我们想感谢刘尚塔尔评估牛奶的摄入量，Klaus Miczek的社会压力使用的建议意见，和Sheryl古德曼的临床相关性慢性社会压力的反馈。支持此协议的发展BCN由NICHD K99/R00 HDO59943。

成年大鼠女性孕育在我们的动物设施，窝扑杀8-10幼仔与甚至性别比，孕产妇保健和侵略测试是在大鼠家笼。实验对象保持在同一房间内通过学习。妊娠第20天或21英寸高明确的有机玻璃制成的笼隔板放置在笼子里。这些划分成4个象限笼，防止仔兔从爬行回到大坝时，放置在笼子里。典型的母性行为确认所有水坝诞生的那一天（第1天哺乳期）通过直接观察小狗检索，修饰，护理，自我疏导。入侵者男性小于或同样大小的大鼠，男性和女性都从未提出过两次相同的男性。孕产妇保健和孕产妇侵略视频记录2，第9天早上，哺乳期和16，如下所述: <ol><li>从水坝中取出的垃圾，权衡男性和女性本身parately地方整个窝在一个干净的控股笼60分钟。 </li><li>在结束60分钟的分离，权衡男性和女性的幼崽分开之前更换窝在家里笼坝，将幼崽之间尽可能均匀3个非巢象限笼。放归前开始录像，以确保所有的小狗检索记录。 </li><li>视频记录孕产妇保健30分钟。允许水坝90分钟凋落物交互。 120分钟（30分钟录音+额外90分钟）后，将幼崽大坝的笼子，称他们再次确定牛奶的摄入量超过两小时内。一小狗被安乐死，每胎产仔行为测试天抽取牛奶样品从胃的120分钟，哺乳期的。从幼崽收集牛奶的目的是评估水平的激素和其他因素，可能调解慢性社会压力对后代的行为和/或生理效应。 </LI&gt; <li>大坝后返回幼仔体重，并引进30分钟测试产妇侵略腾笼换一个较小的或同样大小的新型男性入侵者。期间引进开始录像，以确保所有的侵略记录。对照组中，男性被删除后的30分钟录音。对于慢性社会压力科目，男性留在另一个30分钟。在非行为的测试天数在2-16天期间，新颖的入侵者男性被放置在笼子里的CSS科目无视频录制一小时。社会压力风险停止，如果发生伤害，受伤的动物的研究处理和删除。 </li><li>一瓶0.02％糖精被添加到2天，9天，下午3点和16个交替的左侧和右侧之间的大坝家笼。下午3点白开水和糖精瓶称重，然后再上午8点，第二天早上来确定糖精喜好。 </li><li>小狗断奶23日，一个水坝重新安乐死在这一点上取得基础血浆样本，提取大脑中的基因表达分析的生理和行为相关的靶核。 </li></ol>产妇行为评分孕产妇保健的侵略行为得分从表1和表2中所描述的视频使用Odlog行为分析软件。键被分配到每一个行为，并按住按键，而每个行为进行记录这种行为的持续时间。频率为每个行为的关键笔划的总和。这个程序创建一个完整的数据文件的时间戳记五个第二箱和一个汇总表与总的频率和持续时间超过30分钟录音的定义的行为。产妇侵略和孕产妇保健打进产妇侵略视频，水坝母体的幼崽，而男性入侵者是在笼子里。 </P&gt; 不久之后将幼崽在笼中，大坝将检索每个小狗单独回巢。全面检索打进一次，当所有的幼仔在巢。虽然通常只打进了全面检索一次，有时梅开二度，如果水坝搬迁整个垃圾经过最初的全面检索到一个新的网站。筑巢材料时打进筑巢行为是由大坝与她的嘴或爪子操纵的。小狗梳理，包括由大坝与她的爪子舔小狗的皮毛或操纵。护理得分开始建坝后一直在一个固定的的蹲下或俯卧护理姿势10秒。这是为了让幼崽开始哺乳时间。嵌套，小狗疏导和护理，孕产妇保健总额加起来的时间，但可能会受到限制，疏导和护理重点对小狗导向行为。被定义为自我疏导大坝的操纵自己的皮草与她的嘴或爪子。活动期间打进ING任何自发活动不与先前定义的行为。 产妇的侵略攻击，咬，踢，和寄托。被定义为攻击入侵者男性拳击或解决。咬得分，大坝时使用她的牙齿上的入侵者，并锁定记录时，大坝拥有男性与她的四肢或身体。总侵略攻击，咬，踢，和寄托的总和。 统计产妇的行为，牛奶的摄入量，控制和CSS水坝和糖精偏好进行了比较每个泌乳日单尾t检验的CSS个别天的影响进行评估。 2天，9天，16泌乳，生长数据进行了比较单尾t检验重量（克），第2天或百分比增长相对第2天（9或16天体重/天2砝码质量× 100）。 OXT的mRNA水平正常化对三个联合housek的表达eeping基因，β-肌动蛋白，次黄嘌呤磷酸酶（HPRT）和甘油醛-3 - 磷酸脱氢酶（GAPDH）。个别t检验每个大​​脑区域在每个肽或受体相对OXT mRNA表达水平进行比较。所有结果以图形组均值+ SEM，统计显着性水平为P≤0.05。

