INSATIABLE FEEDING EVOKED IN RATS BY RECURRENT PERFUSION OF NEUROPEPTIDE-Y IN THE HYPOTHALAMUS

Hyperphagic-like intake of food was determined in the unrestrained rat during the sustained elevation over time of neuropeptide Y (NPY) within the paraventricular nucleus (PVN) and surrounding hypothalamic regions. A single guide tube was implanted stereotaxically in each of 22 rats for localized, intermittent perfusions of a CSF vehicle, nondeprotected NPY (1-36) or native NPY. Each site in the PVN of the fully sated rat was perfused repeatedly over a 5.0-h interval by means of a standard push-pull cannula system at a rate of 20-mu-l/min for 6.0 min in one of three concentrations: 0.2, 1.0 and 2.0-mu-g/min. Two perfusions of 1.0-mu-g/min NPY evoked an intake of 4.6 +/- 1.1 g of food over a 3.0-h period, whereas 4-7 and 8-15 perfusions of this concentration of NPY, distributed over 5.0 h, induced the sated rats to eat a total of 12.0 +/- 1.1 g and 33.2 +/- 3.0 g, respectively. During a fixed number of 10 hypothalamic perfusions distributed over 5.0 h, concentrations of 0.2 and 2.0-mu-g/min NPY caused a cumulative intake of food in the rats of 14.2 +/- 2.0 g and 31.7 +/- 3.3 g, respectively. Under each condition, parallel push-pull perfusions of either control solution in the same hypothalamic sites were without effect on feeding. During the 5.0-h interval of repeated perfusions, successive bouts of eating occurred with individual intakes of food reaching as high as 49.0 g, which exceeded by up to two-fold the entire daily consumption of food. However, ingestion of water was unaffected by perfusion of NPY. These results show that unlike the stimulating effects on feeding of other neuroactive factors, NPY creates a hunger which is not satiable as long as the level of NPY in the hypothalamus is chronically elevated over time. Further, should such an elevated level of hypothalamic NPY be maintained, the normal long-term regulation of caloric intake would be displaced, resulting in unremitting overeating and ultimate obesity.