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。

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。
<ol><li>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。</li>
	<li>在实验开始之前, 用3天的蔗糖偏好测试 (参考步骤 4)测试所有老鼠是否存在抑郁症状行为。
</li>
	<li>排除被认为显示抑郁症状行为的老鼠, 以及那些与此类老鼠同住的笼子, 以避免抑郁症在实验开始前就可能扩散到未受影响的大鼠, 消除试验阳性的老鼠。抑郁;然后, 消灭与抑郁的老鼠在同一个笼子里的老鼠。</li>
	<li>如有必要, 随机排除额外的大鼠, 为抑郁症实验、30只大鼠感染组和 30 ratsforthe 对照组创建60只大鼠的最终组。</li>
	<li>标记老鼠 (使用编号的贴纸), 在整个实验过程中。在实验期间 (在同一个房间和黑暗循环中, 临时将老鼠转移到单个笼子里, 进行蔗糖和露天试验, 并在不同的房间和黑暗循环中进行强迫游泳试验, 并对其中的一个压力源 (指 2.1.7) 进行研究, 并将它们返回到ir 最初的社会团体在末端。</li>
</ol>2. 大鼠抑郁症的诱导程序
注: 为了诱发抑郁症, 将60只大鼠置于所暴露的组中, 对 as 的几种操作进行五周 20的操作。
<ol><li>以随机顺序将老鼠每天暴露在以下7种压力源中的 2;在白天和晚上的一个压力源, 连续5周。<ol>
<li>议院鼠在小组 (六个鼠, 而不是通常三, 每笼子为 18 h);</li>
		<li>把老鼠放在倾斜的笼子里 (沿垂直轴的45°为3小时);</li>
		<li>剥夺老鼠的食物 (18 小时);</li>
		<li>剥夺老鼠的水 (18 小时), 并将其暴露在水中后立即水剥夺 (1 小时) 的空瓶子;</li>
		<li>将大鼠放在潮湿的寝具笼中 (300 毫升的水洒在被褥中) 用于8小时 (夜间循环);</li>
		<li>每周两次暴露大鼠连续照明 (24 小时) 和反转光/暗循环 (12 小时);</li>
		<li>把老鼠放在炎热的环境中 (40°c, 5 分钟的周期), 另一种用来增加热量的器具。</li>
	</ol>
</li>
	<li>通过执行蔗糖首选项测试 (参见步骤 4) 来确认抑郁症的发展。 注意: 可以在上述每个步骤之后暂停该协议。此外, 如果任何异常行为是由任何鼠显示, 那么, 消除鼠和任何其他可能受到不规则鼠的影响的老鼠。</li>
</ol>3. 建立幼稚大鼠抑郁传染的程序
<ol><li>建立30个社会群体与大鼠从因暴露 (60) 和抑郁症传染 (30) 组:<ol>
<li>在30个不同的笼子里每个笼子里都有两只老鼠。</li>
		<li>将一只老鼠从抑郁症传染组中添加到每个笼中, 其中包含两个因暴露的老鼠。</li>
	</ol>
</li>
	<li>在标准条件下, 允许同居 5 周, 使用 "周和水可用" ad 随意。</li>
	<li>同居5周后, 按照图 1中显示的顺序, 将所有组按蔗糖首选项、打开字段和强制游泳测试进行分组。</li>
</ol>4. 蔗糖偏好测试21
<ol><li>在黑暗的循环中, 把老鼠放在与房屋相同的房间里的单个笼子里。</li>
	<li>将一瓶100毫升 1% (瓦特/v) 蔗糖溶液放在每个笼中24小时, 并允许适应。</li>
	<li>取出瓶子, 将食物和水的老鼠剥夺12小时。</li>
	<li>将两个瓶子, 一个包含100毫升蔗糖溶液 (1%, 瓦特/v) 和另一个, 100 毫升自来水, 在每个笼子里4小时。</li>
	<li>记录所消耗的蔗糖溶液和水的体积 (毫升), 并计算与蔗糖偏好的亲和力, 如下所示: <img alt="Equation 1" src="/files/ftp_upload/57137/57137eq1.jpg">
</li>
</ol>5. 野外试验
注: 标准的野外试验通常用于评估实验动物的运动、探索和焦虑行为, 以及对新奇事物的行为反应22, 23。此测试还显示为分析抑郁行为24。野外试验检验两个对立参数;啮齿类动物对明亮的光线在田野中心闪耀的恐惧, 反对他们对新奇事物的表达欲望。当焦虑时, 啮齿类动物往往避免发现和留在墙上 (thigmotaxis)。这种焦虑是由避免明亮的中心场的程度决定的。开放领域, 包括一个黑色的哑光丙烯酸盒 (120 厘米 x 60 厘米 x 60 厘米), 分为中心部分 (25%) 和其余的框 (75%)。这个测试发生在同一个房间里, 在房屋的黑暗周期。在该字段上方悬挂约200厘米的摄像机用于记录打开的字段测试22, 23。
<ol><li>在引进每种动物之前, 用5% 酒精清洗器具。把老鼠放在面对墙的开阔田野的拐角处。</li>
	<li>用摄像机记录老鼠的行为5分钟。</li>
	<li>分析以下参数的后记录: 总行程距离, 速度在现场的中心部分, 并在该领域的中心部分花费的时间。</li>
</ol>6. 强制游泳试验
注: 强迫游泳试验的原理是基于这样一个事实: 当老鼠被迫在密闭空间游泳时, 他们最终会放弃并保持静止, 偶尔移动身体以避免溺水21, 23。由于已经组装的仪器的艰巨性, 这个测试是在不同的房间进行的黑暗周期。
<ol><li>为适应, 将老鼠放在玻璃筒中 (100 厘米高, 直径40厘米, 40 厘米深), 含水在室温下, 用于15分钟的游泳时段。</li>
	<li>从钢瓶中取出老鼠, 用纸巾擦干, 放在温暖的笼子里15分钟。</li>
	<li>把老鼠还给它的家 (原) 笼; 注意: 协议可以在这里暂停。此外, 如果任何老鼠在这个测试过程中溺水, 立即拉出来。</li>
	<li>第二天, 录像一个5分钟的游泳会话, 并分析后记录的以下参数: 静止, 攀登和排便。</li>
</ol>

