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.
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