西尔维亚克卢捷、梅根 LaFollette、安娜 Gaskill 和鲁思纽贝里希望把这篇文章献给我们敬爱的合著者 Jaak Panksepp 的记忆, 在完成这份手稿的最后阶段去世。我们怀念 Jaak 的 "老鼠之父"--他对动物情感的洞察, 形成了这项工作的基本灵感。这份材料部分是根据华盛顿州立大学兽医暑期研究奖学金、动物福利研究所的动物福利增强奖以及美国 "实验室动物科学补助金" 所支持的工作。实验室动物科学协会。这篇文章的出版是由圣迭戈佩科球场动物用品公司赞助的。我们要感谢卡罗尔和普渡大学的实验动物计划, 让我们为拍摄的老鼠挠痒痒。

所有实验都是按照国家卫生研究院的规定进行的, 用于对实验室动物的护理和使用31,32在 AAALAC 国际认证的设施, 并经华盛顿州批准。大学机构动物保育和使用委员会。下面的协议可以将人员暴露给实验室动物过敏原。个人防护设备应按照机构职业健康和安全计划和卫生保健提供者的建议佩戴。该议定书描述了典型的实验室住房条件下的程序, 但可适用于更高生物安全设施 (例如使用安全柜等)。
1. 设备的准备和安装
<ol><li>装卸箱<ol>
<li>准备一个动物的家庭笼子或其他围栏的发痒, 此后称为处理箱。</li>
		<li>确保这个搬运箱足够大, 可以为你的挠手提供空间, 让老鼠在防止它们跳出的时候四处走动。</li>
		<li>确保装卸箱没有障碍物。因此, 如果在家庭笼中进行发痒, 删除任何对象, 如小屋, 啃枝, 皱纹纸。</li>
		<li>用床上用品33对处理箱地板进行排队。其他类型的软地板覆盖可以使用, 但不一样有效的诱发50赫发声13。</li>
		<li>将处理箱放在表或工作台的高度, 使处理程序的手舒适地到达处理箱的整个楼层面积。</li>
		<li>如果需要, 将大鼠 habituating 到处理盒前, 尽量减少新奇的效果。</li>
	</ol>
</li>
	<li>计时器: 为了表示十五年代回合的开始和结束, 在处理盒附近放置一个定时装置, 在那里可以很容易地阅读。另外, 听觉时间信号也可以通过耳机传送到笔记本。</li>
	<li>发声记录<ol>
<li>如果正在记录发声以量化不同的发声类型为研究目的, 使用麦克风能够捕获10-120 赫宽带声音, 连接到一个设备能够记录高频率的声音。</li>
		<li>将麦克风挂起或贴在盒子的顶部或一侧, 足够低, 以清楚地检测到呼叫, 避免在附近笼子里的老鼠的叫声引起混淆, 但在老鼠身体接触不到的情况下。</li>
		<li>如果发声只需要监测, 以确认正确的发痒技术, 然后使用蝙蝠探测器, 并设置它在框的一侧。如果使用简单的外差检测器, 请将该设备设置为50赫。</li>
	</ol>
</li>
	<li>实验室手套: 发痒时使用裸露或薄手套的手。挠痒技术是用徒手开发的。 然而, 一只薄薄的戴手套的手也能有效地诱导嬉戏行为和50赫 USV 的生产, 同时允许处理者感觉到大鼠体内的压力量, 并通过手套感受到老鼠的反应。</li>
</ol>2. 发痒做法
<ol><li>如果需要, 戴上实验室手套。把家庭笼子带到桌子或工作台上。如果不在主笼中进行发痒, 将老鼠轻轻地转移到搬运箱中。启动计时器, 如果需要, 音频录制。</li>
	<li>为一致的应用, 十五年代之间的手接触和十五年代发行从联络一共2分钟交替。这种相互作用的持续时间已被发现足以增加老鼠对人类的吸引力11。<ol>
<li>要开始与十五年代版本的发痒会话, 请将手一动不动地放在处理箱的一侧。手的存在使得老鼠可以通过对手进行舔和轻咬 (小点心) 来寻求相互作用, 这表明老鼠有兴趣互动22。当这种情况发生时, 把手从老鼠身上移开, 这可以吸引老鼠嬉戏地追逐手。或者, 在十五年代的发行版中, 把手放在盒子里。</li>
		<li>跟随释放与十五年代的发痒, 开始与背部接触 (2-4 s) 的互动。使用一只手, 有力地触摸老鼠的颈背 (颈部背面) 与指尖使用快速手指运动通常执行的人发痒。避免与臀部接触, 因为在攻击性遇到34期间, 身体的这个区域是目标。</li>
		<li>用大头针跟踪背侧接触。将拇指和中指放在大鼠的前腿下;抬起老鼠, 只要足够高, 就能让老鼠在它的背部迅速转动, 同时确保尾巴不会得到纠结。 注意: 在老鼠背上转动老鼠时, 用小指轻轻地推鼠背部可能有帮助。</li>
		<li>松散地抱住老鼠, 但牢牢地抓住它;要有主见, 但不能强硬。一旦老鼠的背部在地板上, 保持身体松散, 而移动手指迅速和有力, 但轻轻地在腹部, 因为是通常使用的人发痒。</li>
		<li>即使刺激是快速和果断, 保持固定轻快 (2-4 s/针), 以尽量减少负面反应。允许鼠右自身, 并迅速跟随背部接触。</li>
		<li>继续交替在背部接触和别针之间。平均来说, 应该有4到 5 pins/15 的35。</li>
		<li>不要用双手把老鼠捡起来。在十五年代的发痒, 总是保持手指移动和接触鼠的身体, 甚至在转折之间的针脚和背部接触。</li>
		<li>执行三个额外的 15 s 的痒和 15 s 的发行共计2分钟。</li>
	</ol>
</li>
	<li>如果使用一个搬运箱, 把老鼠送回其主笼。如果使用家庭笼子, 把浓缩物放回笼子里。用纸巾清洁搬运箱, 除去被褥不吸收的粪便和尿液。</li>
	<li>根据需要重复与下一笼鼠。</li>
</ol>3. 同时挠多只老鼠
<ol><li>老鼠可以被胳肢为组36。如果处理时间不相关, 交替发痒每鼠十五年代。发痒会话的持续时间可以根据需要延长2分钟以上, 以便每只老鼠收到四次的发痒手接触散置释放。</li>
	<li>如果处理时间与研究结果相关, 则使用以下过程:<ol>
<li>为对, 发痒一只老鼠十五年代紧接着由发痒第二只老鼠为下个十五年代 (i. e., 在第一只老鼠的发行期间), 等等。这个难题没有休息期。</li>
		<li>对于三胞胎, 使用3.2.1 中描述的过程, 使两个大鼠发痒, 同时用另一只手挠第三个老鼠。</li>
		<li>对于4或更多的老鼠群, 在十五年代为每只老鼠或一对老鼠挠痒痒。发痒会话的持续时间可以根据需要延长2分钟以上。</li>
	</ol>
</li>
</ol>

