Ghrelin receptor signaling in dopamine neurons mediates high fat intake in a binge eating model

CORNEJO MP, BARRILE F, GARCÍA ROMERO G, CASSANO D, TOLOSA MJ, REYNALDO M, ANDREOLI MF, PERELLO M.

Daegu

Congreso; 10th IBRO WORD CONGRESS OF NEUROSCIENCE; 2019

IBRO

Ghrelin is a peptidic hormone secreted by specialized endocrine cells located in the stomach fundus. It regulates a variety of biological processes, including energy homeostasis. Ghrelin administration to humans and rodents induces food intake. The regulation of eating exerted by ghrelin is mainly due to its action in the brain, where different neuronal populations express ghrelin receptor, the growth hormone secretagogue receptor (GHSR). Among the populations of neurons that express the GHSR are the dopaminergic neurons. In this study, we investigated the role of dopaminergic GHSR-expressing neurons in the regulation of ghrelin?s biological effects. We employed a genetically modified mouse model in which Cre recombinase is expressed exclusively in dopaminergic neurons (DAT-Cre mice). We crossed DAT-Cre mice to a mouse model in which GHSR expression is blocked by a LoxP-flanked transcription blocking cassette (GHSR-deficient mice) in order to generate mice expressing GHSR selectively in dopaminergic neurons (GHSR-deficient/DAT-Cre mice). We first tested if the GHSR-deficient/DAT-Cre mice were a useful tool to study the effect of GHSR expression exclusively in dopaminergic neurons. Then, we studied the effect of peripheral ghrelin administration to GHSR-deficient/DAT-Cre mice. We also studied the effect of central ghrelin administration in the locomotor activity and food intake of GHSR-deficient/DAT-Cre mice. Finally, we employed different behavioral tests, including a binge eating and a conditioned place preference protocol, in order to determine the role of dopaminergic GHSR-expressing neurons in the regulation of ingestive behaviors. Our results indicate that ghrelin receptor signaling in dopaminergic neurons mediates complex feeding behaviors while the selective expression of GHSR in dopaminergic neurons is not sufficient to restore ghrelin-induced food intake and locomotor activity.