Neuropeptide Y (NPY) given by the intracerebroventricular (ICV) route in the rat evokes hyperphagic-like feeding. To examine the molecular nature of action of NPY, comparisons were made between the central effects of this peptide and a newly synthesized amino-terminus fragment, NPY1-27. A single guide tube was implanted stereotaxically to rest just above a lateral cerebral ventricle so that ICV injections in a volume of 10 microliters of either CSF control vehicle or peptide could be given in the unrestrained rat. Native NPY or NPY1-27 was given in doses of 5.0 or 10.0 micrograms, whereas nondeprotected NPY was infused in a dose of 10.0 micrograms. The intakes of either regular commercial rat diet or specially prepared chocolate-flavored biscuits as well as water were recorded intermittently for 4.0 h following each ICV infusion. Although a clear-cut dose response with a latency of similar magnitude emerged for both molecules, NPY was found to be nearly twice as potent as NPY1-27 in inducing spontaneous feeding. A corresponding infusion in the same volume of either nondeprotected NPY or CSF control vehicle was without effect. When chocolate-flavored biscuits were provided to the rat, an ICV infusion of a 10.0 micrograms dose of NPY enhanced significantly both rate of eating and total cumulative intake of flavored food in comparison to that after a similar infusion of NPY1-27 or either control solution. These results suggest that native NPY acting centrally affects gustatory and/or olfactory systems to a much greater degree than does NPY1-27.(ABSTRACT TRUNCATED AT 250 WORDS)