Functional organization of brain reward circuitry

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It is rare for a dieter to sustain a hard-won weight loss. Energy intake tends to rebound due to heightened interest in food and increased difficulty in exercising restraint at the table. In concert with physiological changes such as decreased metabolic rate, these behavioral adjustments help drive body weight back towards its regulated value. When laboratory rats lose weight due to restriction of their food supply, they also undergo multiple adjustments in physiology and behavior that promote weight gain after free access to food is restored. Among their responses to weight loss is an increase in the rewarding effect produced by electrical stimulation of a brain region called the perifornical hypothalamus. By pressing a lever, rats will work to trigger stimulation of this area, and they are willing to work for lower "wages" (weaker stimulation) after they have lost weight. It is thought that the rewarding effect the rats work to obtain is involved in food-related behaviors such as hoarding and foraging. Indeed, weight loss can induce rats to repeatedly hoard enormous quantities of food, even if they are not allowed to retain the food afterwards or do not eat significant quantities. Just as rats will labour tirelessly to obtain electrical brain stimulation of no obvious physiological benefit, they will scurry back and forth for hours to hoard food that they do not get to keep. These activities appear to be intrinsically rewarding, perhaps because of how they engage common neural circuitry involved in the evaluation, selection, and procurement of biologically significant resources. One objective of the proposed research is to apply modern measurement methods to probe the relationship among the rewarding effect of perifornical hypothalamic stimulation, hoarding, and the long-term control of body weight in rats. A second objective is to determine whether sustained activation of AMPK, a molecular fuel sensor that is the subject of intense interest in current research on energy balance, plays a role in linking fat stores to brain circuitry involved in reward and hoarding. By addressing these questions, the proposed research may help explain how the value of food and food-related activities increases following weight loss.