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.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Biopsychology Study Section (BPO)
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Rockefeller University
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New York
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