Blockade of natural and neuropeptide Y-induced carbohydrate feeding by a receptor antagonist PYX-2.

Neuropeptide Y (NPY injected into the paraventricular nucleus (PVN) of rats has a potent stimulatory effect specifically on carbohydrate intake. This study examined the behavioral effects of a newly synthesized NPY antagonist, PYX-2. After PVN injection of PYX-2 (50-900 pmoles) alone, a strong dose-dependent reduction in spontaneous carbohydrate intake at the onset of the dark cycle was observed in freely-feeding rats. Moreover, at even lower doses (12.5 and 25.0 pmoles), PYX-2 also blocked the stimulatory action of PVN NPY (100 pmoles) on carbohydrate ingestion. These results provide the first evidence for the existence of endogenous NPY receptors in mediating the action of exogenous NPY in the hypothalamus. They also constitute a crucial step in demonstrating a physiological function of these PVN NPY receptors specifically in controlling carbohydrate ingestion at the onset of the natural feeding cycle.