作者声明他们没有什么可透露的。

本协议描述了一种大鼠发痒的技术, 一种模拟大鼠粗糙和翻滚的游戏行为的有趣的处理技术, 它在处理大鼠时能有效地生成发声指示阳性影响和增加方法行为。用于公共畜牧业或医疗和研究程序, 如 IP 注入。
社交游戏, 一种典型的积极的社会接触形式, 已被建议帮助校准的情绪反应的可怕的情况下42,43, 并产生弹性的焦虑和抑郁症44。通过模仿老鼠的社交游戏, 发痒似乎有同样有益的效果7。因此, 对于瘙痒的应用成功地诱导积极的情感状态, 重要的是要记住, 手是打算作为 "戏剧伙伴" 在发痒。手是有吸引力的, 因为它模拟的行为, 老鼠期待和享受从另一只老鼠在粗糙和翻滚的游戏。因此, 用双手举起和握住老鼠并不模仿老鼠玩耍, 也可能没有同样的效果。事实上, 实验鼠将学会避免非嬉戏的限制, 其中一个处理者用一只手握住它们, 然后用另一只手抚摸它们45。在老鼠发痒的过程中, 在活泼和俏皮的同时, 自信而果断地移动手也是很重要的。保持固定轻快 (2-4 s/针) 应尽量减少负面反应, 因为在大鼠之间的颠簸和翻滚发挥, 反复钉住导致说出22赫 USVs18。
即使幼鼠更顽皮, 并显示更强烈的反应比成年大鼠发痒18, 成年时发痒也有好处10。小鼠在年轻的时候也被发现在生活中有好处36, 提示老鼠对他们对人类存在的情绪反应有长期的积极影响。对瘙痒反应的性别差异是不一致的, 报告没有性别差异的小鼠46,47, 青少年男性产生更多50赫发声和较少22赫发声比少年女性29 ,48,39, 和年长女性产生更多50赫发声比相同年龄的男性29, 类似的发现为社会戏剧49。
利用大鼠的运动模式和发声能力, 可以评估瘙痒技术的有效性。老鼠将咬和舔处理者的手指在15秒的释放时间后, 发痒11。小鼠是轻的, 无伤害性的叮咬被描述作为引诱行为在幼小老鼠22。当处理程序将手移到处理盒上时, 老鼠会跟随并追逐它。老鼠, 特别是年轻的, 也会跑, 围绕着在发痒回合之间的盒子, 并显示一个明显增加的活动后, 发痒回合, 类似的运行活动, 特点是粗糙和翻滚的游戏。如果老鼠在释放过程中保持静止不动, 可能需要调整发痒技术, 例如减少 pin 持续时间或给出更少的针脚。最好给第一个发痒会话的短时间针。当大鼠习惯于发痒时, 可以增加针的持续时间和数量。老鼠发出50赫 USVs, 包括颤音, 在发痒和发痒的回合之间。在稳定47之前, 在每日发痒的前两周, 可以看到在15秒的版本中生成的颤音的数量逐渐增加。个体差异使发痒的老鼠被分成高和低的呼叫者, 响应不同的压力, 焦虑和快感缺失 46, 47, 50.
在挠性13期间, 通过50赫 USVs 的生产, 成功地利用大鼠发痒诱发阳性影响。它最近被实施了作为一种技术减少对人的恐惧在老鼠和减轻他们的 aversiveness 医学和研究规程例如注射。有证据表明, 如果每只动物每天只提供2分钟的时间, 发痒是一种有效和实用的方法来减少人类的避免11。考虑到幼鼠将一起玩约60分钟每天51,52,53, 每天发痒2分钟是切实可行的, 但可能过于简短, 以复制整个社会发挥作用的大鼠。宠物鼠主人, 通常有更多的时间来处理他们的老鼠比实验室管理员, 可能会提供额外的痒鼠, 只要老鼠继续积极反应。基于布格道夫将军 et. 44,45, 前15分钟的粗略和翻滚的游戏似乎是最积极的老鼠。反过来, 在长达15分钟的时间里, 对老鼠进行挠痒可能会更有效, 特别是如果有正当理由不能将它们保存在一个社会群体中。但是, 基于 "意外"38的 "培训", 可能需要比此处描述的方法更多样的技术来维护较长的发痒会话的趣味性。只要其他生物学上重要的活动, 如睡眠和喂养不受损, 每天额外的发痒疗程也可能是有益的。除了有助于改善实验室和宠物大鼠的福祉, 所描述的标准化发痒技术还可用于持续研究, 目的是了解社会游戏及其组成部分对行为、社会和大脑的影响。发展。
当周围注射时发痒, 特别是与以前的发痒经验 (结束40-50 天前), 它增加了50赫 USV 率在注射之前和之后, 并减少了在注射过程中的声音呼叫率10.因此发痒似乎减轻了 IP 注射的不良影响, 特别是在习惯于发痒为青少年的老鼠10。即使发痒没有防止与注射有关的不适, 根据发声呼叫的生产评估, 它增加了50赫 USVs 相比, 控制条件, 之前, 期间和之后的克制程序12。根据50赫 USV 数据, 应用发痒的最有效时间点就在之前, 而不是在约束过程12之后。在注射前发痒的老鼠在过程中有一个结转效应, 提高了阳性的影响12。因此, 发痒可以减少常规医疗程序对大鼠福利和行为的潜在负面影响。需要进行更多的研究, 以确定该技术如何与其他注射技术和其他医疗/实验程序有效配对。
总的来说, 我们已经证明, 老鼠发痒导致积极的结果, 如增加生产的50赫 USV 和接近行为, 以及减少人避免和抵抗处理。我们建议鼠痒作为一种可行的方法来改善大鼠福利和建模积极的情感状态。

