Ghrelin Enhances Food Odor Conditioning in Healthy Humans: An fMRI Study

Vulnerability to obesity includes eating in response to food cues, which acquire incentive value through conditioning. The conditioning process is largely subserved by dopamine, theorized to encode the discrepancy between expected and actual rewards known as the reward prediction error (RPE). Ghrelin is a gut-derived homeostatic hormone that triggers hunger and eating. Despite extensive evidence that ghrelin stimulates dopamine, it remains unknown in humans whether ghrelin modulates food cue learning. Here, we show using fMRI that intravenously administered ghrelin increased RPE-related activity in dopamine-responsive areas during food odor conditioning in healthy volunteers. Participants responded faster to food odor-associated cues and perceived them to be more pleasant following ghrelin injection. Ghrelin also increased functional connectivity between the hippocampus and the ventral striatum. Our work demonstrates that ghrelin promotes the ability of food cues to acquire incentive salience and has implications for the development of vulnerability to obesity. [Display omitted] •fMRI reveals reward prediction error-related activity in dopamine projection sites•Intravenous ghrelin enhances food odor conditioning in human volunteers•Ghrelin also increases prediction error and value signals in striatum and hippocampus•Hippocampus-striatum functional connectivity is also increased by ghrelin The appetite-stimulating hormone ghrelin increases dopamine neuron burst firing. Reinforcement learning is driven by reward prediction errors, which are encoded by dopamine firing. Han et al. use fMRI to show that intravenous ghrelin in human volunteers increases reward prediction error signaling and conditioning to food odors.