作者感谢博士。长冈健太郎（东京农工大学）和饭尾涉（茨城县）的有益的讨论。这项研究是由农业和医学科学（IUCAM）（文部科学省，日本）和研究项目上的农产品和健康促进的好处食品的发展（NARO）之间的茨城大学合作的部分资助（农林水产省，日本） 。

动物研究，批准并满足两个动物护理和茨城大学使用委员会和教育，文化，体育，科学部，技术部（MEXT），日本（71号通知）的准则。该协议的一个完整的概述如图 1所示。 1.仪器<ol><li>配制2种笼:单笼（宽（W）×深度研究[D]×高[H] =143毫米×293毫米×148毫米），和"社会溃败（SD）"笼（W×D× H = 220毫米×320毫米×135毫米）。 </li><li> 如图2，划分的SD笼成两个室与丙烯酸类透明板分频器（5mm厚）15圆形孔（3×5的矩阵:直径8mm）。 </li><li>获得云杉树，纯净，减肥食品颗粒和饮用水瓶用木头做刮片。此外，获得纸巾，掩模，和乳胶手套。 </li&gt; <li>对于社会互动测试，准备旷场竞技场（W×D×H =40厘米×40厘米×40厘米）采用灰聚氯乙烯，由钢（190克）的重量，和一个塑料互动盒（W ×D×H =10厘米×10厘米×13厘米; 100克）与三线目窗（W×D =5厘米×5厘米）（ 图3）。 </li><li>将CCD摄像机（2.8-12毫米; F = 1:1.4; 1/3英寸CCD）和自动跟踪系统，在行为测试室在动物设施。放置一个适当的搁板为鼠标笼在行为测试室使其习惯小鼠到测试室的环境中至少30分钟。 </li></ol> 2.习惯化的环境<ol><li>使用雄性C57BL / 6JJmsSlc（B6）小鼠的7周龄，雄SLC:ICR（ICR）小鼠超过5个月大，并提供从动物养殖公司的设施。 </li><li>独立移动两组B6小鼠（N=每组12只），以该设施;使用一组（筛选B6小鼠）筛选积极的ICR小鼠，另一组（受B6小鼠）为发展sCSDS模型。 </li><li>为了筛选自己的侵略行为引入ICR 小鼠 （n = 12）的设施。 </li><li>众议院小鼠分别单笼1周下一个12小时的明暗周期（约100勒克斯日光灯，灯上08:00）恒温（约23℃）和湿度（40％左右）为了他们，观察者到环境中。通过将使得小鼠不受相邻的小鼠的行为的笼之间白色的塑料板划分每个笼子。 </li><li>使纯化饮食的食物颗粒和反渗透水可用自由采食。使用AIN-93G食物由于其他非纯化饲粮颗粒的成分可以变化。 </li><li>测量体重，食物摄入（FI），和水的摄入的小鼠的（WI）的每一天。计算的B从最初的天ODY体重增加（BWG）。 </li></ol> 3.筛选积极ICR小鼠<ol><li> （:00-17:00 14），下午;习惯为如上所述，1周后，使用驻留-入侵者测试为3分钟试验用筛B6小鼠（8周龄入侵者）筛选ICR鼠（居民）下的大约300勒克司，在容纳室的照明。 <ol><li>具体而言，测试每个ICR小鼠每天三次试验，连续5天（共15次试验）对许多不同的B6小鼠可以找到它ICR小鼠表现出较高的侵略朝入侵者。在测试过程中，记录发作潜伏期和持续时间的攻击行为（快速动作与攻击咬）。 </li></ol></li><li>通过检查损伤伤口B6入侵者只，分别经审讯查明超积极的ICR小鼠。 </li><li>计算试验的比率，其中所述攻击延迟小于30秒作为侵略得分的第一索引。 </li><li> Calculate试验的比率，其中所述攻击延迟小于3分钟作为侵略得分的第二折射率。 </li><li>评估从第一个索引侵略分数。使用第二索引当第一索引相等。 </li><li>选择ICR小鼠具有较高的攻击得分不超攻击行为是积极的ICR小鼠。反复使用积极的ICR小鼠在整个下一组实验，直到大约12个月的年龄;然而，如上所述每个实验之前确认ICR小鼠的攻击性侵略性ICR小鼠进行筛选过程。 </li><li>筛选每次会议之后，记录筛选B6小鼠的损伤程度。如果鼠标受伤，隔离鼠标在单个笼并通过检查它的体重增加，食物摄入量和水摄入量观察进展。在影响生理和行为在小鼠中因伤重的情况下，根据当地的安乐死我他们ACUC准则。 </li></ol> 4. sCSDS <ol><li> （-6天）的初始应力曝光（第1天）和房子的天单独在单一笼小鼠将它们，观察者到环境中前7天引进主体B6小鼠。 </li><li> 1天（上 - 2日）前三天，将积极的ICR小鼠到每个SD笼子里，它是由丙烯酸分频器，让小鼠建立自己的领地，在SD笼（视B6相同数量的隔间老鼠）。 </li><li>通过使用白色的分割板，如在上述的单笼条件划分的SD笼中。 </li><li>对于非强调控制B6小鼠，制备的SD笼（小鼠数量的一半），以保持所述小鼠对;放置两只小鼠到每个隔室10天的SD笼由分频器分频。 </li><li>第1天每天BWG，FI和无线测量后，地方主体B6小鼠到SD笼中AFTE车厢（居民家笼）之一rnoon（14:00-16:00）下的约300勒克斯的房屋室内照明和测量从第一次进攻咬的身体接触的时间来完成驻地 - 入侵者试验。 </li><li>第1天，从第一次发作咬设置物理接触时间为5分钟，并且已经观察计数攻击叮咬ICR小鼠如由Miczek 等人所优先针对对手的背面或侧面的数 。20，以确定物理应力与B6小鼠的程度。 </li><li>物理接触时间后，救援受B6小鼠，检查并记录它们的皮毛状态和创伤。然后，将B6小鼠到另一个隔室旁边的ICR小鼠在SD笼子，直到暴露于物理应力的第二天。 </li><li>因为在SD笼丙烯酸分频器是透明的并且包含孔，露出主体B6小鼠对各种情绪压力，包括视觉，听觉，和嗅觉刺激，从ICR小鼠在邻近舱室换货的SD笼24小时每一天。 </li><li>每天测量BWG，FI和无线控制B6小鼠，然后将它们放置到每个隔间的SD笼1天。 </li><li>第2天，BWG，FI和无线的日常测试后，推出主题B6小鼠成其他ICR小鼠的领土暴露他们生理上的压力。 </li><li>将身体接触的时间从第2天第一次进攻咬住4.5分钟，并计算攻击咬伤的人数。 </li><li>移动控制B6小鼠成不同的车厢和改变对组合，以每天洗牌对的位置和合作伙伴。 </li><li>减少的身体接触的持续时间由每天0.5分钟，以便在第10天的持续时间从第一攻击咬设定为0.5分钟。 </li><li>在第7天，更换约一半的刨花在所有在SD笼隔间。 </li><li>接触到的最后一个物理应力在第10天之后，将受B6小鼠成单笼。类似的主题B6小鼠，移动控制B6小鼠成单笼在第10天。 </li><li>如果ICR小鼠没有表现出任何攻击咬伤，直到5分钟，每个试验的第一天到10，终止审理。更换ICR小鼠有备用积极的ICR小鼠，并进行替换试验为主题B6鼠标。 </li><li>如果鼠标受伤，隔离鼠标在单个笼并通过检查它的体重增加，食物摄入量和水摄入量观察进展。按照镇痛的IACUC的指导方针。在影响生理和行为在小鼠严重伤口的情况下，根据当地IACUC准则安乐死它们。 </li></ol> 5.社会回避试验（社会互动测试） <ol><li>在第11天（00:00-12 09）的社交回避在上午进行行为测试。 </li><li>在测试前30分钟，将控制转移并受B6小鼠的笼上的架子（微光小于1勒克斯）的行为下小于20勒克斯照明检测室，以允许他们使其习惯到环境中。 </li><li>为了减少订单的影响，交替测试控制并受B6小鼠。 </li><li>清洁的开放字段竞技场（照射该场的中心的光的20勒克斯），用浸透70％乙醇的行为测试之前对每只小鼠以除去粪便，尿纸巾一个塑料相互作用盒，和任何气味。 </li><li>从该开场装置附近的单一笼放置一个不熟悉的ICR小鼠（不用作侵略者）。 </li><li>放置B6小鼠到空相互作用盒的开口字段，如图4。监测和使用自动分析系统（在步骤5.10中所述）分析其行为2.5分钟。 </li><li>一审判决后，从现场移除B6老鼠，并将其放置到其家笼。 </li><li>在此之后，将不熟悉的雄性ICR小鼠（社会目标）到互动框，然后介绍了B6鼠标放在田野里并监督其2.5分钟的行为。 </li><li>二审后，返回无论是B6和ICR小鼠其家笼，并清理现场和互动框，上面提到的。 </li><li>重复这些步骤，为每个B6鼠标，以检验其社会行为。在每次试验中，使用记录顶视图电影CCD照相机。 <ol><li>行为测试后，计算每个试验花费在相互作用区（以秒为单位），并在角落区（以秒为单位），如图Goto等13的时间。判断鼠标的基于鼠标的中心的位置。 </li><li>计算社会互动分数作为100×（相互作用时间，用靶）/（相互作用时间，无靶标），以下发表在克里希南等人 21的方法。 </li></ol></li></ol>

