Ghrelin and Decision-Making: Exploring its Role in Food Reward, Novelty-Seeking, and Cost Valuation

When low energy levels are detected, Ghrelin, a peptide hormone, is produced in the fundus of the stomach. Referred to as the "hunger hormone", Ghrelin is traditionally associated with increased food intake and blood sugar levels. A key modulator in the gut-brain interaction, Ghrelin's growth hormone secretagogue receptor can be found widely across the cortico-striosomal circuit. Critical for decision-making, Ghrelin-based manipulation of this circuit can directly affect reward and cost valuation. While Ghrelin is uniformly considered to increase the valuation of food-based rewards, little research has explored its impact on non-food-based rewards or its effects on cost valuation. Therefore, to examine Ghrelin's effects on behavioral decision-making, rodents performed a series of fifteen behavioral tasks categorized into three contexts: food reward, novelty-seeking, and cost. Notably, in food-based tasks Ghrelin did not increase food-seeking but altered preference patterns, suggesting its role in modulating reward salience over hunger- driven motivation. Ghrelin did, however, increase novelty-seeking behavior in novelty tasks. This preference for novel rewards was retained even in the presence of well-known and novel food rewards, suggesting Ghrelin plays an active role in regulating exploratory behavior. Indicating its role in cost valuation, Ghrelin consistently increased cost aversion and competitive behaviors. A culmination of these results questions the traditional view of Ghrelin as a hunger signal. As demonstrated here, while Ghrelin drives reward-seeking, its effects are highly context-dependent and potentially alter risk sensitivity and persistence in goal-directed behavior. Elucidating Ghrelin's effects on decision-making has vast implications in studying the gut-brain interaction and its impact on metabolic or psychiatric disorders. Disorders such as depression, stress, obesity, and substance abuse commonly use overlapping circuitry and demonstrate altered reward processing, shifted cost valuation, and modified expression of Ghrelin. Future research aims to explore the neuronal mechanisms by which Ghrelin perturbed decision-making to better understand potential therapeutic targets for these disorders.