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

Our previous in vivo structure-activity studies suggested that the putative receptors mediating the effects of NPY and NPV2-36 on food intake and body temperature following ICV administration are pharmacologically different. In the present study, we examined and compared dose related effects of NPY and NPY2-36 on levels of norepinephrine (NE), dopamine (DA) and its main metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA), as well as serotonin (5-HT) and its metabolite, 5-hydroxyindolacetic acid (5-HIAA), in several brain regions of the rat, including: frontal cortex, hypothalamus, amygdala, septum, nucleus accumbens, corpus striatum, globus pallidus, substantia nigra and hippocampus. NPY and NPY2-36 (10 or 20 mu g) were administered intraventricularly and the regional levels of the amines and metabolites were assessed 30 min following administration. Results indicate that both doses of NPY decreased NE levels within the hypothalamus. Furthermore, DOPAC concentrations were increased in this region while DA and HVA remained unchanged. The most pronounced neurochemical effects of NPY were found in the hippocampus, where the peptide produced dose related increases in DA, DOPAC and HVA. On the other hand, NPV2-36 significantly increased NE, DA and its metabolite DOPAC in both the amygdala and septum. The metabolism of DA was most obviously affected in the hippocampus and frontal cortex where levels of DA and DOPAC were significantly increased. 5-HT was affected in both the hypothalamus and globus pallidus where DA and its metabolite HVA were also increased. These results 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 neurochemical changes in the differential neurobehavioral effects of both peptides will be discussed.