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?...

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。

<table><tbody><tr><td>Rat Cages</td><td>Techniplast</td><td>2000P</td><td>Conventional housing for rodents. Was used for housing rats throughout the experiment</td></tr><tr><td>Water</td><td>-</td><td>-</td><td>Common tap water used througout the experiment at different stages</td></tr><tr><td>Purina Chow</td><td>Purina</td><td>5001</td><td>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</td></tr><tr><td>Bottles</td><td>Techniplast</td><td>ACBT0262SU</td><td>150 ml bottles filled with 100 ml of water and 100 ml 1%(w/v) sucrose solution</td></tr><tr><td>Black lusterless perspex box</td><td>-</td><td>-</td><td>(120 cm &amp;times; 60 cm &amp;times; 60 cm), divided into a 25% central zone and the surrounding border zone</td></tr><tr><td>Video Camera</td><td>Canon</td><td>-</td><td>Digital video camera for high definition recording of rat behavior under open field test</td></tr><tr><td>Alcohol</td><td>Pharmacy</td><td>-</td><td>99% pharmaceutical alcohol diluted to 5% and used for lceaning the open field test box before the introduction of each rat</td></tr><tr><td>Glass cylinder</td><td>-</td><td>-</td><td>100 cm tall, 40 cm in diameter, and 40 cm deep cylinder used for carrying out the forced swim test</td></tr><tr><td>Paper towels</td><td>Pharmacy</td><td>-</td><td>Dry towels used for keeping rats dry after immersing them in water</td></tr><tr><td>Bold markers</td><td>-</td><td>-</td><td>Common bold markers used for labeling rats</td></tr></tbody></table>

a new method for inducing a depression-like behavior in rats

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。

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 ...

Watch this Scientific Journal Video about A New Method for Inducing a Depression-Like Behavior in Rats at JoVE.com

A New Method for Inducing a Depression-Like Behavior in Rats

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。

一种诱导大鼠抑郁症状行为的新方法

Contagious depression is a phenomenon that is yet to be fully recognized and this stems from insufficient material on the subject. At the moment, there is ...

a-new-method-for-inducing-a-depression-like-behavior-in-rats

Research

JoVE Journal

Behavior

20.8K 次观看.  Ben-Gurion University of the Negev. 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。

