HYPOTHALAMIC NEUROTRANSMITTER SYSTEMS & EATING BEHAVIOR

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Peptides in the brain are known to modulate eating behavior and body weight gain. This proposal will focus on a specific peptide, neuropeptide Y (NPY), which is very abundant in the brain and is found to be particularly potent in stimulating eating behavior in a variety of species. While evidence indicates that NPY may have a selective stimulatory effect on the ingestion of carbohydrate and that NPY synthesized in the hypothalamus may be activated under conditions of negative energy balance, the specific function of this peptide in controlling natural ingestive behavior remains to be defined. This constitutes the purpose of the proposed experiments in rats, which have 7 Specific Aims. These are: l) to characterize, using computer-automated procedures, the effects of hypothalamic injection of NPY agonists and antagonists on the rats' patterns of macronutrient intake; 2) to use central injection and lesion techniques to evaluate the importance of specific hypothalamic nuclei in mediating the action of NPY on carbohydrate ingestion; 3) to employ biochemical techniques to examine, in adrenalectomized animals, the impact of the glucocorticoid, corticosterone (CORT), on NPY gene expression and NPY levels in the hypothalamus; 4) to investigate using biochemical procedures shifts in NPY and its gene expression, in relation to circulating CORT, across the light/dark cycle; 5) to examine, through biochemical and behavioral measures, the functional significance of the interaction between hypothalamic NPY and circulating CORT, in relation to the rise in carbohydrate ingestion at the onset of the active dark period; 6) to investigate whether hypothalamic NPY, possibly in association with CORT, is active in modulating carbohydrate intake before puberty and whether it contributes to gender differences in preference for this nutrient; and 7) to examine the impact of short-term food deprivation on hypothalamic NPY levels, NPY gene expression and circulating CORT. The ultimate goal of these proposed experiments is to understand the significance of the clinical findings that patients with anorexia nervosa or bulimia exhibit disturbances in CSF levels of NPY or a related peptide, which are associated with alterations in CSF cortisol levels as well as changes in carbohydrate ingestion.