The antagonism of ghrelin alters the appetitive response to learned cues associated with food.

The rapid increase in obesity may be partly mediated by an increase in the exposure to cues for food. Food-paired cues play a role in food procurement and intake under conditions of satiety. The mechanism by which this occurs requires characterization, but may involve ghrelin. This orexigenic peptide alters the response to food-paired conditioned stimuli, and neural responses to food images in reward nuclei. Therefore, we tested whether a ghrelin receptor antagonist alters the influence of food-paired cues on the performance of instrumental responses that earn food and the consumption of food itself using tests of Pavlovian-to-instrumental transfer (PIT) and cue potentiated feeding (CPF), respectively. Food-deprived rats received Pavlovian conditioning where an auditory cue was paired with delivery of sucrose solution followed by instrumental conditioning to lever press for sucrose. Following training, rats were given ad libitum access to chow. On test day, rats were injected with the ghrelin receptor antagonist GHRP-6 [D-Lys3] and then tested for PIT or CPF. Disrupting ghrelin signaling enhanced expression of PIT. In addition, GHRP-6 [D-Lys3] impaired the initiation of feeding behavior in CPF without influencing overall intake of sucrose. Finally, in PIT tested rats, enhanced FOS immunoreactivity was revealed following the antagonist in regions thought to underlie PIT; however, the antagonist had no effect on FOS immunoreactivity in CPF tested rats.