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作者没有竞争经济利益。

从CSS范式所获得的数据是最有可能是在一个稳定的行为研究环境一致的和可重复的。有人认为，住房和饲养实验动物的一个组成部分，需要更仔细考虑在任何类型的研究，尤其是行为研究。住房和畜牧业的做法，可能会引入混淆包括:开始从供应商出货的怀孕母畜，在行为测试的时候，一天的日常行为测试，变异房间之间移动水坝水坝新颖的景点，声音或气味，过度曝光行为测试，缺乏或不一致的筑巢材料，差的日常照顾动物（ 如暴露在潮湿和弄脏被褥），不使用家笼。此外，哺乳期间的其他行为的测试（ 例如强迫游泳测试或高架十字迷宫）列入可能引入混淆。然而，使用一种新型的笼环境或其他急性应激可能是有用的，揭示行为上的差异并不明显，由于潜在的慢性应激，急性应激和行为之间的相互作用家笼测试。 目前描述的协议是有效的Sprague Dawley大鼠，但可能需要的其它菌株和物种的协议的修改。例如，幼仔必须受到保护，形成一道屏障，高度侵袭性​​龙埃文斯男性，以防止受伤。严重的社会压力管理的做法包括使用更小或同样大小的男性，具有了高强度的第2天坝，以确保失败和一贯顺从的行为在男性的男性的入侵者的第一相互作用。如果男性攻击了一窝，他们应该从研究中删除，因为它很可能，他们将攻击后续窝。一个选项为减少咄咄逼人男性的可能性是他们打败了较大的男性开始前的ST乌德。行为得分，大多数行为的频率和持续时间的记录和分析的行为是必要的，以提供一个完整的画面，和记录间隔较短或抽查使用，可能会导致在收集足够的数据，以全面测试假设。与以前使用拿下行为视频，可以实现彻底的和一致的训练得分手。 CSS模型的应用主要是测试电流和新颖的药物治疗产后抑郁和焦虑。这种模式的另外一个用途是共同的做法和程序，对孕产妇护理，如剖宫产出生，引产，各种哺乳时间表的影响进行调查。由于缺乏关于这一主题的研究，将是有价值的潜在影响哺乳压力进一步调查。虽然牛奶样品从水坝将是有益的，需要麻醉和外源性OXT在收集这些样本介绍几个行为和生理上的混淆，因此可能不利于同步行为分析研究压力的影响哺乳。与CSS模型跨代研究的潜力是很大的，这些调查可能还包括各种胁迫处理调查的成年子女之间潜在的相互作用早期的生活压力和应激暴露。 CSS模型的意义和相关的行为学和翻译相关的行为检测中心。据推测，目前的治疗抑郁和焦虑的有效性的缺乏是由于缺乏动物和人类研究动物行为之间的重叠。抑郁症和焦虑症的动物模型往往依靠强大的物理压力或高度选择的菌株，这也许可以解释发现，严重的抑郁症，目前的抗抑郁药治疗是最有效的。 PH<html>克制，接触到各种各样的随机应激压力，如ysical不模拟人类共同的经验。慢性轻度应激范式上使用随机曝光的理由是为了防止驯化。这是一个显着的关注，但理想的情况，可能是使用的协议动物不更接近于人类社会压力，如抑郁症和焦虑症的病因适应。除了推广使用更多的行为学压力，CSS模型的另一个优点是使用快感缺乏相关措施，产妇的行为。这是一个强大的奖励介导的行为直接介导抑郁症的不利影响，对后代的母亲。抑郁和焦虑研究行为学的压力和快感缺乏措施纳入合并将特别有利于识别安全和有效的预防措施和治疗。 "&gt;社会压力已经成功使用在男性和女性未产妇的几年，这项工作扩展到产妇的女性可能会产生产后抑郁症新颖的数据，以及丰富的早年生活压力相关的疾病在男性和女性。据推测，在抑郁和焦虑研究动物行为的动物模型使用量的增加将导致更有效的治疗由于是ethologically和翻译相关变量，并更具可重复性行为数据收集。