视频: A New Method for Inducing a Depression-Like Behavior in Rats

The Forced Swim Test as a Model of Depressive-like Behavior

The goal of the present protocol is to describe the forced swim test (FST), which is one of the most commonly used assays for the study of depressive-like behavior in rodents. The FST is based on the assumption that when placing an animal in a container filled with water, it will first make efforts to escape but eventually will exhibit immobility that may be considered to reflect a measure of behavioral despair. This test has been extensively used because it involves the exposure of the animals to stress, which was shown to have a role in the tendency for major depression. Additionally, the FST has been shown to share some of the factors that are influenced or altered by depression in humans, including changes in food consumption, sleep abnormalities and drug-withdrawal-induced anhedonia. The main advantages of this procedure are that it is relatively easy to perform and that its results are easily and quickly analyzed. Moreover, its sensitivity to a broad range of antidepressant drugs that makes it a suitable screening test is one of the most important features leading to its high predictive validity. Despite its appeal, this model has a number of disadvantages. First, the issue of chronic augmentation is problematic in this test because in real life patients need to be treated for at least several weeks before they experience any relief from their symptoms. Last, due to the aversiveness of the FST, it is important to take into account possible influences it might have on brain structure/function if brain analyses are to be carried out following this procedure.

This protocol describes the forced swim test, which is used for the study of depressive-like behavior in rodents. This procedure involves placing an animal in a container filled with water that eventually will lead to the exhibition of immobility behavior, which is considered to reflect behavioral despair.

在强迫游泳试验作为抑郁样行为的模型

The goal of the present protocol is to describe the forced swim test (FST), which is one of the most commonly used assays for the study of depressive-like ...

科研

行为学

Applying Stereotactic Injection Technique to Study Genetic Effects on Animal Behaviors

Stereotactic injection is a useful technique to deliver high titer lentiviruses to targeted brain areas in mice. Lentiviruses can either overexpress or knockdown gene expression in a relatively focused region without significant damage to the brain tissue. After recovery, the injected mouse can be tested on various behavioral tasks such as the Open Field Test (OFT) and the Forced Swim Test (FST). The OFT is designed to assess locomotion and the anxious phenotype in mice by measuring the amount of time that a mouse spends in the center of a novel open field. A more anxious mouse will spend significantly less time in the center of the novel field compared to controls. The FST assesses the anti-depressive phenotype by quantifying the amount of time that mice spend immobile when placed into a bucket of water. A mouse with an anti-depressive phenotype will spend significantly less time immobile compared to control animals. The goal of this protocol is to use the stereotactic injection of a lentivirus in conjunction with behavioral tests to assess how genetic factors modulate animal behaviors.

Stereotactic injection of lentiviruses expressing cDNAs or shRNAs can modulate gene expression in specific brain areas of mice. Here, we present a protocol to combine stereotactic injections with behavioral tasks, such as the Open Field Test (OFT) and the Forced Swim Test (FST).

应用立体定向注射技术在研究动物行为的遗传效应

Stereotactic injection is a useful technique to deliver high titer lentiviruses to targeted brain areas in mice. Lentiviruses can either overexpress or ...

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 ...

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 Complex Diving-For-Food Task to Investigate Social Organization and Interactions in Rats

For many species, where status is a vital motivator that can affect health, social hierarchies influence behavior. Social hierarchies that include dominant-submissive relationships are common in both animal and human societies. These relationships can be affected by interactions with others and with their environment, making them difficult to analyze in a controlled study. Rather than a simple dominance hierarchy, this formation has a complicated presentation that allows rats to avoid aggression. Status can be stagnant or mutable, and results in complex societal stratifications. Here we describe a complex diving-for-food task to investigate rodent social hierarchy and behavioral interactions. This animal model may allow us to assess the relationship between a wide range of mental illnesses and social organization, as well as to study the effectiveness of therapy on social dysfunction.

This protocol describes a method of examining social hierarchy in a rat model. Rats perform a complex diving-for-food task in which they form a distinct hierarchy according to their willingness to dive underwater and swim to obtain a food pellet. This method is used to understand decision making and social relationships among highly social animals in small groups.

调查大鼠社会组织和互动的复杂潜水换食物任务

For many species, where status is a vital motivator that can affect health, social hierarchies influence behavior. Social hierarchies that include ...

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. ...