在实验室和宠物中饲养的小动物, 如家养老鼠 (鼠褐) 可以导致压力的行为和生理指标的显著增加1, 以及厌恶反应暗示情绪困扰2。处理老鼠可以触发基于恐惧的反应对人3,4, 这可能使进一步处理更加困难, 增加损伤的动物和处理者的风险, 并且限制实验数据5的有效性。
为了避免处理对实验结果和人与动物关系的负面影响, 在将新获得的幼兽分配给实验性治疗之前, 允许一些时间习惯人类的相互作用是常见的做法。在这一驯化期间, 看护者可能会将老鼠暴露在一系列可以在形式和持续时间上高度可变的事件中。这些可能包括被动接触人, 接触, 解除, 爱抚, 举行, 交谈, 并提供食物款待。虽然报告了这些程序的组合, 以减少对人类的恐惧6, 但目前还不清楚哪些具体做法最有效, 由忙碌的动物看护者使用。有报告说, 老鼠可能有任何负面反应, 或至少没有有利的反应, 一些这些个别技术2,7,8,9。
相比之下, 丰富的证据支持这样的结论, 即挠痒, 一种模仿老鼠嬉戏的粗糙和翻滚行为方面的处理技术, 是一种强有力的社会接触形式, 特别是对于幼年大鼠10, 11,12,13。老鼠是高度社会哺乳动物, 从观察他们花费的时间作为少年14和他们的强烈动机重建和维护社会联络与 conspecifics15,16, 是清楚的; 17。大鼠发痒利用大鼠嬉戏的社会本性将处理转化为一种积极的体验。这一概念最初是作为一个模型, 以调查社会游戏行为诱发的积极情感状态的神经生物学基础7。从那以后, 老鼠发痒被使用了在56个不同的实验, 22 比较发痒到其他处理技术13。
大鼠的粗糙和翻滚游戏的特点是两个关键行为: "背接触" 和 "pin" (图 1)18,19。在颠簸和翻滚的游戏中, 一只老鼠开始通过与伴侣的背颈进行背部接触来发挥作用。收件人通过滚动仰卧进行响应, 并由站在19以上的启动器固定。该剧继续与老鼠轮流在每个位置, 在顶部和下面的18。人类的处理者可以模仿的两个关键组成部分的粗糙和翻滚发挥通过交替接触的大鼠的颈背 (背部接触) 和腹面 (针) 使用剧烈, 快速移动的手指类似于那些在发痒的儿童。当然, 发痒不是大鼠粗糙和翻滚游戏的确切副本, 因为老鼠在发痒的时候不能把人的手钉在身上。实际上, 个人在粗糙和翻滚的游戏和发痒中的参与程度可以不同20,21。尽管如此, 在 conspecifics 中, 发痒似乎还是与粗糙和翻滚的游戏同样具有同样的奖励机制。发痒是由动物积极征求, 并可以作为一个奖励的操作性学习, 贡献的证据, 被胳肢是极大的奖励年轻的老鼠7,11,12,13,22. 即使老鼠也被报告学习一项操作性的任务, 以换取温柔的抚摸作为奖励, 他们比抚摸7更快速地接近提供发痒的人的手。
在发痒中使用的针脚似乎类似于常见的约束程序, 但有证据表明, 老鼠认为这些类型的处理方式不同。当老鼠被反复抑制, 如注射过程, 他们分泌过量的卟啉导致 chromodacryorrhea ("红眼泪")8。Chromodacryorrhea 发生在反应急性压力, 使皮肤和毛皮周围的眼睛和鼻子变成染红颜色23。当被反复按住和约束在背部像在一个别针, 老鼠显示对人类的吸引力比当胳肢12。这些结果意味着在发痒过程中重复的短暂限制和释放被认为不同于非嬉戏的克制。因此, 在发痒中使用的精确技术对于产生一个积极的情感状态, 而不是为处理压力作出贡献具有重要的意义。
观察瘙痒对大鼠情感状态的影响, 可以很容易地完成对大鼠的发声。大鼠通常产生两类超声发声 (USVs), 在大约22赫和50赫, 除了发声发声。22赫 USVs 通常发生在预测厌恶事件, 并伴有高脑胆碱能活动24。因此, 22 赫 USVs 被认为表示焦虑的负面情绪状态。50赫 USVs, 特别是调频 "颤音" 类型 (图 2), 通常与奖励情况和刺激有关, 并伴有增加的脑多巴胺活动24,25。因此, 丰富的50赫 USVs 的表达式被认为反映了一个积极的情感状态24,26,27,28。最后, 发声发声通常与之相关, 因此用作身体疼痛和不适的标志。因此, 这三种发声方式的差异性生产提供了一个可靠的记录, 改变了老鼠的情感状态26。老鼠在接触掠食者时会产生 USVs, 大约22赫, 暴露于疼痛刺激, 如足部休克和男性间战斗28。还有报道说, 在天真的老鼠中, USVs 有多个22赫的小鼠, 推断为表示负面影响2。相比之下, 当与其他大鼠进行粗糙和翻滚的玩耍时, 老鼠会产生大量的50赫 USVs。因此, 50 赫 USVs 的速率提供了由发痒2930生成的正情感响应的分级度量。
现有的 "如何挠老鼠" 的描述是相当简短的, 可能导致可变的结果。此外, 新手 "老鼠屁" 可能是过于试探性的尝试, 试图模仿粗糙和翻滚的游戏。"挠痒痒" 这几个字在视觉上表现得更容易理解。因此, 本文的目的是提供一个详细的描述和示范, 如何模仿老鼠的积极嬉戏互动的有效和一致的方式, 可靠地引起的积极反应, 大多数大鼠处理。该协议描述了一个标准化的发痒技术, 并解释如何发痒可以结合的过程, 如克制和注射, 以减轻潜在的不愉快的情感体验。