病因包括产后抑郁症，情绪障碍，往往涉及承受慢性应激1,2。虽然抑郁症的母亲有养育3和心理发展的后代4的负面影响，绝大多数研究雄性动物和人类的抑郁和焦虑的重点。虽然有几个产妇的行为改变慢性应激的动物模型，最有可能不会涉及到人类所经历的常见慢性心理压力主要集中在产前期间大量的生理成分。慢性应激大鼠在怀孕期间增加孕产妇保健和焦虑，降低产妇侵略，在一些研究中5，但在其他6降低孕产妇保健。应激是一种强效的物理应激7，有些报道是不符合人类MOT观察衰减孕产妇保健她与产后抑郁症4。产前ultramild应力不会影响小狗的照顾，但不会降低孕产妇的侵略8。的Ultramild应力范式使用各种随机的压力（如笼倾斜30度，扭转光周期，禁闭，夜间照明，脏笼子）了好几天了，各个组件的效果往往是不清楚的。一些压力，如在ultramild应力范式反相光周期和夜间照明很可能是独立于任何应力的影响，直接影响孕产妇保健，孕产妇保健大鼠昼夜节律。暴露于潮湿的床上用品是一个显着的热应力的幼崽，可导致幼鼠死亡在不到24小时在年轻的窝（个人意见）。 最近的啮齿类动物的研究一直专注于使用的的有关压力ethologically，如慢性社会压力（CSS），在取舍的压力的影响研究普林的行为和情绪障碍9-13。在努力发展产后抑郁症的动物行为学模型，减少生理组件使用的应激，并产生一致的行为和生理的结果，我们的实验室一直专注于利用社会压力。虽然慢性社会的失败被有效地用于社会压力引起的抑郁症，雄性啮齿动物14作为一种模式，这是许多产妇啮齿动物的生态环境相关的行为模型如果男性入侵者使用，作为一个单一的产妇的啮齿动物通常会导致社会的失败在自相残杀的垃圾男性入侵者。然而，急性暴露于一种新型男性入侵者，没有社会的失败的大坝，引发强大的行为和内分泌的应激反应，在哺乳期女性15-18。也有证据表明，在哺乳期的慢性应激，包括暴露于男性的入侵者，直接削弱牛奶生产19,20，这可能会影响小狗的增长。这些结果支持母鼠处女雌，其中慢性社会不稳定（不同的隔离和拥挤）增加11,21，改变体温调节下丘脑-垂体-肾上腺轴的活动，研究蔗糖和食物摄入量减少，并已提出11女性抑郁症的动物模型。自我疏导也是衡量焦虑22,23到社会压力操控24,25敏感。 产妇在哺乳期的慢性社会压力（CSS）可以破坏行为和削弱经济增长的大坝和后代。每天介绍一种新型的男性入侵者在哺乳期降低孕产妇保健，提高产妇的侵略对一种新型的男性的入侵者和自我疏导，并抑制增长大坝和她的后代10。这些作用表明，CSS是一种情绪障碍相关和有效的模型ethologically涉及在孕产妇保健，快感缺乏，焦虑升高，减毒后代的生长，如产后抑郁症的障碍。孕产妇保健和后代数据表明，CSS可能对后世产生持久的影响，慢性应激对产妇的行为的影响的研究支持这一假设激素介导的慢性应激对产妇的行为的影响（穆加特罗伊德和侄子2012 ）。此外，最近的数据从成年雌性后代强调水坝支持CSS早年生活压力的一种形式的假设导致中央催产素（OXT）和催乳素（PRL）这是与低效的护理行为12。 CSS模型补充其他有效的模型的应力引起的中断产妇的行为，如限制筑巢材料26,27和28,29母婴分离。 CSS模型的独特的方面是，它是ethologically在啮齿类动物和人类都有关，拥有一个相对较小的生理成分，并可以结合其他生命阶段的类似压力（社会溃败，慢性社会不稳定）。 在发展中国家的CSS范式的主要目标是使用ethologically和临床相关的压力源，引起快感缺乏（作为衡量孕产妇保健和糖精偏好），增加焦虑行为的措施，同时损害小狗的生理，行为和内分泌的发展。该模型的目的是测试当前和新的治疗方法和做法，产后抑郁和焦虑。

<table border="1">
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using chronic social stress to model postpartum depression in lactating rodents

暴露于慢性应激抑郁症是一个可靠的预测，并在动物和人类社会压力是一种常见ethologically相关的应激。然而，许多抑郁症动物模型的开发在男性和不适用或有效产后女性的研究。最近的研究报告哺乳期间，ethologically相关和有效的应激显着影响的慢性社会压力，对产妇的行为，生长和神经内分泌学。这份手稿将描述这种慢性社会压力范式的使用反复接触哺乳坝一种新型男性入侵者，并评估这个模型的行为，生理和神经内分泌的影响。慢性社会压力（CSS）是一个有价值的模型研究的大坝，以及她的后代和后代的行为和生理上的压力的影响。也可以用来作为一个早期曝光幼仔的CSS生活压力大，有长期的行为，生理，神经内分泌的影响。

