Metabolic sensing in AgRP regulates sucrose preference and dopamine release in the nucleus accumbens

Hunger increases the motivation for calorie consumption, often at the expense of low-taste appeal. However, the neural mechanisms integrating calorie-sensing with increased motivation for calorie consumption remain unknown. Agouti-related peptide (AgRP) neurons in the arcuate nucleus of the hypothalamus sense hunger, and the ingestion of caloric solutions promotes dopamine release in the absence of sweet taste perception. Therefore, we hypothesised that metabolic-sensing of hunger by AgRP neurons would be essential to promote dopamine release in the nucleus accumbens in response to caloric, but not non-caloric solutions. Moreover, we examined whether metabolic sensing in AgRP neurons affected taste preference for bitter solutions under conditions of energy need. Here we show that impaired metabolic sensing in AgRP neurons attenuated nucleus accumbens dopamine release in response to sucrose, but not saccharin, consumption. Furthermore, metabolic sensing in AgRP neurons was essential to distinguish nucleus accumbens dopamine response to sucrose consumption when compared with saccharin. Under conditions of hunger, metabolic sensing in AgRP neurons increased the preference for sucrose solutions laced with the bitter tastant, quinine, to ensure calorie consumption, whereas mice with impaired metabolic sensing in AgRP neurons maintained a strong aversion to sucrose/quinine solutions despite ongoing hunger. In conclusion, we demonstrate normal metabolic sensing in AgRP neurons drives the preference for calorie consumption, primarily when needed, by engaging dopamine release in the nucleus accumbens. Although hunger increases calorie intake independent from taste, the exact mechanisms through which this occurs remain unknown. This study shows that hunger-sensing neurons in the hypothalamus (AgRP neurons) are required to transmit hunger signals to dopamine release in the nucleus accumbens and drive the consumption of caloric solutions over non-caloric solutions. The ability of AgRP neurons to sense caloric need during fasting also prioritises calorie consumption over taste, a strong selective advantage when faced with unpleasant tastes. A greater appreciation of how hunger and motivation pathways interact is essential to understand dysfunctional conditions, such as under and overeating, which reflect human conditions such as eating disorders and/or obesity. image