<table border="0" cellpadding="0" cellspacing="0" width="1252">
	<tbody>
		<tr height="20">
			<td height="20" style="height:20px;width:451px;">Table or workbench</td>
			<td style="width:93px;"></td>
			<td style="width:468px;"></td>
			<td style="width:241px;">No specific brand is recommended.</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:451px;">Handling box (rat home cage or another enclosure)</td>
			<td style="width:93px;"></td>
			<td style="width:468px;"></td>
			<td style="width:241px;">No specific brand is recommended.</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:451px;">Bedding or or other type of soft cover</td>
			<td style="width:93px;"></td>
			<td style="width:468px;"></td>
			<td style="width:241px;">No specific brand is recommended.</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;width:451px;">Gloves (thin laboratory gloves)</td>
			<td style="width:93px;"></td>
			<td style="width:468px;"></td>
			<td style="width:241px;">Optional.</td>
		</tr>
		<tr height="80">
			<td height="80" style="height:80px;width:451px;">Timing device</td>
			<td style="width:93px;">Deltaworks</td>
			<td style="width:468px;">Interval Timer:Timing for HIIT Training, Workouts 
			https://itunes.apple.com/us/app/interval-timer-timing-for-hiit-training-workouts/id406473568?mt=8</td>
			<td style="width:241px;">Optional. Any timer will do, although it is convenient to use an interval timer if you are tickling multiple rats.</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:451px;">Ultrasonic microphone such as a bat detector or USB microphone</td>
			<td style="width:93px;">Magenta Electronics LTD</td>
			<td style="width:468px;">Bat4 Bat Detector 
			https://www.magenta2000.co.uk/acatalog/Bat_Detector_Bat4.html</td>
			<td style="width:241px;">Optional. The Magenta bat detector is relatively inexpensive and easy to use, but can only detect vocalizations at one range at a time.</td>
		</tr>
		<tr height="80">
			<td height="80" style="height:80px;width:451px;"></td>
			<td style="width:93px;">Dodotronic</td>
			<td style="width:468px;">Ultramic 200K 
			http://www.dodotronic.com/ultramics/?v=7516fd43adaa</td>
			<td style="width:241px;">Optional. This microphone has worked well in our experiments. There are many other options for ultrasonic microphones.</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:451px;">Bioacoustic software</td>
			<td style="width:93px;">CIBRA</td>
			<td style="width:468px;">SeaWave 
			http://www-3.unipv.it/cibra/seawave.html</td>
			<td style="width:241px;">Optional. Free software with limited recording capabilities.</td>
		</tr>
		<tr height="120">
			<td height="120" style="height:120px;width:451px;"></td>
			<td style="width:93px;">CIBRA</td>
			<td style="width:468px;">SeaPro 
			http://www-3.unipv.it/cibra/seapro.html</td>
			<td style="width:241px;">Optional. This software has extensive recording capabilities, and has worked well in our studies. There are many other software packages that work with bioacoustic microphones.</td>
		</tr>
	</tbody>
</table>

tickling, a technique for inducing positive affect when handling rats

处理像老鼠这样的小动物会导致一些不良影响。这些包括对人类的恐惧, 对处理的抵抗, 增加动物和他们的手的伤害风险, 减少动物福利和较少有效的研究数据。为了尽量减少对实验结果和人与动物关系的负面影响, 研究动物往往习惯于被处理。然而, 习惯的方法是高度可变的, 而且往往效果有限。更完全的是, 人类有可能模仿动物在搬运过程中嬉戏的粗糙和翻滚行为的各个方面。当系统地应用于实验鼠时, 这种顽皮的处理, 称为发痒, 始终如一地产生积极的行为反应。本文提供了一个标准化的大鼠发痒技术的详细描述。这种方法有助于今后对动物的积极情感状态的调查, 使其更容易处理普通畜牧业活动, 如网箱改变或医疗/研究程序, 如注射, 并作为一个来源实施社会充实。结果表明, 该方法可有效、实用性地减少大鼠恐惧, 改善其福利, 并能可靠地模拟阳性情绪状态。