Developing a Rat Model for Bipolar Disorder

Bipolar disorder is a mental health condition characterized by extreme mood swings, including periods of emotional highs (mania) and lows (depression). While the exact underlying neurobiology is not yet fully understood, imbalances in neurotransmitter systems, particularly dopamine, appear to play a central role. For this reason, manipulations of dopaminergic pathways have been used to model mania or depression in rodents. However, models that accurately represent the typical switch between these two episodes are rare, limiting face validity. In a unique model, modern techniques are used to temporarily increase dopamine D1 receptor expression, which has been implicated in the pathology of bipolar disorder. A tetracycline-inducible lentiviral construct that expresses the dopamine D1 receptor under the control of the calmodulin kinase II alpha promoter is stereotactically injected into the medial prefrontal cortex of adult rats. Dopamine D1 receptor overexpression is achieved by adding the tetracycline analog doxycycline to the animals&#39; drinking water, leading to an increase in reward-related, impulsive, and risk-taking behaviors and a decrease in anxiety. These behaviors resemble a mania-like phenotype. By removing doxycycline from the drinking water, a depressive-like phenotype, characterized by increased helplessness and anhedonia, can be induced within the same animal. This article provides a step-by-step protocol for performing the surgery, as well as procedures for inducing the bipolar disorder-like phenotype. Additionally, considerations for assessing behavioral changes associated with mania-like and depressive-like behavior are described. This promising model, which demonstrates good construct and face validity, offers a valuable tool for further investigating the pathophysiological mechanisms of bipolar disorder.

This article presents a protocol for the induction of a unique rat model of bipolar disorder that captures both mania-like and depressive-like behavior.

开发双相情感障碍的大鼠模型

Bipolar disorder is a mental health condition characterized by extreme mood swings, including periods of emotional highs (mania) and lows (depression). ...

Sucrose Preference and Novelty-Induced Hypophagia Tests in Rats using an Automated Food Intake Monitoring System

The prevalence and incidence of depressive disorders are rising worldwide, affecting about 322 million individuals, underlining the need for behavioral studies in animal models. In this protocol, to study depression-like and anhedonic behavior in rats, the established sucrose preference and novelty-induced hypophagia tests are combined with an automated food and liquid intake monitoring system. Prior to testing, in the sucrose preference paradigm, male rats are trained for at least 2 days to consume a sucrose solution in addition to tap water. During the test, rats are again exposed to water and sucrose solution. Consumption is registered every second by the automated system. The ratio of sucrose to total water intake (sucrose preference ratio) is a surrogate parameter for anhedonia. In the novelty-induced hypophagia test, male rats undergo a training period in which they are exposed to a palatable snack. During training, rodents show a stable baseline snack intake. On test day, the animals are transferred from home cages into a fresh, empty cage representing a novel unknown environment with access to the known palatable snack. The automated system records the total intake and its underlying microstructure (e.g., latency to approaching the snack), providing insight into anhedonic and anxious behaviors. The combination of these paradigms with an automated measuring system provides more detailed information, along with higher accuracy by reducing measuring errors. However, the tests use surrogate parameters and only depict depression and anhedonia in an indirect manner.

Presented here is a protocol to study depression-like and anhedonic behavior in rats. It combines two well-established behavioral methods, the sucrose preference and novelty-induced hypophagia tests, with an automated food and liquid intake monitoring system, to indirectly investigate rodent behavior using surrogate parameters.

使用自动食物摄入量监测系统对大鼠的蔗糖偏好和新奇诱导性低吞咽测试

The prevalence and incidence of depressive disorders are rising worldwide, affecting about 322 million individuals, underlining the need for behavioral ...

医学

<meta charset="utf8"></head><body>约束压力对啮齿动物模型中生理学和神经生物学的影响

Restraint to Induce Stress in Mice and Rats

Across all animal species, exposure to stressful conditions induces stress responses. One method to study the effects of stress using rodent models is the restraint stress procedure. Restraint stress has been used for decades to investigate changes in physiology, genetics, neurobiology, immunology, and other systems impacted by stress. Due to the ease of performing the procedure, low cost, and numerous modifications to scale for the intensity and duration of stress exposure, a vast literature of studies has used restraint stress in mice and rats. As one example, this study presents previously published data showing the impact of restraint stress in transgenic mice on plasma corticosterone levels and optogenetically-induced norepinephrine release. Acute restraint stress increased plasma corticosterone levels, yet this effect was blunted in mice following repeat restraint stress. However, stimulated norepinephrine release in the bed nucleus of the stria terminalis was increased only in the repeat restraint stress group. These data highlight important considerations of restraint parameters on dependent measures. Additional descriptions of restraint stress in rats are also included for comparison. Finally, the influence of the parameters of the restraint (e.g., acute vs. chronic) and characteristics of the animal subjects (strain, sex, age) are discussed.

<meta charset="utf8"></head><body>约束以诱导小鼠和大鼠的压力

This article covers the procedures to induce stress responses using physical restraint stress in mice and rats. Additional considerations that should be observed when selecting and using restraint stress in rodent models are discussed.

约束以诱导小鼠和大鼠的压力

Across all animal species, exposure to stressful conditions induces stress responses. One method to study the effects of stress using rodent models is the ...