Rapid changes in the sensitivity of arcuate nucleus neurons to central ghrelin in relation to feeding status

Ghrelin, the endogenous ligand for the growth hormone secretagogue (GHS) receptor, stimulates feeding and increases body weight. Systemic ghrelin administration induces the immediate-early gene protein product, c-Fos, in the arcuate nucleus of the hypothalamus (ARC) of satiated rats and this increase is potentiated in fasted rats. The aim of this study was to determine whether potentiation was seen in fasted animals after intracerebroventricular (i.c.v) administration of ghrelin and to identify the hypothalamic nuclei activated by this peptide. In addition we investigated if allowing fasted animals to re-feed for 1 h prior to i.c.v. ghrelin injection affected the c-Fos response. Using c-Fos immunocytochemistry, we demonstrated that i.c.v. ghrelin activated several hypothalamic nuclei, including the ARC, paraventricular nucleus (PVH) and the lateral hypothalamus (LH). The c-Fos response was greater in fasted animals compared with satiated animals. Fasted rats allowed access to food for 1 h prior to central ghrelin administration showed an attenuated response in the ARC, similar to the response seen in fed animals. However, the response in the LH (including in the orexin neurons) was further potentiated. The latter may reflect a connection between the hypothalamus and regions of the brain responding to the reward value of the meal.