影响或可能影响瘙痒响应的因素在表 1中进行了总结。多项措施对大鼠的福利和积极的影响表明, 大鼠发痒的阳性结果。常见的发现包括增加50赫 USVs 的产量, 提高方法的行为, 并提高处理的方便性。报告的大鼠发痒的基因和细胞水平的影响包括改变基因表达在下丘脑37和增加神经发生在海马的齿状回的38,39。结果表明, 减少了普遍的焦虑和恐惧的人也报告, 如减少延迟到接近9种不同的实验13, 更少的冻结后, 恐惧调理40,41, 并增加了条目入开放领域竞技场的中心由单独地被安置的老鼠36。有关详细信息, 请参阅 LaFollette et, 他们对发痒文献进行了系统的回顾, 其中列出了22份调查老鼠发痒结果的报告, 与其他技术13比较。
接下来, 简要的例子, 可以得到的结果, 当发痒技术是配对与克制和腹膜内 (IP) 注射程序。
大大鼠 (雄性; 85-94 天); n = 48) 在 IP 盐水注射前后2分钟内立即胳肢10天, 特别是与青少年发痒经验结合 (2 分钟/天从25-45 天), 产生更多的50赫 USV 只是之前 (GLM 方差分析, F3, 44 = 9.59, p < 0.0001;图 3A)后 (F3, 44 = 8.74, p = 0.0001;图 3B)注射 (Tukey-克莱默, p < 0.05) 与暴露于被动手10的大鼠相比。在实际的注射过程中, 对50赫 USVs 的生产进行了抑制 (平均值, 15, 1.4 USVs/分钟), 处理处理对其速率10没有影响。它的结论是, 发痒, 当应用在注射程序之前和之后, 诱导了一个积极的情感状态, 减轻了 aversiveness 的程序, 特别是那些已经暴露在发痒作为青少年。
为了找出如果在注射之前或之后减少瘙痒是否有效, 如果是这样的话, 哪个时间会更好, 对注射前、后和后的老鼠的反应进行比较。50赫 USVs 和可听见的呼叫率分别被测量为正面和负面影响的指示器, 各自12。大大鼠 (男性; 32-41 天; n = 96) 被限制, 并给予每日 IP 盐水注射 (注射) 或克制, 而不接受注射液 (控制, 对照), 并暴露在以下治疗之一: 不痒, 大鼠不在克制的做法之前和之后接触了 (TN);在 (TB)、后 (TA)、或前后 (TBA) 约束12之前和之后胳肢2分钟。在克制之前的2分钟, 在克制之前接受发痒治疗的老鼠 (TB, TBA) 产生了最50赫 USVs (GLMM 方差分析, F388 = 49.19, p < 0.0001;图 3C)。TA 和 TN 大鼠在抑制过程前的 USVs 率上没有差异。在手术过程中, 任何接受瘙痒的老鼠 (TA、结核、TBA) 产生的 USV 比未胳肢的大鼠多50赫 (TN;F388 = 50.67, p < 0.0001;图 3D)。在发痒的老鼠之中, 那些接受发痒在做法之前 (TB, TBA) 在克制期间产生了更多50赫 USVs 比那些以后发痒 (TA;p < 0.05)。在手术后的2分钟内, 所有发痒组 (TA、结核、TBA) 的大鼠产生的比未被胳肢的多50赫 USVs (TN;F388 = 53.64, p < 0.0001;图 3E)。此外, 在手术过程中, 老鼠在克制前发痒 (结核病, TBA) 比没有接受瘙痒的老鼠产生更少的发声呼叫, 而老鼠发痒之后 (TA) 与其他组中的大鼠没有区别 (F388 =3.67, p= 0.02;图 3F)。结果表明, 发痒大鼠之前, 抑制他们为 IP 注射产生了更大的积极影响的迹象, 在过程之前, 期间和之后的时间比发痒后, 只有克制12。
看护者对大鼠进行了以下处理治疗 (大男性; n = 32) 从57岁到74天: (1) 每周一次在笼子改变时最少处理一次;(2) 每日2分钟接触被动手;(3) 每天2分钟发痒, 模仿社会戏剧;(4) 对大鼠背部进行2分钟的克制, 模拟 unreciprocated 钉住的主要11。在 IP 注入后的一分钟内, 从发痒和被动治疗中的老鼠花更多的时间饲养在笼子的前半部分, 靠近研究员站立的地方, 与小鼠和克制的治疗相比 (GLM 方差分析, F3, 27= 5.70, p = 0.004;图 3G)。此外, 在人的方法测试中, 当暴露于一只熟悉或不熟悉的手3分钟时, 胳肢鼠发出的50赫 USVs 比老鼠在被动治疗中多出一只 (对数变换的平均值, 最小值: 0.7 @ 0.26, 被动: 0.6 @ 0.18, 胳肢: 1.8 @ 0.30,克制: 1.4 ~ 0.28;F328 = 4.04, p = 0.02)。因此, 被动手的简单存在帮助大鼠对人类的适应相对极小的处理, 但发痒是最有效的方法为对人产生正面反应11。
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/57190/57190fig1.jpg"> 图 1: 大鼠粗糙和翻滚的播放行为.(A) 背向接触;(B) Pin18。<a href="https://cloudflare.jove.com/files/ftp_upload/57190/57190fig1large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/57190/57190fig2.jpg"> 图 2: 调频 "颤音" 类型的50赫超声波发声.五的颤音发声在1秒内由一只老鼠在发痒中产生。17-、25和70赫的水平线是由室内的电子设备 (e. g) 生产的, 即计算机、麦克风、照相机。
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/57190/57190fig3.jpg"> 图 3: 在实验过程中, 或与腹腔内 (IP) 注射术前接触的老鼠的反应.在注射程序后 (B) 在成人后生成的50赫 USVs (A) 的速率 (平均 * SE 调用/分钟) 雄性大鼠暴露于最小处理 (M) 或发痒 (t) 作为青少年和被动手 (P) 或发痒 (t) 立即前后注射 (产量四治疗组合: m-p, t p, m t, t t);从克卢捷et 。10. 以前生成的50赫 USVs (均为 SE 呼叫/分钟) 的速率 (C), (D) 期间和 (E) 在克制 (有或没有 IP 注射) 以后每天连续10天由未接受发痒的少年雄性老鼠 (TN) 或瘙痒前 (TB), 后 (TA), 或前后 (TBA) 的程序;和 (F) 在克制期间产生的发声率;从克卢捷et 。12. (G) 持续时间 (平均约 SE) 在研究员附近养育在1分钟以后在被暴露对小, 被动, 发痒或克制处理的雄性老鼠的 IP 注射之后;从克卢捷et 。11. 带有不同字母 (a、b、c) 的条形图表示成对比较 (Tukey-克莱默、 p < 0.05) 的差异。<a href="https://cloudflare.jove.com/files/ftp_upload/57190/57190fig3large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always"><tbody>
<tr>
<td>因素</td>
			<td colspan="4">影响</td>
			<td>引用</td>
		</tr>
<tr>
<td>内在</td>
			<td colspan="4"></td>
			<td></td>
		</tr>
<tr>
<td>年龄</td>
			<td colspan="4">50赫超声发声 (USVs) 在24-44 和89-92 天龄大鼠间无差异</td>
			<td>18, 29, 42</td>
		</tr>
<tr>
<td></td>
			<td colspan="4">从71天到148天大鼠50赫 USVs 的减少</td>
			<td>29</td>
		</tr>
<tr>
<td></td>
			<td colspan="4">17天老男性做了许多50赫 USVs 比7-9 月老男性</td>
			<td>43</td>
		</tr>
<tr>
<td></td>
			<td colspan="4">大鼠发痒, 因为青少年和成人显示最积极的结果相比, 老鼠只痒作为青少年或成人。</td>
			<td>10</td>
		</tr>
<tr>
<td>性</td>
			<td colspan="4">雄性大鼠在44和71天大的时候产生了更多的50赫 USVs, 但雌性在148天内产生了更多的50赫 USVs。</td>
			<td>29</td>
		</tr>
<tr>
<td></td>
			<td colspan="4">雄性大鼠在44和58天产生的 USVs 比雌性的多50赫。</td>
			<td>43</td>
		</tr>
<tr>
<td></td>
			<td colspan="4">50赫 USVs 96 只幼年大鼠或52只幼年大鼠的性别差异</td>
			<td>42, 44</td>
		</tr>
<tr>
<td></td>
			<td colspan="4">雌性幼鼠产生的 USVs 比雄性大22赫</td>
			<td>44</td>
		</tr>
<tr>
<td>个体间差异</td>
			<td colspan="4">大鼠发出更多的50赫 USVs 显示减少的方法时间自我管理发痒, 增加的积极判断偏差后发痒, 并增加后海马细胞增殖发痒</td>
			<td>27, 37, 45</td>
		</tr>
<tr>
<td></td>
			<td colspan="4">更多嬉戏的老鼠产生了更多的50赫 USVs</td>
			<td>43</td>
		</tr>
<tr>
<td>应变</td>
			<td colspan="4">没有报告, 但传闻证据表明, 来自不同菌株和育种家的老鼠对发痒的反应不同。当选择高 vs 低50赫 USVs 率时, 大鼠的线分叉。</td>
			<td>22, 26, 42, 46</td>
		</tr>
<tr>
<td>以前的发痒经验</td>
			<td colspan="4">提高50赫超声 USVs 的产量</td>
			<td>12</td>
		</tr>
<tr>
<td>外在</td>
			<td colspan="4"></td>
			<td></td>
		</tr>
<tr>
<td>床上用品</td>
			<td colspan="4">在熟悉的床上用品和没有床上用品的时候, 老鼠产生了更多的50赫 USVs。</td>
			<td>33</td>
		</tr>
<tr>
<td>应力</td>
			<td colspan="4">发痒大鼠1小时, 但不是23小时, 在克制的重音减少了50赫 USVs 生产以后</td>
			<td>47, 48</td>
		</tr>
<tr>
<td>时间</td>
			<td colspan="4">注射前发痒大鼠在增加50赫 USVs 比注射后发痒更有效</td>
			<td>12</td>
		</tr>
<tr>
<td>处理程序的性别</td>
			<td colspan="4">未找到效果</td>
			<td>Panksepp, J. 2014, 未发布的数据</td>
		</tr>
<tr>
<td>处理大鼠的熟悉度</td>
			<td colspan="4">大鼠产生了更多的50赫 USVs 和花更多的时间接近一个熟悉的, 比一个陌生的难题</td>
			<td>11</td>
		</tr>
<tr>
<td>处理程序挠痒的经验/活力的处理程序</td>
			<td colspan="4">影响50赫 USVs 的生产但不偏爱和接近行为</td>
			<td>克卢捷, S. 2011, 未发布的数据</td>
		</tr>
<tr>
<td>针的持续时间 (按处理者/背部触点和针脚之间交替的频率)</td>
			<td colspan="4">更低的小点心 (被解释作为戏剧恳求) 被指挥了到一只手强加 15 s 别针 (克制) 比一只手给发痒以多背接触和别针每十五年代</td>
			<td>11</td>
		</tr>
<tr>
<td>气味 (如香水, 洗发水, 剃须膏) 使用的处理程序</td>
			<td colspan="4">未报告</td>
			<td></td>
		</tr>
<tr>
<td>社会团体规模</td>
			<td colspan="4">在大多数实验中, 个体住房比集体住房增加了对瘙痒的积极反应。在家庭笼子里发痒的群鼠与笼子伴侣减少了这种差异</td>
			<td>7, 22, 27, 36</td>
		</tr>
<tr>
<td>光强</td>
			<td colspan="4">发痒在1000勒克斯减少了50赫 USVs 比25莱克丝。</td>
			<td>43</td>
		</tr>
<tr>
<td>噪声</td>
			<td colspan="4">未报告</td>
			<td></td>
		</tr>
<tr>
<td>在发痒前保持笼子清洁</td>
			<td colspan="4">22赫 USVs 在某些大鼠体内的诱导生产</td>
			<td>12</td>
		</tr>
<tr>
<td>一天中的时间</td>
			<td colspan="4">在光周期开始或结束时, 对50赫 USVs 生产没有影响。光期开始/结束时发痒的大鼠与光或暗周期的中间还没有比较</td>
			<td>克卢捷, S. 2011, 未发布的数据</td>
		</tr>
</tbody></table>表 1: 影响或可能影响大鼠对发痒反应的因素列表, 一种有趣的处理技巧, 意在模仿老鼠的粗暴和翻滚的游戏。