公开哺乳坝的CSS踩下小狗梳洗的持续时间和总的孕产妇保健，哺乳期的第9天（侄子和桥梁2011年， 图2）在30分钟的视频录制。在哺乳期，侵略和自我疏导的第16天，衡量焦虑，增加（侄子和桥梁2011年， 图3）。牛奶摄入由CSS大坝幼崽少40％，比9和16天的哺乳（ 图4）控制水坝，小狗增长衰减这些天（侄子和桥梁2011年， 图5）。糖精偏好较低的第16天，在CSS处理水坝（ 图6）。 在成年雌性后代F1 CSS处理水坝，牛奶摄入量（ 图7）和糖精偏好（ 图8）2和16天郁闷。视上核催产素基因表达的降低这些水坝（ 图9 </strONG&gt;）和中央杏仁核，下丘脑室旁核，内侧杏仁核（穆加特罗伊德和侄子，2012）报告了类似的结果。 <table border="1"><tbody><tr><td> 行为 </td><td> 说明 </td></tr><tr><td>恢复</td><td>回巢账面幼崽</td></tr><tr><td>全检索</td><td>需要时间来检索所有8个幼崽</td></tr><tr><td>嵌套</td><td>嘴或爪子操纵的床上用品在巢区</td></tr><tr><td>小狗美容</td><td>小狗的皮毛和爪子舔或操纵</td></tr><tr><td>护理</td><td> ，当大坝是在蹲下或俯卧护理姿势</td></tr><tr><td>总孕产期保健服务</td><td>总硬脑膜重刑的嵌套，小狗美容及护理</td></tr><tr><td>自助美容</td><td>水坝操纵自己的毛皮与嘴或爪子</td></tr><tr><td>活动</td><td>任何不伴有上述行为的自发活动</td></tr></tbody></table> 表1中。孕产妇保健。 <table border="1"><tbody><tr><td> 行为 </td><td> 说明 </td></tr><tr><td>攻击</td><td>拳击或对付入侵者男</td></tr><tr><td>陈必亭</td><td>使用牙齿来攻击入侵者男</td></tr><tr><td>踢</td><td>使用脚罢工入侵者男性，类似兔子踢</td></tr><tr><td>钢钉</td><td>产妇的女性与男性四肢或身体</td></tr><tr><td>至TAL侵略</td><td>攻击的持续时间求和，咬，踢，钢钉</td></tr></tbody></table> 表2中。产妇侵略。 <img src="/files/ftp_upload/50324/50324fig1.jpg" alt="图1" /> 图1。慢性社会压力协议时间表。 <img src="/files/ftp_upload/50324/50324fig2.jpg" alt="图2" /> 图2。慢性社会压力降低孕产妇保健，哺乳期的第9天。公开哺乳坝的一种新型的男性入侵者7天，每天一小时减少所花费的时间的小狗美容及总孕产妇保健，包括小狗梳洗，护理和筑巢行为产妇在30分钟的行为视频录制（侄子和桥梁，2011）。 *表示显着差异控制和应力克之间roups，P &lt;0.05，n的= 9-10。 <img src="/files/ftp_upload/50324/50324fig3.jpg" alt="图3" /> 图3。慢性社会压力增加产妇哺乳期16天的侵略和焦虑。公开哺乳坝的一种新型的男性入侵者为14天，每天一小时的持续时间增加（A）和（B）的侵略和自我疏导的频率和运动功能下降活动超过30分钟的产妇侵略视频录制（侄子和桥梁，2011）。 *表示控制和压力团体之间的显着差异，P &lt;0.05，N = 9-10。 <img src="/files/ftp_upload/50324/50324fig4.jpg" alt="图4" /> 图4。慢性社会压力，减少牛奶的摄入量的后代。总牛奶摄入量减少超过两小时护理间隔8-10幼仔窝在强调水坝9和第16天的哺乳期。 *表示一个控制和应激组，P &lt;0.05，N = 12-14之间的显着差异。 <img src="/files/ftp_upload/50324/50324fig5.jpg" alt="图5" /> 图5。慢性社会压力衰减小狗增长9和第16天的哺乳期。15天的哺乳期间结果在减毒小狗的增长（侄子和桥梁2011）公开水坝慢性社会压力。 *表示控制和压力团体之间的显着差异，P &lt;0.05，N = 9-10。 <img src="/files/ftp_upload/50324/50324fig6.jpg" alt="图6" /> 图6。慢性社会压力导致糖精摄入量减少哺乳期16天。十五天的社会压力，降低了水超过17小时的时间内摄入的糖精相对百分比。 *表示显着DIF控制和压力团体之间的干扰，P &lt;0.05，N = 9-10。 <img src="/files/ftp_upload/50324/50324fig7.jpg" alt="图7" /> 图7。慢性早期生活的社会压力减少牛奶的摄入量由的后代F1大坝。F1水坝（产仔8-10幼仔），超过两小时护理区间的后代的牛奶摄入量减少2和16天的哺乳期。 *表示一个控制和应激组，P &lt;0.05，N = 12-14之间的显着差异。 <img src="/files/ftp_upload/50324/50324fig8.jpg" alt="图8" /> 图8。慢性早期生活的社会压力导致糖精摄入量下降，泌乳天2和16。十五天的社会压力，降低了水超过17小时的时间内摄入糖精相对百分比。 *表示控制和压力之间的显着差异组，P &lt;0.05，N = 12-14。 <img src="/files/ftp_upload/50324/50324fig9.jpg" alt="图9" /> 图9所示。慢性早期生活的社会压力减小视上核催产素mRNA的表达，成年雌性后代大坝暴露在慢性社会压力，，有减毒中央催产素的活性，这与护理下降的效率（穆加特罗伊德和侄子，2012年）。反对三个看家联合基因OXT的mRNA表达水平正常化，b-肌动蛋白，次黄嘌呤磷酸（HPRT）和甘油 - 3 - 磷酸脱氢酶（GAPDH）*表示一个显著差异控制和应力群体之间，p &lt;0.05，n的= 16-18。

