Ghrelin signaling is not essential for sugar or fat conditioned flavor preferences in mice

•Flavor preferences are conditioned by sugar and fat in mice.•Ghrelin signaling is implicated in food reward processing.•Ghrelin receptor-deficient mice displayed normal flavor conditioning.•Ghrelin receptor antagonism did not block sugar-conditioned flavor preferences.•Ghrelin signaling is not essential for sugar or fat conditioned flavor preferences.

The oral and post-oral actions of sugar and fat stimulate intake and condition flavor preferences in rodents through a process referred to as appetition. Ghrelin is implicated in food reward processing, and this study investigated its involvement in nutrient conditioning in mice. In Exp. 1 ghrelin receptor-null (GHSR-null) and C57BL/6 wildtype (WT) mice learned to prefer a flavor (CS+) mixed into 8% glucose over another flavor (CS−) mixed into a “sweeter” but non-nutritive 0.1% sucralose + saccharin (S + S) solution. In Exp. 2 treating WT mice with a ghrelin receptor antagonist [(D-Lys3)-GHRP-6] during flavor training did not prevent them from learning to prefer the CS+ glucose over the CS− S + S flavor. GHSR-null and WT mice were trained in Exp. 3 to drink a CS+ paired with intragastric (IG) infusion of 16% glucose and a CS− paired with IG water. Both groups drank more CS+ than CS− in training and preferred the CS+ to CS− in a choice test. The same (Exp. 4) and new (Exp. 5) GHSR-null and WT mice learned to prefer a CS+ flavor paired with IG fat (Intralipid) over a CS− flavor paired with IG water. GHSR-null and WT mice also learned to prefer a CS+ flavor added to 8% fructose over a CS− added to water. Together, these results indicate that ghrelin receptor signaling is not required for flavor preferences conditioned by the oral or post-oral actions of sugar and fat. This contrasts with other findings implicating ghrelin signaling in food reward processing and food-conditioned place preferences.