GLP-1 receptor agonist exenatide uncouples food intake from hedonic and anticipatory regulation in non-human primates: Insights from an operant meal schedule paradigm

Glucagon-like peptide 1 (GLP-1), a neuroendocrine signal of energy balance and satiety, has a major role in regulating food intake behaviour. Here we investigated the effects of the GLP-1 agonist exenatide on palatability-driven feeding regulation in adult male rhesus macaques (n=5) using a novel operant food intake paradigm with four meal schedule conditions where two types of pellets with different palatability values were offered as meal in all combinations in two consecutive daily feeding sessions (S1 and S2). In control conditions, a strong, palatability-driven anticipatory effect was found in S1, followed by a complementary positive contrast effect in S2. After acute subcutaneous treatment with 1 µg/kg dose of exenatide 1 h before S1, food intake decreased to the same very low level in all meal schedule conditions in S1, completely erasing the previously observed anticipatory effect. Conversely, exenatide induced hypoglycaemia in an anticipatory meal schedule dependent pattern. Interestingly, the previously observed positive contrast effect was spared in S2, with a weaker residual effect specifically on the consumption of the more palatable pellet type. To conclude, the food intake reducing effects of exenatide may temporally evolve from strong anorectic to weak anhedonic modulations, where hedonic experience and anticipation during the early anorectic phase is conserved but uncoupled from food intake behaviour.