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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS020000-04
Application #
3400159
Study Section
Biopsychology Study Section (BPO)
Project Start
1983-01-01
Project End
1987-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
4
Fiscal Year
1985
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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