Watch this Scientific Journal Video about Tickling, a Technique for Inducing Positive Affect When Handling Rats at JoVE.com

Tickling, a Technique for Inducing Positive Affect When Handling Rats

本文展示了俏皮处理的规范化应用, 一种用于模拟大鼠粗翻滚游戏的挠性技术。这项技术有效地减少了对人类的可怕反应, 并产生积极的影响时, 大鼠处理共同的畜牧业活动和医疗和研究程序, 如注射。

痒, 一种诱发大鼠正向影响的技术

Handling small animals such as rats can lead to several adverse effects. These include the fear of humans, resistance to handling, increased injury risk ...

tickling-a-technique-for-inducing-positive-affect-when-handling-rats

Research

JoVE Journal

Behavior

38.6K 次观看.  Washington State University. 本文展示了俏皮处理的规范化应用, 一种用于模拟大鼠粗翻滚游戏的挠性技术。这项技术有效地减少了对人类的可怕反应, 并产生积极的影响时, 大鼠处理共同的畜牧业活动和医疗和研究程序, 如注射。

视频: Tickling, a Technique for Inducing Positive Affect When Handling Rats

A Novel Procedure for Evaluating the Reinforcing Properties of Tastants in Laboratory Rats: Operant Intraoral Self-administration

This paper describes a novel method for studying the bio-behavioral basis of addiction to food. This method combines the surgical component of taste reactivity with the behavioral aspects of operant self-administration of drugs. Under very brief general anaesthesia, rats are implanted with an intraoral (IO) cannula that allows delivery of test solutions directly in the oral cavity. Animals are then tested in operant self-administration chambers whereby they can press a lever to receive IO infusions of test solutions. IO self-administration has several advantages over experimental procedures that involve drinking a solution from a spout&#160;or operant responding for solid pellets or solutions delivered in a receptacle. Here, we show that IO self-administration can be employed to study self-administration of high fructose corn syrup (HFCS). Rats were first tested for self-administration on a progressive ratio (PR) schedule, which assesses the maximum amount of operant behavior that will be emitted for different concentrations of HFCS (i.e.&#160;8%, 25%, and 50%). Following this test, rats self-administered these concentrations on a continuous schedule of reinforcement (i.e.&#160;one infusion for each lever press) for 10 consecutive days (1 session/day; each lasting 3 hr), and then they were retested on the PR schedule. On the continuous reinforcement schedule, rats took fewer infusions of higher concentrations, although the lowest concentration of HFCS (8%) maintained more variable self-administration. Furthermore, the PR tests revealed that 8% had lower reinforcing value than 25% and 50%. These results indicate that IO self-administration can be employed to study acquisition and maintenance of responding for sweet solutions. The sensitivity of the operant response to differences in concentration and schedule of reinforcement makes IO self-administration an ideal procedure to investigate the neurobiology of voluntary intake of sweets.