Watch this Scientific Journal Video about Using Chronic Social Stress to Model Postpartum Depression in Lactating Rodents at JoVE.com

Using Chronic Social Stress to Model Postpartum Depression in Lactating Rodents

本文介绍了慢性居民入侵者使用社会压力一个ethologically相关的范式模型产后哺乳期啮齿动物的抑郁和焦虑。

哺乳期鼠害使用慢性社会压力型号产后抑郁症

Exposure to chronic stress is a reliable predictor of depressive disorders, and social stress is a common ethologically relevant stressor in both animals ...

using-chronic-social-stress-to-model-postpartum-depression-lactating

Research

JoVE Journal

Behavior

24.6K 次观看.  Tufts University Cummings School of Veterinary Medicine. 本文介绍了慢性居民入侵者使用社会压力一个ethologically相关的范式模型产后哺乳期啮齿动物的抑郁和焦虑。

视频: Using Chronic Social Stress to Model Postpartum Depression in Lactating Rodents

A Mouse Model of Subchronic and Mild Social Defeat Stress for Understanding Stress-induced Behavioral and Physiological Deficits

Stressful life events often increase the incidence of depression in humans. To study the mechanisms of depression, the development of animal models of depression is essential. Because there are several types of depression, various animal models are needed for a deeper understanding of the disorder. Previously, a mouse model of subchronic and mild social defeat stress (sCSDS) using a modified chronic social defeat stress (CSDS) paradigm was established. In the paradigm, to reduce physical injuries from aggressors, the duration of physical contact between the aggressor and a subordinate was reduced compared to in the original CSDS paradigm. sCSDS mice showed increased body weight gain, food intake, and water intake during the stress period, and their social behaviors were suppressed after the stress period. In terms of the face validity of the stress-induced overeating and overdrinking following the increased body weight gain, the sCSDS mice may show some features related to atypical depression in humans. Thus, a mouse model of sCSDS may be useful for studying the pathogenic mechanisms underlying depression. This protocol will help establish the sCSDS mouse model, especially for studying the mechanisms underlying stress-induced weight gain and polydipsia- and hyperphagia-like symptoms.

Here, methods for developing a mouse model of subchronic and mild social defeat stress are described and used to investigate the pathogenic features of depression including hyperphagia- and polydipsia-like symptoms following increased body weight.

亚慢性和温和的社会失败应激的小鼠模型理解应激诱导行为和生理赤字

Stressful life events often increase the incidence of depression in humans. To study the mechanisms of depression, the development of animal models of ...

科研

行为学

The Social Dimension of Stress: Experimental Manipulations of Social Support and Social Identity in the Trier Social Stress Test

In many situations humans are influenced by the behavior of other people and their relationships with them. For example, in stressful situations supportive behavior of other people as well as positive social relationships can act as powerful resources to cope with stress. In order to study the interplay between these variables, this protocol describes two effective experimental manipulations of social relationships and supportive behavior in the laboratory. In the present article, these two manipulations are implemented in the Trier Social Stress Test (TSST)&#8212;a standard stress induction paradigm in which participants are subjected to a simulated job interview. More precisely, we propose (a) a manipulation of the relationship between different protagonists in the TSST by making a shared social identity salient and (b) a manipulation of the behavior of the TSST-selection committee, which acts either supportively or unsupportively. These two experimental manipulations are designed in a modular fashion and can be applied independently of each other but can also be combined. Moreover, these two manipulations can also be integrated into other stress protocols and into other standardized social interactions such as trust games, negotiation tasks, or other group tasks.

