一种诱导大鼠抑郁症状行为的新方法
Summary
该协议描述了一种新的模型, 通过这种模式, 健康的大鼠可以在一定时间内收缩抑郁症, periodthrough 感染慢性不可预测的压力大鼠。
Abstract
传染性抑郁症是一个尚未得到充分承认的现象, 这源于对这个问题的材料不足。目前, 研究传染性抑郁症的行动、预防、遏制和治疗机制尚无现有的模式。因此, 本研究的目的是建立第一个传染性抑郁症动物模型。
健康的大鼠如果暴露在抑郁的大鼠身上, 就可以收缩抑郁行为。抑郁症是诱导大鼠, 使他们的几个操作的慢性不可预知的压力 (因为) 超过5周, 如协议所述。成功的蔗糖偏好试验证实了大鼠抑郁症的发展。被暴露的老鼠然后被囚禁与天真的老鼠从传染小组 (1 天真 rat/2 被压抑的老鼠在笼子) 另外5星期。30个社会群体是由被暴露的老鼠和天真的老鼠组合而成的。
这一提议的抑郁症传染协议的动物主要是由同居的暴露和健康的老鼠5周。为确保该方法行之有效, 首先进行了一系列的试验, 即在诱导抑郁症大鼠时的蔗糖偏好试验, 其次是在同居期结束时的野外和强迫游泳试验。在整个实验中, 老鼠被给予标记, 每次测试后都会返回笼子。
对此方法的一些限制是, 实验组和对照小组在蔗糖偏爱试验中的差异和强迫游泳试验不可逆转的创伤结果。在议定书今后的任何适用之前, 这些可能值得考虑是否适合。尽管如此, 在实验之后, 天真的老鼠在与被暴露的老鼠分享同一个笼子5周后, 形成了感染性抑郁症。
Introduction
最近进行的测试表明, 精神疾病可以很容易地传播到健康的人通过传染1。在这种情况下, 它被称为社会传染, 并通过影响, 态度或行为传播。这只需要一个抑郁的个体与一个或多个健康的个体互动, 从而促进情感的交流。社会关系是情绪的一个非常重要的组成部分, 因为它们定义了情感从一个个体转移到另一个人, 通过模仿和 “情感传染”。传染效果的时间框架会发生变化2, 不可避免地取决于情绪的严重性和接受者的抵抗力量。
情绪传染的重大后果确保了过去的研究主要集中在消极方面。负面影响的结果确保传染抑郁症得到了极大的关注, 研究表明, 传染抑郁症增加了家庭和朋友的抑郁症状的个人表现抑郁行为的可能性3,4,5,6。
解决抑郁症有个人和经济原因。它通常导致发病率;并且它的生存率在13.3 和17.1% 之间在美国7。世界卫生组织的档案显示, 抑郁症在全球疾病的名单上名列第四, 在所有性别、年龄、社会背景的人身上发生, 并同样能够造成健康不良, 影响到相互作用的能力。与其他8,9,10,11, 并导致多余的残疾12,13。估计每年有85万人丧生于抑郁症状的自杀事件14。患者通常是处方抗抑郁药物或建议接受认知行为治疗。这些 treatmentshelp 约60-80% 的病人。然而, 处理这一疾病仍然是一个大问题;治疗不适用于所有抑郁症患者。对于那些得到治疗的人, 有些会受到副作用, 而其他人则不遵守15指南。抗治疗的患者数量约为 40%14。随着抑郁症的出现, 经济经常以昂贵的治疗方式、劳动力的减少和提前退休16来承受。据估计, 美国每年损失440亿美元是由抑郁症造成的, 占该国丧失生产率的近一半为17。昂贵的治疗需要仔细的医疗照顾, 这招致了各种增加的医疗费用, 并要求预期的不良结局, 以及对治疗的不良反应18。
没有遇到一个已经被证实的动物模型来研究抑郁症-传染机制, 它的预防和治疗, 这一假想的动物协议首次使用。结果表明, 通过与暴露的大鼠同居, 健康的大鼠倾向于表达抑郁行为。这项实验的主要目的是建立一个实验室程序, 强调通过传染, 从暴露的老鼠到健康的抑郁症的转移。接下来, 评估结果, 以确定抑郁症传染是否仅限于抑郁症状, 或是否与其他情绪紊乱, 如焦虑有关。这项实验的最终目的是为了更好地了解抑郁症蔓延的机制, 以开发新的治疗方法19。
Protocol
根据《赫尔辛基和东京宣言》的建议以及欧洲共同体实验动物的使用准则, 执行了下列程序。实验也得到了古里安大学动物护理委员会的批准。 1. 为实验程序准备大鼠 注: 为实验程序, 选择雄性大大鼠无显性病理, 每重300至350克。 每笼三只老鼠, 有周和水可用的ad 随意,并允许至少两周的适应, 交替在12小时的日光和12小时的黑暗。 在实…
Representative Results
蔗糖首选项测试:在将大鼠暴露为诱导抑郁症的5周后, 然后再将健康的大鼠暴露给所暴露的大鼠, 再过5周, 两组大鼠在实验结束时表现出抑郁样的 behaviorsat (图 2)。这一行为的证据被认为是在减少了对蔗糖的偏好, 由抑郁症的老鼠, 在 (65 2.8%, p < 0.001,图 2) 相比, 30 大鼠在控制组 (101 @ 7%, (图 2)。10周后, 与对照组2只大鼠 (30 …
