CONICET | Buscador de Institutos y Recursos Humanos

Ghrelin is a hormone relevant in the context of eating disorders, as it promotes food intake during fasting and stimulates the consumption of palatable foods in satiated states. Strikingly, ghrelin receptor, the growth hormone secretagogue receptor (GHSR), signals in the presence and in the absence (constitutive activity) of ghrelin. GHSR is expressed in dopamine neurons of the ventral tegmental area (VTA), a key nucleus of the mesolimbic pathway involved in processing rewarding experiences, such as the consumption of palatable foods. Ghrelin administration to humans activates brain nuclei involved in reward processing, and intra-VTA administration of ghrelin in rodents increases, while GHSR blockage decreases, the intake of and the motivation to obtain palatable foods1. Ghrelin treatment in mice modulates VTA dopamine and GABA neurons activity2. To understand the role of GHSR in the mesolimbic pathway and its regulation of high-fat (HF) food intake, we have developed a binge-like eating protocol, in which mice are daily and time-limited exposed to a HF diet. We found that wild-type (WT) mice escalate HF diet intake over days and display an activation of the mesolimbic circuit, while GHSR-deficient mice exposed to the binge-like eating protocol eat less HF diet and show no activation of the mesolimbic pathway3. We also found that blocking constitutive, but not ghrelin-evoked GHSR activity abolishes the escalating profile and reduces HF diet intake in the binge-like eating protocol4. Recently, we also showed that GHSR expression exclusively in dopamine neurons is sufficient to restore specific appetitive and consummatory behaviors towards HF diet5. Thus, our studies show that ghrelin-independent GHSR actions in the mesolimbic pathway regulates reward-related behaviors towards HF diet.