Previous research on the social dimension of stress has focused on two important variables: social identity and social support. This protocol introduces an effective experimental manipulation of these two social variables and describes their implementation in a standard stress induction paradigm (Trier Social Stress Test).

应力的社会问题:社会支持和社会认同的特里尔社会的实验操作压力测试

In many situations humans are influenced by the behavior of other people and their relationships with them. For example, in stressful situations ...

An Unpredictable Chronic Mild Stress Protocol for Instigating Depressive Symptoms, Behavioral Changes and Negative Health Outcomes in Rodents

Chronic, unresolved stress is a major risk factor for the development of clinical depression. While many preclinical models of stress-induced depression have been reported, the unpredictable chronic mild stress (UCMS) protocol is an established translationally-relevant model for inducing behavioral symptoms commonly associated with clinical depression, such as anhedonia, altered grooming behavior, and learned helplessness in rodents. The UCMS protocol also induces physiological (e.g., hypercortisolemia, hypertension) and neurological (e.g., anhedonia, learned helplessness) changes that are clinically associated with depression. Importantly, UCMS-induced depressive symptoms can be ameliorated through chronic, but not acute, treatment with common SSRIs. As such, the UCMS protocol offers many advantages over acute stress protocols or protocols that utilize more extreme stressors. Our protocol involves randomized, daily exposures to 7 distinct stressors: damp bedding, removal of bedding, cage tilt, alteration of light/dark cycles, social stresses, shallow water bath, and predator sounds/smells. By subjecting rodents 3-4 hr daily to these mild stressors for 8 weeks, we demonstrate both significant behavioral changes and poor health outcomes to the cardiovascular system. This approach allows for in-depth interrogation of the neurological, behavioral, and physiological alterations associated with chronic stress-induced depression, as well as for testing of new potential therapeutic agents or intervention strategies.

The unpredictable chronic mild stress (UCMS) protocol is a validated method for studying behavioral and physiological changes associated with chronic stress and depressive symptoms. Eight weeks of imposition of the UCMS protocol induces behavioral changes and poor health outcomes in rodents of either gender.

煽动抑郁症状，行为变化和不利健康结果鼠害一个不可预知的慢性轻度应激协议

Chronic, unresolved stress is a major risk factor for the development of clinical depression. While many preclinical models of stress-induced depression ...

The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice

Depression is a highly prevalent and debilitating condition, only partially addressed by current pharmacotherapies. The lack of response to treatment by many patients prompts the need to develop new therapeutic alternatives and to better understand the etiology of the disorder. Pre-clinical models with translational merits are rudimentary for this task. Here we present a protocol for the unpredictable chronic mild stress (UCMS) method in mice. In this protocol, adolescent mice are chronically exposed to interchanging unpredictable mild stressors. Resembling the pathogenesis of depression in humans, stress exposure during the sensitive period of mice adolescence instigates a depressive-like phenotype evident in adulthood. UCMS can be used for screenings of antidepressants on the variety of depressive-like behaviors and neuromolecular indices. Among the more prominent tests to assess depressive-like behavior in rodents is the sucrose preference test (SPT), which reflects anhedonia (core symptom of depression). The SPT will also be presented in this protocol. The ability of UCMS to induce anhedonia, instigate long-term behavioral deficits and enable reversal of these deficits via chronic (but not acute) treatment with antidepressants strengthens the protocol&#39;s validity compared to other animal protocols for inducing depressive-like behaviors.

Here we present the unpredictable chronic mild stress protocol in mice. This protocol induces a long-term depressive-like phenotype and enables to assess the efficacy of putative antidepressants in reversing the behavioral and neuromolecular depressive-like deficits.

诱导小鼠快感缺失的不可预测慢性轻度应力协议

Depression is a highly prevalent and debilitating condition, only partially addressed by current pharmacotherapies. The lack of response to treatment by ...

