An ethological perspective on the role of dopamine in feeding behavior and energy balance

The function of the dopamine system in generating appetitive behaviors is hotly debated, with several competing heuristics derived from human psychology fueling experimental approaches. These heuristics explain how dopamine manipulations affect behavior by making anthropomorphic assumptions about: (1) an animal's subjective experiences of hedonia, (2) the animal's thought process as behaviors become more routine, and (3) the value an animal assigns to reinforcers and cues that precede them. However, the ethological behaviorist perspective is that we cannot know with any scientific certainty what an animal subject is thinking or feeling. Ethological approaches are rooted firmly in neuroanatomical and physiological mechanisms and do not use human psychological phenomena to explain animal behavior. Ethological experiments also make use of more naturalistic testing environments, whereas traditional comparative psychology approaches tend to study behavior in relatively artificial paradigms.;Recent studies suggest that obesity is associated with dopamine signaling deficiencies in rodents and the human psychology heuristics have been employed to explain these phenomena. With an ethological approach in mind, I tested whether elevating dopamine tone in obese, leptin-deficient mice can reduce obesity. I found that hyperdopaminergic tone normalized food intake and rearing behavior, and increased general locomotor activity behavior in obese mice in environments where food was freely-available. These data suggest that dopamine can shift obese animals from a state of behavioral energy conservation to a state of behavioral energy expenditure. I developed a mechanistic model based on neuroanatomical and physiological evidence to explain this phenomenon.;Next I developed a naturalistic operant paradigm in which animals work for all of their food in their homecage via lever-pressing---an environment termed "closed economy," in which no artificial food-restriction is used to motivate food-seeking. I examined feeding behavior in obese, leptin-deficient mice and found that these mice lever-press more and eat more when the cost of food is low, but lever-press less, consume less, and become hypoactive relative to control mice as the cost increases and food becomes scarce. These data suggest that obese mice use behavioral energy conservation strategies to deal with food scarcity. Increasing dopamine production via L-dopa injections enhanced food-seeking within a meal in obese mice, suggesting that dopamine shifted obese animals to a state of behavioral energy expenditure in environments where food was scarce. Interestingly, leptin replacement also shifted obese mice to a state of behavioral energy expenditure as food became scarce, but their activity was directed away from food acquisition. These data suggest that leptin has distinct developmental vs. activational effects on the expression of behavioral expenditure vs. conservation strategies in adulthood. To test this hypothesis, I treated mice with leptin from postnatal day 5--12, when an endogenous surge in leptin is known to occur. I found that leptin surge-treated obese mice displayed a modest shift toward behavioral energy expenditure strategies in adulthood when tested in traditional operant paradigms using experimenter-induced food scarcity. Taken together, these data suggest that the postnatal leptin surge may program the use of behavioral energy expenditure strategies in adulthood. Future studies examining the role of the leptin surge in dopamine system development will establish whether the dopamine system is involved in this shift.