<ol>
	<li>Heim, C., Binder, E. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Current+research+trends+in+early+life+stress+and+depression:+Review+of+human+studies+on+sensitive+periods,+gene-environment+interactions,+and+epigenetics.">Current research trends in early life stress and depression: Review of human studies on sensitive periods, gene-environment interactions, and epigenetics.</a> Exp. Neurol. 233 (1), 102-111 (2012).</li><li>Whiteford, H. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Global+burden+of+disease+attributable+to+mental+and+substance+use+disorders:+findings+from+the+Global+Burden+of+Disease+Study+2010.">Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010.</a> Lancet. 382 (9904), 1575-1586 (2013).</li><li>Ferrari, A. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+Burden+Attributable+to+Mental+and+Substance+Use+Disorders+as+Risk+Factors+for+Suicide:+Findings+from+the+Global+Burden+of+Disease+Study+2010.">The Burden Attributable to Mental and Substance Use Disorders as Risk Factors for Suicide: Findings from the Global Burden of Disease Study 2010.</a> PLoS ONE. 9 (4), e91936 (2014).</li><li>Flint, J., Kendler, K. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+genetics+of+major+depression.">The genetics of major depression.</a> Neuron. 81 (3), 484-503 (2014).</li><li>Nestler, E. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neurobiology+of+Depression.">Neurobiology of Depression.</a> Neuron. 34 (1), 13-25 (2002).</li><li>Gold, P. W., Chrousos, G. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Organization+of+the+stress+system+and+its+dysregulation+in+melancholic+and+atypical+depression:+high+vs+low+CRH/NE+states.">Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states.</a> Mol. Psychiatry. 7 (3), 254-275 (2002).</li><li>O'Keane, V., Frodl, T., Dinan, T. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+review+of+atypical+depression+in+relation+to+the+course+of+depression+and+changes+in+HPA+axis+organization.">A review of atypical depression in relation to the course of depression and changes in HPA axis organization.</a> Psychoneuroendocrinology. 37 (10), 1589-1599 (2012).</li><li>Nestler, E. J., Hyman, S. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+of+neuropsychiatric+disorders.">Animal models of neuropsychiatric disorders.</a> Nat. Neurosci. 13 (10), 1161-1169 (2010).</li><li>Katz, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+and+human+depressive+disorders.">Animal models and human depressive disorders.</a> Neurosci. Biobehav. Rev. 5 (2), 231-246 (1981).</li><li>Krishnan, V., Nestler, E. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Animal+models+of+depression:+molecular+perspectives.">Animal models of depression: molecular perspectives.</a> Curr. Top. Behav. Neurosci. 7, 121-147 (2011).</li><li>Kudryavtseva, N. N., Bakshtanovskaya, I. V., Koryakina, L. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Social+model+of+depression+in+mice+of+C57BL/6J+strain.">Social model of depression in mice of C57BL/6J strain.</a> Pharmacol. Biochem. Behav. 38 (2), 315-320 (1991).</li><li>Miczek, K. A., Yap, J. J., Covington, H. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Social+stress,+therapeutics+and+drug+abuse:+preclinical+models+of+escalated+and+depressed+intake.">Social stress, therapeutics and drug abuse: preclinical models of escalated and depressed intake.</a> Pharmacol. Ther. 120 (2), 102-128 (2008).</li><li>Goto, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Subchronic+and+mild+social+defeat+stress+accelerates+food+intake+and+body+weight+gain+with+polydipsia-like+features+in+mice.">Subchronic and mild social defeat stress accelerates food intake and body weight gain with polydipsia-like features in mice.</a> Behav. Brain Res. 270, 339-348 (2014).</li><li>Goto, T., Kubota, Y., Toyoda, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Plasma+and+Liver+Metabolic+Profiles+in+Mice+Subjected+to+Subchronic+and+Mild+Social+Defeat+Stress.">Plasma and Liver Metabolic Profiles in Mice Subjected to Subchronic and Mild Social Defeat Stress.</a> J. Proteome Res. , (2014).</li><li>Iio, W., Matsukawa, N., Tsukahara, T., Kohari, D., Toyoda, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+chronic+social+defeat+stress+on+MAP+kinase+cascade.">Effects of chronic social defeat stress on MAP kinase cascade.</a> Neurosci. Lett. 504 (3), 281-284 (2011).</li><li>Iio, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+chronic+social+defeat+stress+on+peripheral+leptin+and+its+hypothalamic+actions.">Effects of chronic social defeat stress on peripheral leptin and its hypothalamic actions.</a> BMC Neurosci. 15 (72), (2014).