Nucleus accumbens opioids promote approach to high-fat rewards in the absence of caloric need

Abstract

When relatively sated, people are still easily tempted to consume calorie-dense foods, particularly those containing fat and sugar, and consumption of such foods while calorically replete likely contributes to obesity. The nucleus accumbens (NAc) opioid system has long been viewed as a critical substrate for this behavior, mainly via contributions to the neural control of consummatory behavior and palatability. This is chiefly due to observations that stimulation of NAc μ-opioid receptors (MORs) selectively enhances the consumption of palatable food and increases hedonic taste reactions to such food. This view is incomplete, however, due to the observation that blockade of NAc MORs does not consistently reduce consumption. Further, stimulation of NAc MORs increases certain measures of appetitive behavior, suggesting that NAc MOR activation may directly promote food seeking. Therefore, we hypothesized that when people or animals are sated, their preferences shift toward palatable food because endogenous ligands of NAc MORs selectively promote seeking of calorie-dense foods. To test this hypothesis, we trained rats on a conditioned stimulus task that disambiguates appetitive and consummatory behavior. In this task, rats perform an approach response to a reward-predictive cue to obtain a highly palatable, calorie-dense liquid food (cream). By simultaneously recording from NAc neurons and injecting a MOR antagonist into the NAc, we demonstrate that NAc MOR activation is required for both behavioral responding to reward-predictive cues and for the neural encoding of those cues by NAc neurons, which are thought to drive approach behaviors. Importantly, these effects were observed in ad libitum chow-fed rats but not in those that had been food restricted. This striking dichotomy indicates that activation of NAc MORs promotes the approach to palatable food only in the absence of a homeostatic need for calories – i.e., hunger – suggesting a novel mechanism that drives intake of calorie-dense food specifically in the state of satiety.