V-114 / oral | Role of Agouti-related protein-expressing neurons and growth hormone secretagogue receptor in reward-related behaviors under calorie restriction

Neuroendocrinology and Neuroimmunology
Author: Daniela Alejandra Cassano | Email: danicassano@hotmail.com

Daniela Alejandra Cassano^1°, Franco Barrile^1°,Mirta Reynaldo^1°, Nathalia Ferreira^2°, María Paula Cornejo^1°, Higor Fideles Silva^2°, Rodrigo Rorato^2°, Helgi Schioth^3°, Mario Perelló^1°3°

^1° Laboratory of Neurophysiology of the Multidisciplinary Institute of Cell Biology (IMBICE) (CONICET – CICPBA – UNLP). La Plata, Argentina
^2° Department of Biophysics, Paulista Medical School, Federal University of Sao Paulo. São Paulo, Brasil
^3° Department of Surgical Sciences, Functional Pharmacology and Neuroscience, University of Uppsala. Uppsala, Sweden

Ghrelin is a stomach-derived hormone that acts via growth hormone secretagogue receptor (GHSR). GHSR has ligand dependent and independent actions and is highly expressed in Agouti-related protein (AgRP) expressing neurons located in the hypothalamic arcuate nucleus (ARH). Ghrelin rises during energy deficit condition, and leads to the activation of AgRP neurons. GHSR signalling and AgRP neurons are known to modulate reward-related behaviors. We studied the role of AgRP neurons and GHSR in the enhancement of reward-related behaviours in calorie-restricted (CR) mice. Male mice were fed with the 40% of their daily food intake for 5 days and daily exposed to a non-caloric sweetener solution, saccharine, for 4 hours before each meal. We characterized the ghrelin-GHSR system and we found that CR wildtype mice showed an increase in GHSR mRNA levels in the ARH, an increase in plasma ghrelin levels and an increase of saccharine intake. Using two transgenic mouse model with lack of GHSR or a reduction of GHSR ligand independent activity we found that GHSR is required for the enhancement of reward-related behavior. Using DREADDs technology we, 1) selectively inhibited AgRP neurons and found a reduction of CR-induced enhancement of saccharine intake, and 2) selectively activated AgRP neurons in ad libitum fed mice and found an increase of saccharin intake. In conclusion, GHSR expression and activation of AgRP neurons are required for the enhanced saccharine intake during CR.