The current study evaluates a novel procedure for assessing the reinforcing effects of palatable solutions in laboratory rats: intraoral self-administration. To this end, operant responding (i.e.&#160;lever pressing) for intraoral infusions of sweet solutions at different concentrations was measured on continuous and progressive ratios schedules of reinforcement.

一种新的方法为评估味质的实验室大鼠的补强性能:操作性口腔自我管理

This paper describes a novel method for studying the bio-behavioral basis of addiction to food. This method combines the surgical component of taste ...

科研

行为学

Fat Preference: A Novel Model of Eating Behavior in Rats

Obesity is a growing problem in the United States of America, with more than a third of the population classified as obese. One factor contributing to this multifactorial disorder is the consumption of a high fat diet, a behavior that has been shown to increase both caloric intake and body fat content. However, the elements regulating preference for high fat food over other foods remain understudied.
To overcome this deficit, a model to quickly and easily test changes in the preference for dietary fat was developed. The Fat Preference model presents rats with a series of choices between foods with differing fat content. Like humans, rats have a natural bias toward consuming high fat food, making the rat model ideal for translational studies. Changes in preference can be ascribed to the effect of either genetic differences or pharmacological interventions. This model allows for the exploration of determinates of fat preference and screening pharmacotherapeutic agents that influence acquisition of obesity.

Dietary fat content influences both energy intake and body fat composition in mammals. By examining rats&#8217; preference for high fat food in a series of choice experiments, it is possible to test genetic differences and pharmacological interventions on their preference for high fat food.

脂肪偏好:饮食行为的一种新模型大鼠

Obesity is a growing problem in the United States of America, with more than a third of the population classified as obese. One factor contributing to ...

A Real-world What-Where-When Memory Test

Episodic memory is a complex memory system which allows recall and mental re-experience of previous episodes from one&#39;s own life. Real-life episodic memories are about events in their spatiotemporal context and are typically visuospatial, rather than verbal. Yet often, tests of episodic memory use verbal material to be recalled (word lists, stories). The Real-World What-Where-When memory test requires participants to hide a total of 16 different objects in 16 different locations over two temporal occasions, 2 h apart. Another two hours later, they are then asked to recall which objects (What) they had hidden in which locations (Where) and on which of the two occasions (When). In addition to counting the number of correctly recalled complete what-where-when combinations, this task can also be used to test real-world spatial memory and object memory. This task is sensitive to normal cognitive aging, and correlates well with performance on other episodic memory tasks, while at the same time providing more ecological validity and being cheap and easy to run.

A Real-world What-Where-When Memory Test

The Real-World What-Where-When memory test is a novel episodic memory test, in which participants need to recall which objects have been hidden in which locations on which of two distinct occasions. It is easy to run and is sensitive to normal cognitive aging.

一个现实世界<em&gt;什么，在哪里，当</em&gt;记忆测试

Episodic memory is a complex memory system which allows recall and mental re-experience of previous episodes from one&#39;s own life. Real-life episodic ...

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 Knob Supination Task: A Semi-automated Method for Assessing Forelimb Function in Rats

Tasks that accurately measure dexterity in animal models are critical to understand hand function. Current rat behavioral tasks that measure dexterity largely use video analysis of reaching or food manipulation. While these tasks are easy to implement and are robust across disease models, they are subjective and laborious for the experimenter. Automating traditional tasks or creating new automated tasks can make the tasks more efficient, objective, and quantitative. Since rats are less dexterous than primates, central nervous system (CNS) injury produces more subtle deficits in dexterity, however, supination is highly affected in rodents and crucial to hand function in primates. Therefore, we designed a semi-automated task that measures forelimb supination in rats. Rats are trained to reach and grasp a knob-shaped manipulandum and turn the manipulandum in supination to receive a reward. Rats can acquire the skill within 20 &plusmn; 5 days. While the early part of training is highly supervised, much of the training is done without direct supervision. The task reliably and reproducibly captures subtle deficits after injury and shows functional recovery that accurately reflects clinical recovery curves. Analysis of data is performed by specialized software through a graphical user interface that is designed to be intuitive. We also give solutions to common problems encountered during training, and show that minor corrections to behavior early in training produce reliable acquisition of supination. Thus, the knob supination task provides efficient and quantitative evaluation of a critical movement for dexterity in rats.

This manuscript describes a semi-automated task that quantifies supination in rats. Rats reach, grasp, and supinate a spherical manipulandum. The rat is rewarded with a pellet if the turn angle exceeds a criterion set by the user. This task increases throughput, sensitivity to injury, and objectivity compared to traditional tasks.

旋钮旋任务: 一种半自动评估大鼠前肢功能的方法

Tasks that accurately measure dexterity in animal models are critical to understand hand function. Current rat behavioral tasks that measure dexterity ...

