ASSESSMENT OF FEEDING RESPONSE OF TUMOR-BEARING RATS TO HYPOTHALAMIC INJECTION AND INFUSION OF NEUROPEPTIDE-Y

Tumor-bearing rats exhibited significant decreases in 1- to 4-h intake of rat chow following the intrahypothalamic injection of 2 mu g neuro peptide Y (NPY). This refractory feeding response was present prior to the onset of anorexia and became more severe as anorexia worsened. Th e constant infusion of NPY (125 ng/h) into the perifornical hypothalam us of TB and control rats elicited increased feeding for only 2 days. Because chromatography revealed minipump NPY to be intact after 10 inf usion days, downregulation of NPY receptors may have occurred. Daily i njection of increasing doses of NPY stimulated ad rib feeding in non-T B rats, while having no effect on TB rats. Desensitization to NPY-indu ced feeding following daily injections of the peptide was suggested by the loss of feeding response to a dose (500 ng) of NPY that increased food intake prior to the daily NPY treatments. These results suggest that hypothalamic NPY feeding systems are refractory in TB rats, even before they exhibit anorexia. In addition, a rapid loss of the feeding response occurred in rats with constant infusion of NPY into hypothal amic tissue or with daily intrahypothalamic injections of the peptide, suggesting possible NPY receptor-mediated alterations. Therefore, con trol of obesity or anorexia through NPY feeding mechanisms may prove d ifficult due to rapid compensatory receptor changes.