The goal of this project is to elucidate in rats the neuropeptide Y (NPY) circuitry and specific receptor subtypes in the hindbrain that may participate in a larger neural network involved in the control of food intake and the regulation of body weight. Most attention given to NPY's role in food intake has focused on the hypothalamus. The hindbrain has received less attention, even though NPY and its receptors are widespread in hindbrain and NPY-related agonists stimulate feeding when their distribution is restricted to the hindbrain. Experimental aims in this proposal focus on hindbrain NPY and NPY receptors and address several questions: Does NPY activity in hindbrain participate in the physiological control of food intake? This question will be pursued using fourth ventricular administration of specific NPY receptor antagonists. Where is the locus, or loci, where NPY acts to stimulate feeding? Based on preliminary results, we hypothesize a locus exists in the dorsal pons central gray area. This locus, we predict, will be more sensitive than other hindbrain sites to microinjections of an NPY- related agonist. What effect do lesions of this sensitive locus have on ad libitum and deprivation-induced food intake? What is the origin of NPY afferents to this locus? Experiments addressing this question will employ retrograde labeling methods combined with immunostaining for NPY. What is the distribution and binding characteristics of the specific NPY receptor subtypes that mediate NPY's effects on food intake? For these experiments we will combine behavioral methods using microinjection of NPY receptor agonists and antagonists with receptor binding methods using quantitative autoradiography. The major emphasis of this proposal is on NPY afferents in the dorsal pons and the locus or synaptic field where NPY acts to stimulate food intake. Towards the long range aim of mapping the larger NPY neural circuitry, I propose additionally to investigate NPY gene expression in response to food deprivation in locus coeruleus and dorsal tegmental nuclei, two dorsal pontine loci with NPY efferent projections to forebrain and perhaps hindbrain targets involved in NPY-stimulated food intake. The hindbrain locus for NPY action in feeding is a doorway through which to approach the broader neural circuitry regulating energy balance. I plan as long term goals to characterize the functional and anatomical relationship between NPY and other neuro- transmitters, and the relationship between hindbrain and hypothalamic neural substrates involved in the control of food and regulation of body weight. Results will contribute to the overall understanding of the neurobiology underlying obesity and eating disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK055829-02
Application #
6178053
Study Section
Special Emphasis Panel (ZRG1-IFCN-2 (01))
Program Officer
Smith, Philip F
Project Start
1999-05-01
Project End
2003-04-30
Budget Start
2000-05-01
Budget End
2001-04-30
Support Year
2
Fiscal Year
2000
Total Cost
$161,715
Indirect Cost
Name
University of Massachusetts Amherst
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
153223151
City
Amherst
State
MA
Country
United States
Zip Code
01003
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Jones, Juli E; Corp, Eric S (2003) Effect of naltrexone on food intake and body weight in Syrian hamsters depends on metabolic status. Physiol Behav 78:67-72
Jones, Juli E; Pick, Rebecca R; Davenport, Matthew D et al. (2002) Disinhibition of female sexual behavior by a CRH receptor antagonist in Syrian hamsters. Am J Physiol Regul Integr Comp Physiol 283:R591-7
Corp, E S; McQuade, J; Krasnicki, S et al. (2001) Feeding after fourth ventricular administration of neuropeptide Y receptor agonists in rats. Peptides 22:493-9
Jones, J E; Corp, E S; Wade, G N (2001) Effects of naltrexone and CCK on estrous behavior and food intake in Syrian hamsters. Peptides 22:601-6
Corp, E S; Greco, B; Powers, J B et al. (2001) Neuropeptide Y inhibits estrous behavior and stimulates feeding via separate receptors in Syrian hamsters. Am J Physiol Regul Integr Comp Physiol 280:R1061-8