The long-term goals of this line of research are to determine the role of hypothalamic neuropeptide Y (NPY) in normal feeding, as well as in excessive eating and obesity. Experiments in rats have demonstrated that, acute medial hypothalamic microinjection of NPY produces a dramatic eating response and a strong preference for carbohydrate, and that chronic administration induces hyperphagia and obesity. The proposed studies, conducted for the most part in adult rats with chronic hypothalamic guide cannulas, will investigate the brain site(s), neural pathways, receptor types and peripheral hormones which mediate the NPY-induced feeding behavior. These issues will be investigated through studies employing: cannula-mapping to determine the most sensitive hypothalamic site(s) for NPY feeding; hypothalamic NPY microinjection in combination with midbrain knife cuts to determine the trajectory of the neural pathways which mediate the eating response; injection of NPY, related peptides, peptide fragments as well as antagonists of other neurotransmitters to elucidate the relevant receptor types involved; and adrenalectomy with corticosterone replacement to investigate the role of adrenal glucocorticoids in NPY-induced feeding. Two experiments will investigate whether endogenous hypothalamic NPY is released in relation to feeding; one by determining the impact of antisera to NPY on normal and deprivation-induced feeding, and the other by measuring changes in the levels of endogenous NPY (by radioimmunoassay) within discrete brain areas during food deprivation and during feeding. Finally, one experiment will examine the impact of macronutrients on the development of obesity induced by chronic NPY injection, and another experiment will examine changes in endogenous levels of NPY during the development of obesity induced by highly palatable, calorically dense diets.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
7R01NS024268-04
Application #
3408665
Study Section
Biopsychology Study Section (BPO)
Project Start
1986-12-01
Project End
1990-03-31
Budget Start
1989-09-01
Budget End
1990-03-31
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of California Riverside
Department
Type
Schools of Arts and Sciences
DUNS #
City
Riverside
State
CA
Country
United States
Zip Code
92521
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Marin Bivens, C L; Thomas, W J; Stanley, B G (1998) Similar feeding patterns are induced by perifornical neuropeptide Y injection and by food deprivation. Brain Res 782:271-80
Gillard, E R; Khan, A M; Mouradi, B et al. (1998) Eating induced by perifornical cAMP is behaviorally selective and involves protein kinase activity. Am J Physiol 275:R647-53
Gillard, E R; Khan, A M; Grewal, R S et al. (1998) The second messenger cAMP elicits eating by an anatomically specific action in the perifornical hypothalamus. J Neurosci 18:2646-52
Gillard, E R; Khan, A M; Ahsan-ul-Haq et al. (1997) Stimulation of eating by the second messenger cAMP in the perifornical and lateral hypothalamus. Am J Physiol 273:R107-12
Stanley, B G; Butterfield, B S; Grewal, R S (1997) NMDA receptor coagonist glycine site: evidence for a role in lateral hypothalamic stimulation of feeding. Am J Physiol 273:R790-6
Aramakis, V B; Stanley, B G; Ashe, J H (1996) Neuropeptide Y receptor agonists: multiple effects on spontaneous activity in the paraventricular hypothalamus. Peptides 17:1349-57
Stanley, B G; Willett 3rd, V L; Donias, H W et al. (1996) Lateral hypothalamic NMDA receptors and glutamate as physiological mediators of eating and weight control. Am J Physiol 270:R443-9
Gillard, E R; Dang, D Q; Stanley, B G (1993) Evidence that neuropeptide Y and dopamine in the perifornical hypothalamus interact antagonistically in the control of food intake. Brain Res 628:128-36
Stanley, B G; Thomas, W J (1993) Feeding responses to perifornical hypothalamic injection of neuropeptide Y in relation to circadian rhythms of eating behavior. Peptides 14:475-81

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