Insulin and endocannabinoids in the mesolimbic system

Easy access to palatable food and an abundance of food-related cues exacerbate non-homeostatic feeding. The metabolic and economical sequelae of non-homeostatic feeding outweigh those of homeostatic feeding and contribute significantly to the global obesity pandemic. The mesolimbic dopamine system is the primary central circuit that governs the motivation to consume food. Insulin and endocannabinoids (eCBs) are two major, presumably opposing, players in regulating homeostatic and non-homeostatic feeding centrally and peripherally. Insulin is generally regarded as a postprandial satiety signal, whereas eCBs mainly function as pre-prandial orexinergic signals. In this review, we discuss the effects of insulin and eCB-mediated actions within the mesolimbic pathways. We propose that insulin and eCBs have regional- and time course-dependent roles. We discuss their mechanisms of actions in the ventral tegmental area and nucleus accumbens, as well as how their mechanisms converge to finely tune dopaminergic activity and food intake.