Discussion
根据本协议的应用结果, 在较长时间内, 健康大鼠与人类一样, 对抑郁大鼠有负面影响。打哈欠抑郁的大鼠在同居五周后受到抑郁的影响, 首次建立了明显的动物抑郁-传染模型。早先与猪的研究也建议了抑郁症和健康猪之间的共同情感法规25。
在大鼠抑郁症的诱导下, 通过应用。这种方法表达了每天的社会环境压力源的共同特征。档案显示, 以此为主要手段的?…
Disclosures
The authors have nothing to disclose.
Acknowledgements
作者感谢 Bilyar 博士, 住院医师, 泌尿系, Soroka 医疗中心, 他在实验室的帮助, 以及在视频分析。希拉 Ovadia 的支持, 动物资源股主任, 也感激地承认。许多人感谢卢旺达解放军和紧急护理股的工作人员, Soroka 医疗中心的支持和有益的讨论。
Materials
| Rat Cages | Techniplast | 2000P | Conventional housing for rodents. Was used for housing rats throughout the experiment |
| Water | – | – | Common tap water used througout the experiment at different stages |
| Purina Chow | Purina | 5001 | Rodent laboratory chow given to rats, mice and hamster is a life-cycle nutrition that has been used in biomedical researc for over 5 decades. Provided to rats ad libitum in this experiment |
| Bottles | Techniplast | ACBT0262SU | 150 ml bottles filled with 100 ml of water and 100 ml 1%(w/v) sucrose solution |
| Black lusterless perspex box | – | – | (120 cm × 60 cm × 60 cm), divided into a 25% central zone and the surrounding border zone |
| Video Camera | Canon | – | Digital video camera for high definition recording of rat behavior under open field test |
| Alcohol | Pharmacy | – | 99% pharmaceutical alcohol diluted to 5% and used for lceaning the open field test box before the introduction of each rat |
| Glass cylinder | – | – | 100 cm tall, 40 cm in diameter, and 40 cm deep cylinder used for carrying out the forced swim test |
| Paper towels | Pharmacy | – | Dry towels used for keeping rats dry after immersing them in water |
| Bold markers | – | – | Common bold markers used for labeling rats |
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Cite This Article
Zeldetz, V., Natanel, D., Boyko, M., Zlotnik, A., Shiyntum, H. N., Grinshpun, J., Frank, D., Kuts, R., Brotfain, E., Peiser, J. A New Method for Inducing a Depression-Like Behavior in Rats. J. Vis. Exp. (132), e57137, doi:10.3791/57137 (2018).