RESPONSE OF NEUROPEPTIDE Y-DEFICIENT MICE TO FEEDING EFFECTORS

Neuropeptide Y (NPY) is thought to be an important central regulator o f feeding behavior and body weight. However, mice lacking NPY due to t argeted genetic deletion do not display abnormalities in food intake o r body weight with ad libitum access to food or in response to fasting . In this study, we investigate the response of NPY-deficient (NPY-/-) mice to anorexic and orexigenic treatments. The dose-dependent stimul ation of food intake by central NPY administration was unaltered in NP Y-/- mice. Peripheral administration of various doses of leptin for 2 days elicited a two-fold greater inhibition of food intake in NPY-/- m ice than in wildtype (NPY+/+) mice. In addition, lateral ventricular a dministration of leptin (1 mu g) suppressed refeeding in NPY-/- mice a fter a 24 h fast, but had little effect in NPY+/+ mice. However, the r esponse to other feeding inhibitors such as corticotrophin releasing f actor (CRF), dexfenfluramine, and a melanocortin 4 receptor (MC4R) ago nist, MTII, was unaltered in NPY-/- mice. These results indicate that the appetite-suppressant action of exogenous leptin is uniquely amplif ied in NPY-/- mice, and suggest that NPY may tonically antagonize lept in action. (C) 1998 Published by Elsevier Science B.V. All rights rese rved.