Growth hormone secretagogue receptor is required to enhance reward-related behaviors adaptations toward palatable stimuli in calorie-restricted mice

DANIELA CASSANO; CAMILA SAENZ; NICOLAS DE FRANCESCO; GIMENA FERNANDEZ

virtual

Congreso; SAN 2021 ANUAL MEETING; 2021

Sociedad Argentina de Neurociencias

Ghrelin is a stomach-derived hormone that acts via growth hormone secretagogue receptor (GHSR). GHSR is expressed in the mesolimbic pathway, especially in the ventral tegmental area (VTA) that innervates the nucleus accumbens (Acb). Since plasma ghrelin levels increase under calorie restriction, GHSR signaling could act in the mesolimbic pathway and affect reward-related behavioral adaptations. We investigate the cFos neuronal activation marker induction in the mesolimbic pathway as well as the saccharine consumption in wild-type (WT) mice and GHSR-deficient mice during a 5-day 60% calorie restriction protocol. GHSR-deficient mice showed: 1) a more severe weight loss and hypoglycemia, 2) a similar increase of cFos in the VTA but a smaller increase of cFos in the Acb, and 3) a reduced overconsumption of saccharin, than WT mice during the calorie restriction protocol. When CR mice were refed, we found that GHSR-deficient and WT mice did not show different hyperphagia or glycaemia but GHSR-deficient mice show reduced saccharine consumption as compared to WT mice. Thus, we conclude that GHSR plays a main role during, and after, a calorie restriction condition. In particular, we found GHSR seems to be required for the maintenance of energy balance and glucose homeostasis as well as for the full calorierestriction-induced activation of the reward-related brain centers and saccharine overconsumption during and after calorie restriction.