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 microliters/min for 6.0 min in one of three concentrations: 0.2, 1.0 and 2.0 micrograms/min. Two perfusions of 1.0 micrograms/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 micrograms/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.(ABSTRACT TRUNCATED AT 250 WORDS)