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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 if ghrelin modulates food cue learning. Here we show using functional magnetic resonance imaging 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 hippocampus and ventral striatum. Our work demonstrates that ghrelin promotes the ability of cues to acquire incentive salience, and has implications for the development of vulnerability to obesity.