| Interactions between neural stress and reward pathways underlie a number of modern health problems, including substance abuse and overeating. This work was designed to elucidate the mechanisms by which stress and reward influence palatable diet consumption, and how interactions between these systems contribute to behaviors related to food intake and preference. We utilized genetic models of heightened stress and reward sensitivity as well as environmental models of high fat diet withdrawal and early life exposure to investigate the effects of a natural reward, high fat diet, on neural pathways and behavior. Using a genetic model of increased stress sensitivity, we found that chronic variable stress leads to an increased preference for a high fat diet and an increased risk for binge-type eating. We built upon this study by showing that when access to a previously consumed high fat diet is removed, mice exhibit signs of increased emotionality and stress and decreased reward signaling. These changes are associated with an increased motivation to consume high fat diet in our dietary reinstatement paradigm. In subsequent mechanistic studies using a genetic model of increased reward sensitivity, we found evidence that increased motivation for reward is associated with reduced markers of basal dopamine signaling, and that consumption of a high fat diet ameliorates these deficits. We have shown that an increased vulnerability to dietary reinstatement persists for 4-6 weeks following diet withdrawal and is associated with changes in stress and reward signaling. Finally, in our early exposure model, we demonstrated that exposure to a high fat during early life leads to changes in gene expression in reward systems that persist for months following diet exposure and are associated with an increased preference for high fat diet. This work demonstrates the powerful effects of a natural reward, high fat diet, on stress and reward systems in the brain, and suggests possible therapeutic strategies designed to reduce stress and elevate brain dopamine levels in order to reduce the risk of relapse to high fat diet consumption. |
