The long-term goals of this research are to determine the role of hypothalamic neuropeptide Y (NPY) in natural feeding behavior, as well as in disorders of eating behavior and body weight control. 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 of this peptide induces hyperphagia and obesity. These eating stimulatory effects of NPY are dependent upon the presence of the adrenal hormone corticosterone (CORT). Experiments in humans with eating disorders have also revealed that symptoms of anorexia nervosa and bulimia are associated with alterations in brain levels of NPY and related peptides. The proposed studies, conducted for the most part in adult rats with chronic hypothalamic guide cannulas, will investigate the neurocircuitry underlying the NPY-induced eating response, the specific influence of endogenous NPY in spontaneously occurring eating, and the mechanisms of this system's interactions with CORT. These issues will be investigated through studies employing: 1) the metabolic tracer [14C]2C-deoxyglucose to define the brain areas activated by NPY microinjection; 2) automated measures of minute-to-minute eating behavior to delineate the temporal pattern of meal-taking elicited by NPY; 3) injections of NPY at different phases of the day/night cycle to define the circadian rhythms of responsiveness to this peptide; 4) injection of NPY antisera in food deprived and spontaneously-feeding animals to determine NPY's role in these behaviors; and 5) central implants of crystallin CORT to clarify the brain sites mediating its interactions-with the NPY system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS024268-07
Application #
3408664
Study Section
Biopsychology Study Section (BPO)
Project Start
1986-12-01
Project End
1994-11-30
Budget Start
1992-12-01
Budget End
1993-11-30
Support Year
7
Fiscal Year
1993
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
Khan, A M; Curras, M C; Dao, J et al. (1999) Lateral hypothalamic NMDA receptor subunits NR2A and/or NR2B mediate eating: immunochemical/behavioral evidence. Am J Physiol 276:R880-91
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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