Division of Hypothalamic Research, Department of Internal Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9077, USA.
J Clin Invest. 2011 Jul;121(7):2684-92. doi: 10.1172/JCI57660. Epub 2011 Jun 23.
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.
大众媒体和个人轶事都充满了压力诱发的高热量“舒适食物”摄入的例子。这种行为反应可能导致经历慢性应激或非典型抑郁的肥胖症患者的患病率增加。然而，控制应激诱导进食的复杂行为的分子基础和神经回路在很大程度上仍然未知，并且很少有动物模型被描述用于探究协调这种反应的机制。在这里，我们描述了一种系统，其中使用条件性位置偏好 (CPP) 任务评估食物奖励行为，在慢性社交挫败应激 (CSDS) 后监测小鼠，CSDS 是一种长期心理社会应激模型，具有重度抑郁症和创伤后应激障碍的某些方面。在这种情况下，CSDS 增加了 CPP 和高脂肪饮食的摄入量，应激诱导的食物奖励行为依赖于肽激素胃饥饿素的信号。此外，儿茶酚胺能神经元的信号传导不仅介导了胃饥饿素的食欲、抗抑郁样和食物奖励行为效应，而且足以介导应激诱导的食物奖励行为。因此，这种小鼠模型使我们能够将与胃饥饿素相关的儿茶酚胺能神经元在应激诱导的进食中的作用归因于它们。
