Chronic and continuous intracerebroventricular infusion of neuropeptide Y in Long-Evans rats mimics the feeding behaviour of obese Zucker rats

Neuropeptide Y (NPY), a member of the pancreatic polypeptide family strongly stimulates food intake when injected centrally in animals. It is found in abundance in the brain and particularly in areas involved in the regulation of feeding behaviour. Moreover, in these areas, NPY concentrations are higher in the obese hyperphagic Zucker rat. The aim of the present experiment was to reproduce in normal Long-Evans rats the high central levels of NPY measured in Zucker rats. We therefore continuously infused NPY in the brain lateral ventricle through osmotic mini-pumps and studied the effects of this infusion on different parameters of the feeding behaviour. Male adult Long-Evans rats were fed ad libitum on a high carbohydrate (HC) diet and on a high fat (HF) diet given simultaneously in two separate cups. NPY was infused at a rate of 0.44 micrograms/h (n= 11) and rats infused with artificial cerebrospinal fluid (n = 11) served as controls. The infusions lasted 14 days. Total food intake markedly increased in NPY infused rats starting on the first day after pump installation (33.7 +/- 1.7 vs. 14.8 +/- 0.6 g/day; P < 0.0001). This effect lasted for nine days. In these rats, the average food intake during the infusion period (21.0 +/- 1.6 g/day) was also significantly greater than during the pre-infusion period (13.1 +/- 0.5 g/day; P < 0.0001) and the post-infusion period (10.6 + 0.4 g/day; P < 0.0001). This increase was mainly due to an increased intake of HC diet that followed the variations of total food intake and to a lesser extent to the increase in the HF intake that lasted during the five first days of infusion only. NPY infused rats weighed significantly more than the controls and developed abdominal fat mass but their body weight plateaued during the last five days of infusion. The dark light (D/L) pattern was also largely modified by NPY infusion. The D/L ratio for HC intake fell from a value of 4.29 +/- 0.40 to 1.39 +/- 0.07 (P < 0.0001) in the NPY infused rats, with effects lasting during the whole infusion period. The D/L ratio for HF intake was slightly modified during the first days of infusion only. The chronic ICV infusion of neuropeptide Y therefore reproduced the modifications of the eating behaviour observed in the Zucker fatty rat (hyperphagia, overweight, nutrient preference and disturbed diurnal pattern of food intake). The present results support our hypothesis of an important role of NPY in the development of these syndromes. The decreased effects of NPY on body weight and food intake after nine days of continuous infusion might be relevant to the establishment in normal rats of counter-regulatory mechanisms that might be lacking in the obese Zucker rat.