Enactive Phenomenological Approach to the Trier Social Stress Test: A Mixed Methods Point of View

The single Trier Social Stress Test (TSST) and the TSST for groups (TSST-G) are the most used protocols to experimentally induce psychosocial stress. These tests are based on uncontrollability and social-evaluative threat, inducing psychological and physiological consequences (e.g., anxiety, emotional states, salivary cortisol increases). Many quantitative experimental studies have investigated these stress inducers and these consequences. But, as far as we know, this study is the first to provide a qualitative analysis to access the participants' voices so as to understand the dynamics of their experience throughout the TSST and the TSST-G. This paper outlines a mixed methods approach to the TSST. This approach can help to maximize the information that can be gained from the TSST, which researchers often use without looking more closely at what is qualitatively happening psychologically for participants during the stressor itself. In this way, this protocol is an example of mixed methods, showing the added value of using the enactive phenomenological approach to analyze experimental protocols more deeply. This kind of mixed methods is helpful to access the experience, to understand the actor's point of view, and to analyze in-depth the dynamics of cognitive processes like intentions, perceptions, enacted knowledge, and emotion. The discussion section shows the different uses of a mixed methods protocol, exploiting the enactive phenomenological approach to analyze a protocol or to give a cross vision of the same research subject. This section deals with different existing applications, pointing out some critical steps in this mixed methods approach.

Here, we present an original mixed method combining a quantitative and a qualitative approach to examine accurately participants&#39; experiences during the Trier Social Stress Test and the Trier Social Stress Test for groups.

研究者社会压力测试的现象学研究: 一种混合方法的观点

The single Trier Social Stress Test (TSST) and the TSST for groups (TSST-G) are the most used protocols to experimentally induce psychosocial stress. ...

Using Facial Electromyography to Assess Facial Muscle Reactions to Experienced and Observed Affective Touch in Humans

"Affective" touch is believed to be processed in a manner distinct from discriminatory touch and to involve activation of C-tactile (CT) afferent fibers. Touch that optimally activates CT fibers is consistently rated as hedonically pleasant. Patient groups with impaired social-emotional functioning also show disordered affective touch ratings. However, relying on self-reported ratings of touch has many limitations, including recall bias and communication barriers. Here, we describe a methodological approach to study affective responses to touch via facial electromyography (EMG) that circumvents the reliance on self-report ratings. Facial EMG is an objective, quantitative, and non-invasive method to measure facial muscle activity indicative of affective responses. Responses can be assessed across healthy and patient populations without the need for verbal communication. Here, we provide two separate datasets demonstrating that CT-optimal and non-optimal touch elicit distinct facial muscle reactions. Moreover, facial EMG responses are consistent across stimulus modalities, e.g. tactile (experienced touch) and visual (observed touch). Finally, the temporal resolution of facial EMG can detect responses on timescales that supersede that of verbal reporting. Together, our data suggest that facial EMG is a suitable methodology for use in affective tactile research that can be used to supplement, or in some cases, supplant, existing measures.

We describe a protocol to assess facial muscle activity in response to experienced and observed tactile stimulation using facial electromyography.

面部肌电图对人体有经验和观察到的情感触觉的影响评估

"Affective" touch is believed to be processed in a manner distinct from discriminatory touch and to involve activation of C-tactile (CT) afferent fibers. ...

A Chronic Immobilization Stress Protocol for Inducing Depression-Like Behavior in Mice

Depression is not yet fully understood, but various causative factors have been reported. Recently, the prevalence of depression has increased. However, therapeutic treatments for depression or research on depression is scarce. Thus, in the present paper, we propose a mouse model of depression induced by movement restriction. Chronic mild stress (CMS) is a well-known technique to induce depressive-like behavior. However, it necessitates a complex procedure consisting of a combination of various mild stresses. In contrast, chronic immobilization stress (CIS) is a readily accessible chronic stress model, modified from a restraint model that induces depressive behavior by restricting movement using a restrainer for a certain period. To evaluate the depressive-like behaviors, the sucrose preference test (SPT), the tail suspension test (TST), and the ELISA assay to measure stress marker corticosterone levels are combined in the present experiment. The described protocols illustrate the induction of CIS and evaluation of the changes in behavior and physiological factors for the validation of depression.

This article provides a simplified and standardized protocol for induction of depressive-like behavior in chronically immobilized mice by using a restrainer. In addition, behavior and physiological techniques to verify induction of depression are explained.

诱导小鼠抑郁行为的慢性固定性压力协议

Depression is not yet fully understood, but various causative factors have been reported. Recently, the prevalence of depression has increased. However, ...