</li><li>Iio, W., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Anorexic+behavior+and+elevation+of+hypothalamic+malonyl-CoA+in+socially+defeated+rats.">Anorexic behavior and elevation of hypothalamic malonyl-CoA in socially defeated rats.</a> Biochem. Biophys. Res. Commun. 421 (2), 301-304 (2012).</li><li>Crawley, J. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> What's Wrong With My Mouse?: Behavioral Phenotyping of Transgenic and Knockout Mice. , 978-970 (2007).</li><li>Golden, S. A., Covington, H. E., Berton, O., Russo, S. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+standardized+protocol+for+repeated+social+defeat+stress+in+mice.">A standardized protocol for repeated social defeat stress in mice.</a> Nat. Protoc. 6 (8), 1183-1191 (2011).</li><li>Miczek, K. A., Maxson, S. C., Fish, E. W., Faccidomo, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Aggressive+behavioral+phenotypes+in+mice.">Aggressive behavioral phenotypes in mice.</a> Behav. Brain Res. 125, 167-181 (2001).</li><li>Krishnan, V., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Molecular+adaptations+underlying+susceptibility+and+resistance+to+social+defeat+in+brain+reward+regions.">Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions.</a> Cell. 131 (2), 391-404 (2007).</li><li>Chuang, J. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+beta3-adrenergic-leptin-melanocortin+circuit+regulates+behavioral+and+metabolic+changes+induced+by+chronic+stress.">A beta3-adrenergic-leptin-melanocortin circuit regulates behavioral and metabolic changes induced by chronic stress.</a> Biol. Psychiatry. 67 (11), 1075-1082 (2010).</li><li>Warren, B. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neurobiological+sequelae+of+witnessing+stressful+events+in+adult+mice.">Neurobiological sequelae of witnessing stressful events in adult mice.</a> Biol. Psychiatry. 73 (1), 7-14 (2013).</li><li>Savignac, H. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Increased+sensitivity+to+the+effects+of+chronic+social+defeat+stress+in+an+innately+anxious+mouse+strain.">Increased sensitivity to the effects of chronic social defeat stress in an innately anxious mouse strain.</a> Neuroscience. 192, 524-536 (2011).</li><li>Green, J. G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Childhood+Adversities+and+Adult+Psychiatric+Disorders+in+the+National+Comorbidity+Survey+Replication+I:+associations+with+first+onset+of+DSM-IV+disorders.">Childhood Adversities and Adult Psychiatric Disorders in the National Comorbidity Survey Replication I: associations with first onset of DSM-IV disorders.</a> Arch. Gen. Psychiatry. 67 (2), 113-123 (2010).</li><li>Miniati, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+characteristics+and+treatment+outcome+of+depression+in+patients+with+and+without+a+history+of+emotional+and+physical+abuse.">Clinical characteristics and treatment outcome of depression in patients with and without a history of emotional and physical abuse.</a> J. Psychiatr. Res. 44 (5), 302-309 (2010).</li><li>Tao, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Examining+the+relationship+between+lifetime+stressful+life+events+and+the+onset+of+major+depression+in+Chinese+women.">Examining the relationship between lifetime stressful life events and the onset of major depression in Chinese women.</a> J. Affect. Disord. 135 (1-3), 95-99 (2011).</li><li>Valente, S., Fisher, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recognizing+and+managing+psychogenic+polydipsia+in+mental+health.">Recognizing and managing psychogenic polydipsia in mental health.</a> J. Nurse Pract. 6 (7), 546-550 (2010).</li><li>Dundas, B., Harris, M., Narasimham, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Psychogenic+Polydipsia+Review:+Etiology,+Differential,+and+Treatment.">Psychogenic Polydipsia Review: Etiology, Differential, and Treatment.</a> Curr. Psychiatry Rep. 9 (3), 236-241 (2007).</li><li>Tsumura, K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Downregulation+of+AQP2+expression+in+the+kidney+of+polydipsic+STR/N+mice.">Downregulation of AQP2 expression in the kidney of polydipsic STR/N mice.</a> Am. J. Physiol. Renal Physiol. 290 (2), F478-F485 (2006).</li><li>Flores, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Schedule-Induced+Polydipsia:+Searching+for+the+Endophenotype+of+Compulsive+Behavior.">Schedule-Induced Polydipsia: Searching for the Endophenotype of Compulsive Behavior.</a> World J. Neurosci. 4, 253-260 (2014).</li><li>Cryan, J. F., Dinan, T. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mind-altering+microorganisms:+the+impact+of+the+gut+microbiota+on+brain+and+and+behaviour.">Mind-altering microorganisms: the impact of the gut microbiota on brain and and behaviour.</a> Nat. Rev. Neurosci. 13 (10), 701-712 (2012).</li></ol>