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

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 no existing format for studying the mechanism of action, prevention, containment, and treatment of contagious depression. The purpose of this study, therefore, was to establish the first animal model of contagious depression.
Healthy rats can contract depressive behaviors if exposed to depressed rats. Depression is induced in rats by subjecting them to several manipulations of chronic unpredictable stress (CUS) over 5 weeks, as described in the protocol. A successful sucrose preference test confirmed the development of depression in the rats. The CUS-exposed rats were then caged with na&#239;ve rats from the contagion group (1 na&#239;ve rat/2 depressed rats in a cage) for an additional 5 weeks. 30 social groups were created from the combination of CUS-exposed rats and na&#239;ve rats.
This proposed depression-contagion protocol in animals consists mainly of cohabiting CUS-exposed and healthy rats for 5 weeks. To ensure that this method works, a series of tests are carried out - first, the sucrose preference test upon inducing depression to rats, then, the sucrose preference test, alongside the open field and forced-swim tests at the end of the cohabitation period. Throughout the experiment, rats are given tags and are always returned to their cages after each test.
A few limitations to this method are the weak differences recorded between the experimental and control groups in the sucrose preference test and the irreversible traumatic outcome of the forced swim test. These may be worth considering for suitability before any future application of the protocol. Nonetheless, following the experiment, na&#239;ve rats developed contagion depression after 5 weeks of sharing the same cage with the CUS-exposed rats.

This protocol describes a new model by which healthy rats could contract depression over a given time periodthrough contagion by exposure to chronic unpredictable stressed (CUS) rats.

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 ...

Testing for Metacognitive Responding Using an Odor-based Delayed Match-to-Sample Test in Rats

Metamemory involves the cognitive ability to assess the strength of one&#39;s memories. To explore the possibility of metamemory in non-human animals, numerous behavioral tasks have been created, many of which utilize an option to decline memory tests. To assess metamemory in rats, we utilized this decline-test option paradigm by adapting previous visual delayed-match-to-sample tests (DMTS)1,2 developed for primate species to an odor-based test suitable for rodents. First,&#160;rats are given a sample to remember by digging in a cup of scented sand. After a delay, the rat is presented with four distinctly scented cups, one of which contains the identical scent experienced during the sample; if this matching cup is selected, then the rat obtains a preferred, larger reward. Selection of any of the other three non-matching sand-filled scented cups results in no reward. Retention intervals are individually titrated such that subjects perform between 40 and 70% correct, therefore ensuring rats sometimes remember and sometimes forget the sample. Here, the operational definition of metamemory is the ability to distinguish between the presence and absence of memory through behavioral responding. Towards this end, on two-thirds of trials, a decline option is presented in addition to the four choice cups (choice trials). If the decline-test option- an unscented colored sand cup, is selected, the subject receives a smaller less-preferred reward and avoids the memory test. On the remaining third of trials, the decline-test option is not available (forced trials), causing subjects to guess the correct cup when the sample is forgotten. On choice tests, subjects that know when they remember should select the decline option when memory is weak rather than take the test and choose incorrectly. Therefore, significantly higher performance on chosen tests as compared to forced memory tests is indicative of the adaptive use of the decline-test response and metacognitive responding.

This protocol describes a method for investigating the possibility of metamemory, or memory awareness, in rodents. The odor-based delayed-matching-to-sample paradigm is a novel, ecologically-relevant behavioral test useful for determining the extent to which rodents can adaptively respond based on cognitively monitoring the strength of their memory states.

用基于气味的延迟配对试验对大鼠元认知应答的测试

Metamemory involves the cognitive ability to assess the strength of one&#39;s memories. To explore the possibility of metamemory in non-human animals, ...

A Conditioned Place Preference Protocol for Measuring Incubation of Craving in Rats

A major cause of repeated relapses is a craving for the drug. Drug craving increases progressively during the abstinence period, a phenomenon termed incubation of drug craving. Here, we describe a morphine conditioned place preference (CPP) protocol for measuring the incubation of craving in rats. In this protocol, a CPP paradigm mainly employing somatosensory cues is used to establish a long-term reward memory of morphine. A three-chamber CPP box that differs in the texture of the chamber floor is constructed. First, the animals are tested for their baseline preference to the two side chambers for three consecutive days. Then, they are injected intraperitoneally with morphine/saline and put into their non-preferred/preferred chamber for 45 min. After 6 days of conditioning, their preference to the side chambers is tested for 15 min at different time points after the last conditioning session. With this paradigm, the reward memory of morphine could last for at least 18 days. To test whether the above-mentioned protocol can model increased craving, the number of entrances into the two side chambers are counted during the abstinence period. The results show that the entrances increased, suggesting that the CPP paradigm could mimic the incubation of craving. Future studies can employ this model to study neural mechanisms underlying long-term memory and incubation of craving.

Here, a morphine conditioned place preference (CPP) protocol is described to measure incubation of craving in rats.

一种用于大鼠渴望培养的条件场所偏好协议

A major cause of repeated relapses is a craving for the drug. Drug craving increases progressively during the abstinence period, a phenomenon termed ...

A Middle Cerebral Artery Occlusion Technique for Inducing Post-stroke Depression in Rats

Post-stroke depression (PSD) is the most recurrent of all psychiatric complications resulting from an ischemic stroke. A greater majority (about 60%) of all ischemic stroke patients suffer from PSD, a disorder considered to be an ischemic stroke-related precursor for increased death and degradation in health. The pathophysiology of PSD is still obscure. To study the mechanism of development and occurrence of PSD further, and to find out a therapy, we attempted to develop a new protocol that requires occluding the middle cerebral artery (MCA) via the internal carotid artery (ICA) in rats. This protocol describes a model of PSD induced in rats through the middle cerebral artery occlusion (MCAO). Also used in the experiment are the Porsolt forced swim test and the sucrose preference test to confirm and evaluate the depressive mood of the rats under investigation. Rather than inserting the catheter through the external carotid artery (ECA), as stipulated for the original procedure, this MCAO technique has the monofilament passing directly through the ICA. This MCAO technique was developed a few years ago and leads to a reduction in mortality and variability. It is generally accepted that the criteria used are preferred in the selection of biological models. The data obtained with this protocol show that this model of MCAO could be a way of inducing PSD in rats and could potentially lead to the understanding of the pathophysiology and the future development of new drugs and other neuroprotective agents.

Here we present a protocol to induce post-stroke depression in rats by occluding the middle cerebral artery via the internal carotid artery. We use the Porsolt forced swim test and the sucrose preference test to confirm and evaluate induced depressive moods.

一种中脑动脉闭塞技术在大鼠脑卒中后抑郁中的诱导

Post-stroke depression (PSD) is the most recurrent of all psychiatric complications resulting from an ischemic stroke. A greater majority (about 60%) of ...

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, ...