A System for Tracking the Dynamics of Social Preference Behavior in Small Rodents

Exploring the neurobiological mechanisms of social behavior requires behavioral tests that can be applied to animal models in an unbiased and observer-independent manner. Since the beginning of the millennium, the three-chamber test has been widely used as a standard paradigm to evaluate sociability (social preference) and social novelty preference in small rodents. However, this test suffers from multiple limitations, including its dependence on spatial navigation and negligence of behavioral dynamics. Presented and validated here is a novel experimental system that offers an alternative to the three-chamber test, while also solving some of its caveats. The system requires a simple and affordable experimental apparatus and publicly available open-source analysis system, which automatically measures and analyzes multiple behavioral parameters at individual and population levels. It allows detailed analysis of the behavioral dynamics of small rodents during any social discrimination test. We demonstrate the efficiency of the system in analyzing the dynamics of social behavior during the social preference and social novelty preference tests as performed by adult male mice and rats. Moreover, we validate the ability of the system to reveal modified dynamics of social behavior in rodents following manipulations such as whisker trimming. Thus, the system allows for rigorous investigation of social behavior and dynamics in small rodent models and supports more accurate comparisons between strains, conditions, and treatments.

Described here is a novel automated experimental system that offers an alternative to the three-chamber test and also solves several caveats. This system supplies multiple behavioral parameters that enable rigorous analysis of small rodent behavioral dynamics during the social preference and social novelty preference tests.

跟踪小啮齿动物社会偏好行为动态的系统

Exploring the neurobiological mechanisms of social behavior requires behavioral tests that can be applied to animal models in an unbiased and ...

Chronic Stress Shifts Effort-Related Choice Behavior in a Y-Maze Barrier Task in Mice

Mood disorders, including major depressive disorder, can be precipitated by chronic stress. The Y-maze barrier task is an effort-related choice test that measures motivation to expend effort and obtain reward. In mice, chronic stress exposure significantly impacts motivation to work for a higher value reward when a lesser value reward is freely available compared to unstressed mice. Here we describe the chronic corticosterone administration paradigm, which produces a shift in effortful responding in the Y-maze barrier task. In the Y-maze task, one arm contains 4 food pellets, while the other arm contains only 2 pellets. After mice learn to select the high reward arm, barriers with progressively increasing height are then introduced into the high reward arm over multiple test sessions. Unfortunately, most chronic stress paradigms (including corticosterone and social defeat) were developed in male mice and are less effective in female mice. Therefore, we also discuss chronic non-discriminatory social defeat stress (CNSDS), a stress paradigm we developed that is effective in both male and female mice. Repeating results with multiple distinct chronic stressors in male and female mice combined with increased usage of translationally relevant behavior tasks will help to advance the understanding of how chronic stress can precipitate mood disorders.

The Y-maze barrier task is a behavior test that examines motivation to expend effort for reward. Here, we discuss testing multiple well-validated chronic stressors including chronic corticosterone and social defeat stress with this behavior, as well as the novel chronic non-discriminatory social defeat stress (CNSDS), which is effective in females.

在小鼠的 Y-Maze 障碍任务中，慢性应力转移与工作量相关的选择行为

Mood disorders, including major depressive disorder, can be precipitated by chronic stress. The Y-maze barrier task is an effort-related choice test that ...

Animal Models of Depression - Chronic Despair Model (CDM)

Major depressive disorder is one of the most prevalent forms of mental illnesses and causes tremendous individual suffering and socioeconomic burden. Despite its importance, current pharmacological treatment is limited, and novel treatment options are urgently needed. One key factor in the search for potential new drugs is evaluating their anti-depressive potency in appropriate animal models. The classical Porsolt forced swim test was used for this purpose for decades to induce and assess a depressive-like state. It consists of two short periods of forced swimming: the first to induce a depressed state and the second on the following day to evaluate the antidepressant effect of the agent given in between the two swim sessions. This model might be suitable as a screening tool for potential antidepressive agents but ignores the delayed onset of action of many antidepressants. The CDM was recently established and represented a modification of the classical test with notable differences. Mice are forced to swim for 5 consecutive days, following the idea that in humans, depression is induced by chronic rather than by acute stress. In a resting period of several days (1-3 weeks), animals develop sustained behavioral despair. The standard read-out method is the measurement of immobility time in an additional delayed swim session, but several alternative methods are proposed to get a broader view of the mood status of the animal. Multiple analysis tools can be used targeting behavioral, molecular, and electrophysiological changes. The depressed phenotype is stable for at least 4 weeks, providing a time window for rapid but also subchronic antidepressant treatment strategies. Furthermore, alterations in the development of a depressive-like state can be addressed using this approach. CDM, therefore, represents a useful tool to better understand depression and to develop novel treatment interventions.

Animal Models of Depression - Chronic Despair Model CDM

The chronic despair mouse model (CDM) of depression consists of repetitive forced swim sessions and another delayed swim phase as a read-out. It represents a suitable model for induction of a chronic depressive-like state stable for at least 4 weeks, amendable to evaluate subchronic and acute treatment interventions.

抑郁症的动物模型 - 慢性绝望模型（CDM）

Major depressive disorder is one of the most prevalent forms of mental illnesses and causes tremendous individual suffering and socioeconomic burden. ...