Influence of ghrelin on the central serotonergic signaling system in mice

The central ghrelin signaling system engages key pathways of importance for feeding control, recently shown to include those engaged in anxiety-like behavior in rodents. Here we sought to determine whether ghrelin impacts on the central serotonin system, which has an important role in anxiety. We focused on two brain areas, the amygdala (of importance for the mediation of fear and anxiety) and the dorsal raphe (i.e. the site of origin of major afferent serotonin pathways, including those that project to the amygdala). In these brain areas, we measured serotonergic turnover (using HPLC) and the mRNA expression of a number of serotonin-related genes (using real-time PCR). We found that acute central administration of ghrelin to mice increased the serotonergic turnover in the amygdala. It also increased the mRNA expression of a number of serotonin receptors, both in the amygdala and in the dorsal raphe. Studies in ghrelin receptor (GHS-R1A) knock-out mice showed a decreased mRNA expression of serotonergic receptors in both the amygdala and the dorsal raphe, relative to their wild-type littermates. We conclude that the central serotonin system is a target for ghrelin, providing a candidate neurochemical substrate of importance for ghrelin's effects on mood.