Functional organization of brain reward circuitry

节食者能保持来之不易的减肥效果是很罕见的。由于人们对食物的兴趣增强，以及在餐桌上实行克制的难度增加，能量摄入量往往会反弹。与代谢率降低等生理变化相一致，这些行为调整有助于将体重推向其调节值。当实验室大鼠因食物供应限制而体重下降时，它们也会在恢复自由获取食物后，在促进体重增加的生理和行为方面进行多重调整。在他们对减肥的反应中，有一种是电刺激被称为穹隆周围下丘脑的大脑区域产生的奖励效应增加。通过按下杠杆，老鼠就会触发这一区域的刺激，它们愿意在减肥后为更低的“工资”(较弱的刺激)而工作。据认为，老鼠努力获得的奖励效应与囤积和觅食等与食物相关的行为有关。事实上，减肥会导致老鼠反复囤积大量食物，即使它们不被允许在之后保留食物或不吃大量食物。就像老鼠不知疲倦地工作以获得没有明显生理益处的大脑电刺激一样，它们会来回奔波数小时，以囤积它们无法保存的食物。这些活动似乎在本质上是有回报的，可能是因为它们如何利用共同的神经回路来评估、选择和获取具有生物学意义的资源。这项研究的目的之一是应用现代测量方法来探索穹隆周围下丘脑刺激、囤积和长期控制体重之间的关系。第二个目标是确定AMPK的持续激活是否在将脂肪储存与涉及奖励和囤积的大脑回路联系起来方面发挥作用。AMPK是一种分子燃料传感器，目前对能量平衡的研究非常感兴趣。通过解决这些问题，拟议的研究可能有助于解释减肥后食物和与食物相关的活动的价值是如何增加的。

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.