作者宣称，他们有没有竞争的财务权益。

有sCSDS小鼠和CSDS小鼠进行标准CSDS协议19（与每天侵略者物理接触5至10分钟）之间的差异确定的体重。时的应力期间sCSDS小鼠显示增加BWG，而标准CSDS小鼠显示体重降低时的应力期间21,22,23。有这两种协议之间的侵略者与身体接触的总时长方面在10天的期限压力很大差异。而原来的CSDS范例包括侵略者和从属小鼠中总（全面CSDS）之间的物理相互作用的50或100分钟时，sCSDS方法包含这种相?...

多种压力事件发生在整个人类的生活。过大的应力常导致在人类和动物有害的生理后果。在人类中，压力事件是主要危险因素沉淀精神障碍，例如抑郁症1。疾病研究的全球负担表明，抑郁症是最致残性疾病的伤残调整寿命年（DALY）和多年居住残疾2项之一。此外，抑郁症占自杀的DALY 3的比例最大。患有抑郁症很难管理自己的生活，作为一个结果，他们的生活质量往往恶化。因此，强烈需要开发有效的治疗剂，以改善生活在这些患者中的质量。 许多研究的重大抑郁症被执行，并揭示了疾病susceptibilit的遗传贡献y为约30〜40％，这是由多个位点的小的影响4的作用进行说明。由于抑郁症背后的复杂的致病机理，疾病的病因的详细仍不清楚。临床报告显示，有抑郁症，亚型如忧郁和非典型抑郁症5，其显示降低的和分别6增加体重。虽然25-30％和抑郁症患者15-30％为纯忧郁和非典型特征，分别大多有两种亚型7的混合特征。因此，严重抑郁症有广泛的症状。为了找到生物标志物和开发目标的治疗剂的各类人类的抑郁症的，它建立凹陷8的几个不同的动物模型是重要的。 抑郁症的动物模型用几种方法已经建立了一个包括学无奈，慢性应激和慢性社会的失败应力（CSDS）9-12。丰田和同事建立大鼠和小鼠13-17的CSDS模型，以阐明代谢和与抑郁症相关的行为。由于抑郁症的动物模型是由表面效度18评估，在其中模型建立的环境是很重要的。此外，金等 19报道的方法进行详细创建CSDS小鼠。已知的是，在CSDS小鼠的社会行为的缺陷可以通过慢性治疗中回收，而不是由急性治疗，与抗抑郁药，而且它们在脑源性​​神经营养的调节方面共享的症状类似于在抑郁症患者因素6。 Goto等13以前开发的亚慢性和轻度社会败应力（sCSDS）小鼠模型通过修改方法金等人 。19。该sCSDS小鼠显示以下收益体重和增加身体水分含量13 polydipsia-和亢进样症状。在这份报告中，提供了协议建立sCSDS小鼠模型和我们讨论这个模型的效用。

