In vitro rat hypothalamic slices were used to examine the ability of neuropeptide Y (NPY), and the putative Y-1 and Y-2 receptor agonists [Pro(34)]NPY and [C-2]NPY, to modify spontaneous single-neuron discharge in the paraventricular nucleus (PVN). NPY and [Pro(34)]NPY, at high concentrations (1500 nM), decreased discharge rates. At intermediate concentrations (150 nM) these peptides produced multiple effects, including increases, decreases, and biphasic changes. At lower concentrations (0.15-15 nM), they typically increased discharge rates. In contrast, [C-2]NPY, at all concentrations (1.5-1500 nM), predominantly increased discharge rates. Thus, these NPY subtype agonists have multiple effects on discharge rate, which may be due to actions on multiple NPY receptor subtypes. Copyright (C) 1996 Elsevier Science Inc.