Ghrelin mediates stress-induced food-reward behavior in mice
Ghrelin mediates stress-induced food-reward behavior in mice
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DOI：
10.1172/jci57660
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发表时间：
2011-07-01
影响因子：
15.9
通讯作者：
Zigman, Jeffrey M.
中科院分区：
文献类型：
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作者：
Chuang, Jen-Chieh;Perello, Mario;Zigman, Jeffrey M.
大众媒体和个人轶事中充斥着因压力而吃高热量“舒适食品”的例子。这种行为反应可能会导致在经历慢性压力或非典型抑郁症的人类中肥胖率增加。然而，控制基于压力进食的复杂行为的分子底物和神经回路仍然大多未知，也很少有动物模型被描述来探索这种反应的机制。在这里，我们描述了一个系统，在这个系统中，通过条件位置偏好(CPP)任务评估的食物奖励行为，在暴露于慢性社会失败应激(CSDS)后对小鼠进行监测。慢性社会失败应激是一种长期心理社会应激的模型，具有严重抑郁和创伤后应激障碍的特征。在这种机制下，CSDS增加了高脂饮食的CPP和摄入量，压力诱导的食物奖励行为依赖于多肽激素Ghrelin的信号传递。此外，儿茶酚胺能神经元中的特异性信号不仅介导了ghrelin的食欲性、抗抑郁样和食物奖赏行为效应，而且足以介导应激诱导的食物奖赏行为。因此，这个小鼠模型允许我们将Ghrelin参与的儿茶酚胺能神经元在应激诱导进食中的作用归因于此。
The popular media and personal anecdotes are rich with examples of stress-induced eating of calorically dense "comfort foods." Such behavioral reactions likely contribute to the increased prevalence of obesity in humans experiencing chronic stress or atypical depression. However, the molecular substrates and neurocircuits controlling the complex behaviors responsible for stress-based eating remain mostly unknown, and few animal models have been described for probing the mechanisms orchestrating this response. Here, we describe a system in which food-reward behavior, assessed using a conditioned place preference (CPP) task, is monitored in mice after exposure to chronic social defeat stress (CSDS), a model of prolonged psychosocial stress, featuring aspects of major depression and posttraumatic stress disorder. Under this regime, CSDS increased both CPP for and intake of high-fat diet, and stress-induced food-reward behavior was dependent on signaling by the peptide hormone ghrelin. Also, signaling specifically in catecholaminergic neurons mediated not only ghrelin's orexigenic, antidepressant-like, and food-reward behavioral effects, but also was sufficient to mediate stress-induced food-reward behavior. Thus, this mouse model has allowed us to ascribe a role for ghrelin-engaged catecholaminergic neurons in stress-induced eating.