Dopaminergic enhancement of local food-seeking is under global homeostatic control

Recent work has implicated dopaminergic mechanisms in overeating and obesity with some researchers suggesting parallels between the dopamine dysregulation associated with addiction and an analogous dysregulation in obesity. The precise role of dopamine in mediating reward and reinforcement, however, remains controversial. In contrast to drugs of abuse, pursuit of a natural reward, such as food, is regulated by homeostatic processes that putatively maintain a stable energy balance keeping unrestrained consumption and reward pursuit in check. Understanding how the reward system is constrained by or escapes homeostatic regulation is a critical question. The widespread use of food restriction to motivate animal subjects in behavior paradigms precludes investigation of this relationship as the homeostatic system is locked into deficit mode. In the present study, we examined the role of dopamine in modulating adaptive feeding behavior in semi-naturalistic homecage paradigms where mice earn all of their food from lever pressing. We compared consumption and meal patterning between hyperdopaminergic dopamine transporter knock-down and wild-type mice in two paradigms that introduce escalating costs for procuring food. We found that hyperdopaminergic mice exhibited similar demand elasticity, weight loss and energy balance in response to cost. However, the dopamine transporter knock-down mice showed clear differences in meal patterning. Consistent with expectations of enhanced motivation, elevated dopamine increased the meal size and reduced intrameal cost sensitivity. Nonetheless, this did not alter the overall energy balance. We conclude that elevated dopamine enhances the incentive or willingness to work locally within meals without shifting the energy balance, enhancing global food-seeking or generating an energy surplus.