Glucose availability regulates ghrelin-induced food intake in the Ventral Tegmental Area.

Information about metabolic status arrives in the brain in the form of a complex milieu of circulating signalling factors including glucose and fatty acids, ghrelin, leptin and insulin. The specific interactions between humoral factors, brain sites of action and how they influence behaviour is largely unknown. We have previously seen interactions between glucose availability and the actions of ghrelin mediated via the AgRP neurons of the hypothalamus. Here we examine whether these effects generalise to another ghrelin-sensitive brain nucleus, the Ventral Tegmental Area (VTA). We altered glucose availability by injecting mice with glucose or 2-deoxyglucose (2-DG) ip to induce hyperglycaemia and glucopenia, respectively. 30 minutes later we injected ghrelin in the VTA. Glucose administration suppressed intra-VTA ghrelin-induced feeding. Leptin, a longer term signal of positive energy balance, did not affect intra-VTA ghrelin-induced feeding. 2-DG and ghrelin both increased food intake in their own right, and together they additively increased feeding. These results add support to the idea that calculation of metabolic need depends on multiple signals across multiple brain regions, and identifies that VTA circuits are sensitive to the integration of signals that reflect internal homeostatic state and influence food intake. This article is protected by copyright. All rights reserved.