Considerable evidence suggests that NPY stimulates feeding in rats in a site-specific manner in the brain. We propose to test the hypothesis that in the rate NPY may be an orexigenic, peptidergic signal with a pivotal role in the control of daily food intake. Six series of experiments are proposed. In the first three series, we propose to establish a relationship between NPY output and food intake by assessing NPY release in three experimental paradigms: (a) in association with the daily food intake pattern, (b) in response to acute food deprivation followed by food intake and (c) in response to experimental manipulation that produces hyperphagia or reduced food intake. In two additional experimental series we will examine the mechanism of NPY action in relation to the source of NPY that may normally be responsible for daily food intake pattern and the nature of the interaction with adrenergic transmitters for the brain stem where NPY and adrenergic transmitters coexist. In the final, experiment, we will compare the structure-function relationship among NPY, NPY fragments, peptide YY (PYY), PYY fragments and analogs with special emphasis on their excitatory and inhibitory effects on the microstructure of feeding behavior. The major techniques to be employed are quantitation by radioimmunoassay of NPY release in vivo (push-pull perfusion) and in vitro (incubations) from specific hypothalamic sites implicated in the control of feeding. Additionally, we will employ stereotaxic procedures for brain cannulation, lesions and deafferentation and administer pharmacologic anorectic drugs. The outcome of these studies is likely to support the view that physiological and experimental conditions that promote feeding may involve NPY as a signal in a site-specific manner.
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