<table border="0" cellpadding="0" cellspacing="0">
	<tbody>
		<tr>
			<td>single cage</td>
			<td>Charles River Laboratories Japan</td>
			<td></td>
			<td>width [W] &#215; depth [D] &#215; height [H] = 143 &#215; 293 &#215; 148 mm</td>
		</tr>
		<tr>
			<td>M cage</td>
			<td>Natsume Seisakusho</td>
			<td></td>
			<td>W &#215; D &#215; H = 220 &#215; 320 &#215; 135 mm</td>
		</tr>
		<tr>
			<td>Whiteflake</td>
			<td>Charles River Laboratories Japan</td>
			<td></td>
			<td>Wood-shaving chips made from spruce trees</td>
		</tr>
		<tr>
			<td>AIN-93G</td>
			<td>Oriental Yeast</td>
			<td></td>
			<td>purified-diet food pellets</td>
		</tr>
		<tr>
			<td>Kimtowel</td>
			<td>Nippon Paper Crecia Co.</td>
			<td></td>
			<td>Paper towels</td>
		</tr>
		<tr>
			<td>open-field arena</td>
			<td>O&#8217;Hara &#38; Co.</td>
			<td></td>
			<td>made of gray polyvinylchloride</td>
		</tr>
	</tbody>
</table>

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.

以监测物理应力的程度超过10天的期间，攻击叮咬ICR小鼠的数目由研究人员进行手动计数。 图5A指示各值接收攻击叮咬的数目。有在早期阶段（第1天约10-120叮咬）相当大的变化，但这种变化被减少了后期（第10天约为:5-20叮咬）。 图5B表示接收攻击叮咬的平均数量逐渐降低随着时间的推移，由于物理接触的持续时间减少（从5分钟至0.5分钟）。 受试者?...

Watch this Scientific Journal Video about A Mouse Model of Subchronic and Mild Social Defeat Stress for Understanding Stress-induced Behavioral and Physiological Deficits at JoVE.com

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

这里，为了开发亚慢性和轻度社会败应力的小鼠模型中的方法描述和用于研究抑郁症的致病特性，包括hyperphagia-和烦渴样症状以下增加体重。

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 ...

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Research

JoVE Journal

Behavior

19.6K 次观看.  Ibaraki University. 这里，为了开发亚慢性和轻度社会败应力的小鼠模型中的方法描述和用于研究抑郁症的致病特性，包括hyperphagia-和烦渴样症状以下增加体重。 

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

The Resident-intruder Paradigm: A Standardized Test for Aggression, Violence and Social Stress

This video publication explains in detail the experimental protocol of the resident-intruder paradigm in rats. This test is a standardized method to measure offensive aggression and defensive behavior in a semi natural setting. The most important behavioral elements performed by the resident and the intruder are demonstrated in the video and illustrated using artistic drawings. The use of the resident intruder paradigm for acute and chronic social stress experiments is explained as well. Finally, some brief tests and criteria are presented to distinguish aggression from its more violent and pathological forms.

This video shows the resident-intruder paradigm in rats. This test is a standardized method to measure offensive aggression, defensive behavior and violence in a semi-natural setting. The use of the paradigm for social stress experiments is explained as well.

驻地入侵者范式:一种标准化考试的侵略，暴力和社会压力

This video publication explains in detail the experimental protocol of the resident-intruder paradigm in rats. This test is a standardized method to ...

科研

行为学

Using Chronic Social Stress to Model Postpartum Depression in Lactating Rodents

Exposure to chronic stress is a reliable predictor of depressive disorders, and social stress is a common ethologically relevant stressor in both animals and humans. However, many animal models of depression were developed in males and are not applicable or effective in studies of postpartum females. Recent studies have reported significant effects of chronic social stress during lactation, an ethologically relevant and effective stressor, on maternal behavior, growth, and behavioral neuroendocrinology. This manuscript will describe this chronic social stress paradigm using repeated exposure of a lactating dam to a novel male intruder, and the assessment of the behavioral, physiological, and neuroendocrine effects of this model. Chronic social stress (CSS) is a valuable model for studying the effects of stress on the behavior and physiology of the dam as well as her offspring and future generations. The exposure of pups to CSS can also be used as an early life stress that has long term effects on behavior, physiology, and neuroendocrinology.

