NEUROCHEMICAL EFFECTS OF NEUROPEPTIDE-Y (NPY) AND NPY2-36

Our previous in vivo structure-activity studies suggested that the put ative receptors mediating the effects of NPY and NPV2-36 on food intak e and body temperature following ICV administration are pharmacologica lly different. In the present study, we examined and compared dose rel ated effects of NPY and NPY2-36 on levels of norepinephrine (NE), dopa mine (DA) and its main metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA), as well as serotonin (5-HT) and its metab olite, 5-hydroxyindolacetic acid (5-HIAA), in several brain regions of the rat, including: frontal cortex, hypothalamus, amygdala, septum, n ucleus accumbens, corpus striatum, globus pallidus, substantia nigra a nd hippocampus. NPY and NPY2-36 (10 or 20 mu g) were administered intr aventricularly and the regional levels of the amines and metabolites w ere assessed 30 min following administration. Results indicate that bo th doses of NPY decreased NE levels within the hypothalamus. Furthermo re, DOPAC concentrations were increased in this region while DA and HV A remained unchanged. The most pronounced neurochemical effects of NPY were found in the hippocampus, where the peptide produced dose relate d increases in DA, DOPAC and HVA. On the other hand, NPV2-36 significa ntly increased NE, DA and its metabolite DOPAC in both the amygdala an d septum. The metabolism of DA was most obviously affected in the hipp ocampus and frontal cortex where levels of DA and DOPAC were significa ntly increased. 5-HT was affected in both the hypothalamus and globus pallidus where DA and its metabolite HVA were also increased. These re sults indicate that although NPV is abundantly distributed throughout the CNS, its effects on biogenic amine metabolism are limited and that the effects of NPY2-36 are actually more pervasive and prominent than those produced by the parent peptide. The implications of these neuro chemical changes in the differential neurobehavioral effects of both p eptides will be discussed.