of cholecystokinin, dynorphin A and Met-enkephalin neurons in sheep hypothalamus. Neurosci Lett 81:35-40
Miceli, M O; van der Kooy, D; Post, C A et al. (1987) Differential distributions of cholecystokinin in hamster and rat forebrain. Brain Res 402:318-30
McLaughlin, C L; Stern, J S; Baile, C A (1987) Weight gain and food intake in corticotropin releasing factor immunized Zucker rats. Physiol Behav 41:171-8
Baile, C A; McLaughlin, C L (1987) Mechanisms controlling feed intake in ruminants: a review. J Anim Sci 64:915-22
Scallet, A C; McLaughlin, C L; Della-Fera, M A et al. (1986) Clonidine has a bidirectional effect on operant responding for food. Physiol Behav 38:295-7

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