Actions of leptin on growth hormone secretagogue-responsive neurones in the rat hypothalamic arcuate nucleus recorded in vitro

In the arcuate nucleus, the growth hormone (GH) secretagogue (GHS)-responsi ve cells include a subpopulation of the neuropeptide Y (NPY) neurones. It i s not known whether these include the orexigenic NPY population that are in hibited by the satiety hormone, leptin. Thus we investigated whether (i) th e arcuate nucleus cells electrically excited by GHS are inhibited by leptin and(ii) chronic central leptin infusion alters GHS-induced Fos expression. Of 36 cells recorded from a trimmed hypothalamic slice containing arcuate nucleus, 13 cells were excited by the nonpeptide GHS, CP-459,599. The predo minant response of these cells to leptin was inhibitory: six inhibited, thr ee excited and four unresponsive. Similar responses were observed in a popu lation of arcuate cells recorded from a preparation in which synaptic trans mission was blocked, suggesting that leptin acts directly on a subpopulatio n of GHS-responsive neurones. Intracerebroventricular infusion of leptin fo r 1 week did not alter the number of cells expressing Fos following GHS adm inistration. Thus, while leptin does not appear to influence the central ac tions of GHS to induce immediate early gene expression, it does act directl y on a subpopulation of cells excited by GHS, eliciting mostly inhibitory b ut also some excitatory responses. It will be interesting to discover the c onsequences of leptin's inhibitory effects on the hypothalamic circuits exc ited by GHS, particularly since leptin paradoxically has a stimulatory effe ct on GH secretion, presumed to reflect a suppression of central NPY pathwa ys.