EVIDENCE FOR INVOLVEMENT OF NEUROPEPTIDE-Y RECEPTORS IN THE REGULATION OF FOOD-INTAKE - STUDIES WITH Y-1-SELECTIVE ANTAGONIST BIBP3226

1. Experiments were conducted to evaluate the effects of the novel non -peptide neuropeptide Y Y-1 receptor antagonist, BIBP3226 nylacetyl)-N -[(4-hydroxy-phenyl)methyl]-D-arginine amide) on spontaneous, fasting- induced and NPY-induced food intake in rats. In addition to consumptio n of regular chow, the effects of BIBP3226 on consumption of highly pa latable sweetened mash were monitored in a 1 h test on first exposure and after familiarization with novel food. 2 BIBP3226 (10.0 nmol, i.c. v.) had no effect on the consumption of regular chow, but reduced sign ificantly the intake of highly palatable diet and the food intake stim ulated by fasting (24 h). Neuropeptide Y (NPY, 1.0 nmol, i.c.v.) signi ficantly increased the consumption of regular rat chow. This orexigeni c effect of NPY was blocked by BIBP3226 (10.0 nmol, administered i.c.v . 5 min before NPY) at 30 min and 4 h, but not at 1 and 2 h. When anim als were pretreated with diazepam (0.5 mg kg(-1), i.p., 20 min before NPY), BIBP3226 failed to suppress NPY-induced feeding. 3 An NPY Y-1 an d Y-3 receptor agonist, [Leu(31),Pro(34)]NPY and a Y-5 receptor agonis t human peptide YY3-26 (hPYY(3-36), both 30 pmol), microinjected into the paraventricular nucleus of the hypothalamus (PVN) increased the co nsumption of regular rat chow. BIBP3226 (0.4 nmol, into the PVN) compl etely blocked the stimulatory effect of [Leu(31),Pro(34)]NPY but not t hat of hPYY(3-36) BIBP3226 (0.4 nmol) alone failed to modify the consu mption of the regular chow. Higher doses of BIBP3226 (1.0 and 2.0 nmol ) injected into the vicinity of the PVN reduced the consumption of the sweetened mash. 4 These results suggest that both the NPY Y-1 and Y-5 receptors in the PVN are involved in the regulation of food intake. T he stimulatory effect of exogenous NPY is probably mediated through an NPY receptor subtype that is not identical with the Y-1 receptor (pos sibly Y-1 receptor). However, the NPY Y-1 receptors may mediate the ef fect of endogenous NPY in conditions of increased energy demand or on intake of highly palatable diets.