This article describes the use of chronic resident intruder social stress as an ethologically relevant paradigm to model postpartum depression and anxiety in lactating rodents.

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 ...

Moderate Prenatal Alcohol Exposure and Quantification of Social Behavior in Adult Rats

Alterations in social behavior are among the major negative consequences observed in children with Fetal Alcohol Spectrum Disorders (FASDs). Several independent laboratories have demonstrated robust alterations in the social behavior of rodents exposed to alcohol during brain development across a wide range of exposure durations, timing, doses, and ages at the time of behavioral quantification. Prior work from this laboratory has identified reliable alterations in specific forms of social interaction following moderate prenatal alcohol exposure (PAE) in the rat that persist well into adulthood, including increased wrestling and decreased investigation. These behavioral alterations have been useful in identifying neural circuits altered by moderate PAE1, and may hold importance for progressing toward a more complete understanding of the neural bases of PAE-related alterations in social behavior. This paper describes procedures for performing moderate PAE in which rat dams voluntarily consume ethanol or saccharin (control) throughout gestation, and measurement of social behaviors in adult offspring.

The goal of the protocol presented here is to describe procedures to expose rats to moderate levels of alcohol during prenatal brain development and to quantify resulting alterations in social behavior during adulthood.

适度的产前酒精暴露在成年大鼠社会行为的量化

Alterations in social behavior are among the major negative consequences observed in children with Fetal Alcohol Spectrum Disorders (FASDs). Several ...

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 ...

Detecting Behavioral Deficits in Rats After Traumatic Brain Injury

With the increasing incidence of traumatic brain injury (TBI) in both civilian and military populations, TBI is now considered a chronic disease; however, few studies have investigated the long-term effects of injury in rodent models of TBI. Shown here are behavioral measures that are well-established in TBI research for times early after injury, such as two weeks, until two months. Some of these methods have previously been used at later times after injury, up to one year, but by very few laboratories. The methods demonstrated here are a short neurological assessment to test reflexes, a Beam-Balance to test balance, a Beam-Walk to test balance and motor coordination, and a working memory version of the Morris water maze that can be sensitive to deficits in reference memory. Male rats were handled and pre-trained to neurological, balance, and motor coordination tests prior to receiving parasagittal fluid percussion injury (FPI) or sham injury. Rats can be tested on the short neurological assessment (neuroscore), the beam-balance, and the Beam-Walk multiple times, while testing on the water maze can only be done once. This difference is because rats can remember the task, thus confounding the results if repeated testing is attempted in the same animal. When testing from one to three days after injury, significant differences are detected in all three non-cognitive tasks. However, differences in the Beam-Walk task were not detectable at later time points (after 3 months). Deficits were detected at 3 months in the Beam-Balance and at 6 months in the neuroscore. Deficits in working memory were detected out to 12 months after injury, and a deficit in a reference memory first appeared at 12 months. Thus, standard behavioral tests can be useful measures of persistent behavioral deficits after FPI.

The goal of the behavioral tests presented here is to detect functional deficits in rats after traumatic brain injury. Four specific tests are presented that detect deficits in behaviors to reflect the damage to specific brain areas at times extending to one year after injury.

颅脑损伤后大鼠行为缺陷的检测

With the increasing incidence of traumatic brain injury (TBI) in both civilian and military populations, TBI is now considered a chronic disease; however, ...

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 ...

