Hedonic and incentive signals for body weight control

Abstract

Here we review the emerging neurobiological understanding of the role of the brain's reward system in the regulation of body weight in health and in disease. Common obesity is characterized by the over-consumption of palatable/rewarding foods, reflecting an imbalance in the relative importance of hedonic versus homeostatic signals. The popular 'incentive salience theory' of food reward recognises not only a hedonic/pleasure component ('liking') but also an incentive motivation component ('wanting' or 'reward-seeking'). Central to the neurobiology of the reward mechanism is the mesoaccumbal dopamine system that confers incentive motivation not only for natural rewards such as food but also by artificial rewards (eg. addictive drugs). Indeed, this mesoaccumbal dopamine system receives and integrates information about the incentive (rewarding) value of foods with information about metabolic status. Problematic over-eating likely reflects a changing balance in the control exerted by hypothalamic versus reward circuits and/or it could reflect an allostatic shift in the hedonic set point for food reward. Certainly, for obesity to prevail, metabolic satiety signals such as leptin and insulin fail to regain control of appetitive brain networks, including those involved in food reward. On the other hand, metabolic control could reflect increased signalling by the stomach-derived orexigenic hormone, ghrelin. We have shown that ghrelin activates the mesoaccumbal dopamine system and that central ghrelin signalling is required for reward from both chemical drugs (eg alcohol) and also from palatable food. Future therapies for problematic over-eating and obesity may include drugs that interfere with incentive motivation, such as ghrelin antagonists.

Fig. 1

Schematic illustration of the interactions of between homeostatic/metabolic and hedonic control of food intake in normal weight and obese individuals. Palatable foods reinforce their consumption by increasing both the motivational and hedonic components of the reward process. Whereas homeostatic signals are able to put a brake on food reinforcement in normal weight individuals, this does not appear to be the case for the obese. Moreover, increased food intake in obesity may reflect an allostatic shift in the set-point for food reward, characterized by either an increased hedonic requirement (the reward hyperfunction theory) or an increased motivation to compensate for a hedonic deficit (the reward hypofunction theory). By analogy with chemical drug addiction, problematic over-eating may commence with an increased hedonic requirement but with increased exposure, the hedonic/rewarding value of the food decreases, resulting in an increased motivation for food (ie eating in the absence of pleasure in the ‘food addicted’ state). Unfortunately obesity- associated leptin and insulin resistance likely play an important role to desynchronize these appetitive brain mechanisms. Recent studies have identified the central ghrelin signalling system as having an important role for increasing food reward. Given that obese individuals appear to remain ghrelin sensitive, future therapies for problematic overeating could include ghrelin antagonists

Fig. 2

Central ghrelin signalling is required for the incentive motivation (“wanting”) for sweet rewards in rats. Operant responding (lever-pressing) for a sucrose reward is a increased by peripheral administration of ghrelin to satiated rats and b decreased by peripheral administration of a GHS-R1A (ghrelin receptor) antagonist to hungry rats. Reproduced with permission from Addiction Biology (122)