Calorie-restricted mice display activation of the reward-related brain centers and saccharine overconsumption, in a growth hormone secretagogue receptor-dependent manner

D. CASSANO, C. SAENZ, N. DE FRANSCESCO, G. FERNÁNDEZ, M. CORNEJO, G. GARCÍA ROMERO, M. PERELLÓ

Congreso; Neurosciencie 2021; 2021

Several evidences indicate that calorie restricted (CR) animals display short and long-term changes in their reward-related behaviors towards palatable stimuli, but the molecular basis underlying such adaptations remain uncertain. Ghrelin is a stomach-derived hormone that acts via growth hormone secretagogue receptor (GHSR) and enhances reward-related behaviors. GHSR is expressed in the ventral tegmental area (VTA), which is a hub of the so-called mesolimbic pathway that innervates the ventral striatum (i.g, the nucleus accumbens (Acb)) in order to control reward-related behaviors. Since plasma ghrelin levels increase under calorie restriction, GHSR signaling could act in the mesolimbic pathway and affect the short- and long-term behavioral adaptations toward rewarding stimuli observed in CR animals. Here, we investigated the induction of the marker of neuronal activation cFos 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. We observed that 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 where refed, we found that GHSR-deficient and WT mice did not show different hyperphagia, glycaemia or saccharine consumption, in a similar fashion as seen before the calorie restriction. Thus, we conclude that GHSR plays a main role during, but not after, a calorie restriction condition. In particular, we found GHSR seems to be required for the maintenance of energy balance and glucose homeostasis during calorie restriction as well as for the full calorie restriction-induced activation of the reward-related brain centers and saccharine overconsumption.