Neuropeptide Y, but not agouti-related peptide or melanin-concentrating hormone, is a target peptide for orexin-A feeding actions in the rat hypothalamus.

We examined the effects of orexin A on the mRNA levels of neuropeptide Y, agouti-related peptide, melanin-concentrating hormone, prepro-orexin and orexin receptors in the rat hypothalamus. Adult male rats were treated centrally (i.c.v.) with a single dose of orexin A (3 nmol). After 2, 6 and 12 h, neuropeptide Y, agouti-related peptide, melanin-concentrating hormone, and prepro-orexin mRNA levels were measured by semiquantitative RT-PCR and in situ hybridization; orexin receptors mRNA content was quantified by semiquantitative RT-PCR. We found that orexin A increased neuropeptide Y expression in the arcuate nucleus of the rat hypothalamus. This stimulatory effect was transient, being observed 2 h after the treatment, and disappearing after longer periods (6 and 12 h). In contrast, no change was demonstrated in hypothalamic agouti-related peptide, melanin-concentrating hormone, prepro-orexin or orexin receptors mRNA levels at any time evaluated. Our results suggest that neuropeptide Y synthesized in the arcuate nucleus of the hypothalamus, but not agouti-related peptide and melanin-concentrating hormone pathways, is likely involved in orexin-induced feeding behavior, and raise the possibility that this functional linkage may also be involved in other actions mediated by orexins such as locomotor activity and sympathetic function. Copyright 2002 S. Karger AG, Basel