Stress-Enhanced Fear Learning, a Robust Rodent Model of Post-Traumatic Stress Disorder

Fear behaviors are important for survival, but disproportionately high levels of fear can increase the vulnerability for developing psychiatric disorders such as post-traumatic stress disorder (PTSD). To understand the biological mechanisms of fear dysregulation in PTSD, it is important to start with a valid animal model of the disorder. This protocol describes the methodology required to conduct stress-enhanced fear learning (SEFL) experiments, a preclinical model of PTSD, in both rats and mice. SEFL was developed to recapitulate critical aspects of PTSD, including long-term sensitization of fear learning caused by an acute stressor. SEFL uses aspects of Pavlovian fear conditioning but produces a distinct and robust sensitized fear response far greater than normal conditional fear responses. The trauma procedure involves placing a rodent in a conditioning chamber and administering 15 unsignaled shocks randomly distributed over 90 minutes (for rat experiments; for mouse experiments, 10 unsignaled shocks randomly distributed over 60 minutes are used). On day 2, rodents are placed in a novel conditioning context where they receive a single shock; then, on day 3 they are placed back in the same context as on day 2 and tested for changes in freezing levels. Rodents that previously received the trauma display enhanced levels of freezing on the test day compared to those that received no shocks on the first day. Thus, with this model, a single highly stressful experience (the trauma) produces extreme fear of the stimuli associated with the traumatic event.

Here we describe the detailed methodology required to conduct stress-enhanced fear learning (SEFL) experiments, a preclinical model of post-traumatic stress disorder, in both rats and mice. The model utilizes aspects of Pavlovian fear conditioning and freezing as an index of enhanced fear in rodents.

压力增强恐惧学习--创伤后应激障碍的健壮啮齿动物模型

Fear behaviors are important for survival, but disproportionately high levels of fear can increase the vulnerability for developing psychiatric disorders ...

A Visual Guide for Studying Behavioral Defenses to Pathogen Attacks in Leaf-Cutting Ants

The complex lifestyle, evolutionary history of advanced cooperation, and disease defenses of leaf-cutting ants are well studied. Although numerous studies have described the behaviors connected with disease defense, and the associated use of chemicals and antimicrobials, no common visual reference has been made. The main aim of this study was to record short clips of behaviors involved in disease defense, both prophylactically and directly targeted towards an antagonist of the colony following infection. To do so we used an infection experiment, with sub-colonies of the leaf-cutting ant species Acromyrmex echinatior, and the most significant known pathogenic threat to the ants&#39; fungal crop (Leucoagaricus gongylophorus), a specialized pathogenic fungus in the genus Escovopsis. We filmed and compared infected and uninfected colonies, at both early and more advanced stages of infection. We quantified key defensive behaviors across treatments and show that the behavioral response to pathogen attack likely varies between different castes of worker ants, and between early and late detection of a threat. Based on these recordings we have made a library of behavioral clips, accompanied by definitions of the main individual defensive behaviors. We anticipate that such a guide can provide a common frame of reference for other researchers working in this field, to recognize and study these behaviors, and also provide greater scope for comparing different studies to ultimately help better understand the role these behaviors play in disease defense.

We present a visual guide to disease defense behaviors in leaf-cutting ants, with individual clips and accompanying definitions, illustrated in an experimental infection scenario. Our main aim is to help other researchers recognize key defensive behaviors and to provide a common understanding for future research in this field.

叶切蚁病原体攻击行为防御研究的可视化指南

The complex lifestyle, evolutionary history of advanced cooperation, and disease defenses of leaf-cutting ants are well studied. Although numerous studies ...

Nest Building Behavior as an Early Indicator of Behavioral Deficits in Mice

Nest building is an innate behavior in male and female rodents, even when raised in laboratory settings. As such, many researchers provide rodents synthetic and/or natural materials (such as twine, tissue, cotton, paper, and hay) as a gauge of their overall well-being and as an ancillary assessment to predict the possible decline in cognition. Typically, changes in nesting behaviors, such as failure to create a nest, indicate a change in health or welfare. In addition, nesting behavior is sensitive to many environmental and physiological challenges, as well as many genetic mutations underlying pathological disease states. The following protocol describes a nesting behavior paradigm that explores the usage of four types of nesting material. In addition, the protocol utilizes intraclass correlations to demonstrate that inter-rater reliability is higher when nests are constructed out of shredded paper compared to other common nesting materials such as cotton squares, paper twists, and soft cob bedding. The chosen methodology and statistical considerations (i.e., intraclass correlation) for this assay may be of interest for those conducting experiments assessing the quality of living of mice.&#160;

Here, we present a protocol to quantify nest building behavior in mice, which is known to be impaired in several neurological disorders and diseases. This protocol examines the utility of four materials and offers the opportunity to quantify the rater agreement in scoring, improving the validity and reliability of the assay.