NEUROPEPTIDE-Y AND FOOD-INTAKE IN FASTED RATS - EFFECT OF NALOXONE AND SITE OF ACTION

Central administration of neuropeptide Y (NPY) induces food intake in freely feeding animals and this effect is mediated by hypothalamic sites. Little is known, however, about the effect of NPY on food intake and site of action in food-deprived animals. To examine this further, 24-h fasted rats received injections of saline or NPY into the lateral cerebral ventricle (10-mu-g/10-mu-l; n = 8) or into the lateral (LH) or ventromedial hypothalamus (VMH) (1-mu-g/0.5-mu-l; n = 44). In addition, intracerebroventricular (i.c.v.) injections of NPY were carried out with or without i.c.v. naloxone (25-mu-g), a specific opioid receptor antagonist. During the first 40 min food intake was not different with or without NPY. After 60 and 120 min, food intake was 5.9 +/- 0.4 g and 8.3 +/- 0.6 g with i.c.v. saline which was significantly augmented by i.c.v. NPY to 8.7 +/- 0.9 g and 14.4 +/- 1.5 g, respectively (P < 0.05). This increase in food consumption was due to a prolongation of feeding time. The opioid receptor antagonist naloxone significantly augmented latency to feed, both in the absence and presence of NPY (8.0 vs 1.7 min or 14.7 vs 2.8 min, respectively) and abolished the NPY-induced increase in food intake. Following intrahypothalamic injection of NPY, an increase in food intake (> 20%) was observed in 50% of the histologically identified LH and VMH sites, but only in 15% of the injection sites outside the LH/VMH. Mean food intake 0-60 min was 4.6 g (NPY) vs 3.9 g (saline) following injection into the LH and 6.4 g (NPY) vs 5.5 g (saline) following injection into the VMH, which was statistically not different. These data demonstrate that NPY effectively stimulates food intake in fasted rats. It does not, however, augment the natural food deprivation induced stimulus of food intake. The action of NPY appears to be related to interference with satiety signals and is mediated by endogenous opioid receptors. In contrast to the satiated state, microinjection of NPY into discrete sites within the LH or VMH of fasted rats does not unequivocally reflect the potent action of NPY observed after i.c.v. injection, suggesting that other central sites may be of relevance.