NEURAL SUBSTRATES FOR LEPTIN AND NEUROPEPTIDE-Y (NPY) INTERACTION - HYPOTHALAMIC SITES ASSOCIATED WITH INHIBITION OF NPY-INDUCED FOOD-INTAKE

Intracerebroventricular (i.c.v.) injection of leptin, the adipocyte ho rmone, inhibits neuropeptide Y (NPY)-induced feeding in the rat. To id entify the neural substrate for leptin and NPY interaction in the hypo thalamus, we evaluated the expression of c-fos-like immunoreactivity ( FLI), an early marker of neuronal activation, in response to icy admin istration of leptin, NPY and leptin plus NPY. As expected, leptin sign ificantly decreased NPY-induced feeding in leptin plus NPY-treated rat s. A comparative evaluation of the number of FLI-positive neurons in h ypothalamic sites showed that both leptin and NPY activated FLI in the parvocellular subdivision of the paraventricular nucleus (pPVN), dors omedial nucleus (DMN) and ventromedial nucleus (VMN). NPY also augment ed the FLI response in the magnocellular PVN (mPVN) and supraoptic nuc leus (SON), two sites where leptin alone was ineffective. Combined lep tin and NPY treatment significantly decreased the number of FLI-positi ve neurons in the magnocellular PVN but increased their number in the dorsomedial nucleus as compared to the number of FLI-expressing neuron s in these sites after NPY and leptin alone. Because there is morpholo gic evidence of a link between magnocellular PVN and dorsomedial nucle us, these results suggest the functional involvement of leptin plus NP Y responsive elements in these sites in reduction of NPY-induced feedi ng by leptin. (C) 1998 Elsevier Science Inc.