Functional organization of brain reward circuitry

节食者很难维持来之不易的减肥效果。能量摄入往往会反弹，因为对食物的兴趣增加了，在餐桌上克制自己的难度增加了。随着代谢率降低等生理变化，这些行为调整有助于将体重恢复到其调节值。当实验鼠因食物供应受限而体重减轻时，在恢复自由获取食物后，它们也会经历多种生理和行为调整，从而促进体重增加。在他们对减肥的反应中，电刺激下丘脑皮层周围区域所产生的奖励效应增加。通过按压杠杆，老鼠会努力触发该区域的刺激，并且它们愿意在减肥后为更低的“工资”（更弱的刺激）而工作。据认为，老鼠努力获得的奖励效应与食物相关的行为有关，如囤积和觅食。事实上，体重减轻会导致大鼠反复囤积大量食物，即使它们事后不被允许保留这些食物或不吃大量食物。就像老鼠会不知疲倦地工作以获得没有明显生理好处的脑电刺激一样，它们会跑来跑去几个小时来囤积它们无法保存的食物。这些活动似乎在本质上是有益的，也许是因为它们是如何参与评估、选择和获取重要生物资源的共同神经回路的。本研究的目的之一是应用现代测量方法探讨大鼠下丘脑皮层周围刺激的奖励效应、囤积与长期体重控制之间的关系。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，是当前能量平衡研究中非常感兴趣的主题。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有关的活动的价值如何增加。

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.