Ghrelin Drives Food Intake by Attentional Bias Toward Food Cues.

Food-predictive cues can promote eating, but the contribution of metabolic signals to cue-guided behavior remains incompletely understood. Ghrelin is an orexigenic hunger hormone that has previously been linked to behavioral and neural responses to food-predictive cues, although many paradigms cannot distinguish general hunger-driven intake from intake expressed in response to discrete conditioned cues. We developed a home-cage operant task using the Feeding Experimentation Device 3 (FED3) to assess attention-linked responding to an illuminated food-predictive food cue in male mice. Following staged training, eight mice were tested under fed, overnight-fasted and ghrelin-treated conditions in a crossover design. Fasting and ghrelin increased correct and premature responses, and reduced omissions, indicating enhanced engagement with the conditioned food cue, with motivational and impulsivity-related processes likely contributing to the behavioral profile. Ghrelin increased food intake during the cue-guided task but not during FreeFeeding in the absence of the illuminated predictive cue, whereas fasting increased intake in both contexts. The maximum obtainable food intake was elevated by fasting and ghrelin, but only during the cue-guided task. These findings establish a home-cage FED3-based paradigm for resolving multiple attention-linked components of food-cue responding and show that acute ghrelin and fasting produce overlapping effects on cue-guided engagement but differ in their effects on food intake across task contexts, with ghrelin preferentially increasing intake when food availability is signaled by a conditioned cue.