Assessing the effects of stress on feeding behaviors in laboratory mice.
Assessing the effects of stress on feeding behaviors in laboratory mice.
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评估压力对实验室小鼠喂养行为的影响。
DOI：
10.7554/elife.70271
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发表时间：
2022-02-15
期刊：
影响因子：
7.7
通讯作者：
Zeltser L
中科院分区：
文献类型：
--
作者：
Francois M;Canal Delgado I;Shargorodsky N;Leu CS;Zeltser L
压力通常会影响饮食行为，增加一些人的热量摄入，减少另一些人的热量摄入。进食对压力的反应的决定因素是未知的，部分原因是这个问题很少在啮齿动物中研究。我们把精力集中在新奇抑制进食（NSF）试验上，该试验使用进食的潜伏期作为焦虑样行为的读数，但很少评估进食本身。我们探讨了实验范式中的关键变量-发情和昼夜周期性，社会隔离的年龄和持续时间，膳食状态，饮食适口性和体重升高-如何影响雄性和雌性C57 BL/6 J小鼠的应激诱导的焦虑样行为和食物摄入。在大多数测试条件下，两性在新环境中进食的潜伏期都有所增加，而对热量摄入的影响是可变的。在常见的NSF测定中（即，瘦小鼠在光周期），性别特异性的影响，社会隔离的长度，而不是发情周期，是变异的主要来源。在与人类更生理相关的条件下（即，处于活动期的超重小鼠），这种新型压力现在会引起男女两性强烈的食欲过盛。这种新的应激进食模型可用于识别潜在的神经内分泌和神经元底物。此外，这些研究可以作为一个框架，整合跨学科的研究焦虑和摄食相关行为的啮齿动物。在焦虑加剧的时候--比如在全球大流行期间--我们中的许多人会伸手去拿甜甜圈或一个特别开胃的披萨来安慰自己。然而，其他人会倾向于避开食物。这些差异背后的原因是什么，事实上，在压力饮食（当人们由于情绪原因而不饿时）中起作用的神经和激素通路仍然不清楚。这部分是因为科学家缺乏良好的动物模型来研究这些行为。特别是，雌性啮齿动物通常被排除在研究之外，假设它们的激素周期会破坏结果。然而，在关于饮食习惯的研究中，妇女所占比例过高。用啮齿动物来模拟人类行为比看起来要困难得多。这些动物在晚上最活跃，但大多数实验都是在白天进行的。同样的压力源在男性和女性中也有不同的结果。因此，François等人探索了更好的方法来诱导焦虑和评估小鼠的进食行为，希望能可靠地引发应激性进食。研究的起点是一种常见的实验类型，称为新奇抑制喂养。首先，将小鼠单独关在笼子里长达两周，吃正常饮食，以便它们适应实验条件。然后，他们被剥夺了食物过夜，然后在一个新的环境中免费获得食物。这种紧张的经历通常会导致老鼠比在笼子里吃东西的时间更长。在啮齿类动物中，这种延迟被认为反映了压力，因为它可以被批准用于人类的抗焦虑化合物可靠地逆转。在新奇性抑制摄食试验中，雄性和雌性动物都表现出焦虑的迹象，但雌性动物吃多少是可变的。弗朗索瓦等人表明，这种变异性不是由于激素变化，而是由于雌性小鼠单独饲养的时间长短。至关重要的是，可以对测试进行调整，使小鼠始终表现出类似于人类应激进食的行为，即在测试期间吃得更多，而前一天晚上没有禁食。这些变化包括在动物通常最活跃的晚上进行实验，并使用超重的小鼠（这捕捉到了这样一个事实，即在人类中，超重与容易因压力而进食有关）。压力饮食是一个重要的临床问题，阻碍了肥胖症患者的体重减轻。弗朗索瓦等人开发的新模型可以被其他实验室采用，从而更好地研究这种行为。
Stress often affects eating behaviors, increasing caloric intake in some individuals and decreasing it in others. The determinants of feeding responses to stress are unknown, in part because this issue is rarely studied in rodents. We focused our efforts on the novelty-suppressed feeding (NSF) assay, which uses latency to eat as readout of anxiety-like behavior, but rarely assesses feeding per se. We explored how key variables in experimental paradigms – estrous and diurnal cyclicity, age and duration of social isolation, prandial state, diet palatability, and elevated body weight – influence stress-induced anxiety-like behavior and food intake in male and female C57BL/6J mice. Latency to eat in the novel environment is increased in both sexes across most of the conditions tested, while effects on caloric intake are variable. In the common NSF assay (i.e., lean mice in the light cycle), sex-specific effects of the length of social isolation, and not estrous cyclicity, are the main source of variability. Under conditions that are more physiologically relevant for humans (i.e., overweight mice in the active phase), the novel stress now elicits robust hyperphagia in both sexes . This novel model of stress eating can be used to identify underlying neuroendocrine and neuronal substrates. Moreover, these studies can serve as a framework to integrate cross-disciplinary studies of anxiety and feeding related behaviors in rodents. In times of heightened anxiety – say, during a global pandemic – many of us will reach for donuts or a particularly appetizing pizza for comfort. Others, however, will tend to shun food. What underlies these differences, and, in fact, the neural and hormonal pathways at play during stress eating (when people eat without being hungry due to emotional reasons), remain unclear. This is partly because scientists lack good animal models in which to study these behaviors. In particular, female rodents are usually excluded from studies under the assumption that their hormonal cycles will disrupt the results. Yet, women are overrepresented in studies on feeding habits. Modeling human behaviors using rodents is harder than it may appear. These animals are most active at night – yet most experiments are performed during the day. The same stressors also have different outcomes in males and females. François et al. therefore explored better ways to induce anxiety and evaluate feeding behavior in mice, hoping to reliably elicit stress eating. The starting point was a common type of experiments known as novelty-suppressed feeding. First, mice are kept alone in a cage for up to two weeks on a normal diet so that they are used to experimental conditions. Then they are deprived of food overnight, before being given free access to food in the morning in a new environment. This stressful experience normally causes mice to take longer to eat than in their home cage. In rodents, the delay is thought to reflect stress as it is reliably reversed by anti-anxiety compounds approved for human use. In the novelty-suppressed feeding assay, both male and female animals exhibit signs of anxiety, but how much females eat is variable. François et al. showed that this variability is not due to hormonal changes, but instead to how long female mice had been kept alone. Crucially, the test could be adapted so that mice would consistently exhibit behavior similar to human stress eating, whereby they eat more during the test without having fasted the night before. The changes included running the experiment at night, when the animals are normally most active, and using overweight mice (which captures the fact that, in humans, being overweight is associated with being prone to stress eating). Stress eating is an important clinical issue, hindering weigh loss in people with obesity. The new model developed by François et al. could be adopted by other laboratories, enabling better research into this behavior.