In a previous study, we have shown that neuropeptide Y inhibits the release of alpha-melanocyte-stimulating hormone from the rat hypothalamus in vitro. The aim of the present study was to investigate the possible effect of neuropeptide Y on the regulation of proopiomelanocortin-derived peptides in vivo. Rats received acute or chronic administration of neuropeptide Y in the lateral ventricle and the amount of alpha-melanocyte-stimulating hormone was measured in the hypothalamus and in the neurointermediate lobe of the pituitary. In the same experiments, the amounts of corticotropin-releasing factor and corticotropin were quantified in the hypothalamus and anterior pituitary, respectively. Acute treatment with synthetic neuropeptide Y (0.1 to 10 micrograms/rat) did not modify the amount of alpha-melanocyte-stimulating hormone in the hypothalamus. In contrast, chronic infusion of neuropeptide Y (1.25 micrograms/h) over a seven day period significantly decreased the hypothalamic content of alpha-melanocyte-stimulating hormone, suggesting that neuropeptide Y regulates the synthesis and/or the processing of proopiomelanocortin. Concurrently, we found that both acute and chronic infusion of neuropeptide Y induced a significant reduction in corticotropin-releasing factor in the hypothalamus as well as a significant decrease in alpha-melanocyte-stimulating hormone and corticotropin in the neurointermediate and anterior lobes, respectively. Quantitative in situ hybridization histochemistry showed that chronic administration of neuropeptide Y also caused a reduction of proopiomelanocortin messenger RNA levels both in the intermediate and anterior lobes of the pituitary. Administration of neuropeptide Y (10(-6) M) on perifused rat hypothalamic slices caused a significant increase in corticotropin-releasing factor release.(ABSTRACT TRUNCATED AT 250 WORDS)