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, 以此为主要手段的诱发抑郁症的动物。结果表明, 该方法与临床症状和抑郁症状行为有很强的相似性。如果在大鼠身上使用得当, 大鼠 canexpress 所有已知的抑郁症状26。在大鼠身上应用所有抑郁行为的能力验证了作为一种可靠的抑郁诱导方法, 具有较高的可预见性和构造有效性27, 28。该方法同样被用作动物抑郁症模型来分析抑郁症的病理生理学的细胞和分子机制, 并研究抗抑郁药的作用机制29,30,31,32,33。
在抑郁和天真大鼠同居后应用蔗糖偏好试验, 对抑郁症的传播进行了评价, 导致两组大鼠在5周后抑郁行为的表达 (图 2,图 3,图 4)。强制游泳测试20和开放字段测试34,35,36, 37,38,39,40也被用来调查大鼠抑郁症41。这些方法反映了广泛的行为不规则。没有具体的传染机制的事实意味着有意识的和无意识的组成部分可以作为潜在的假设结果被推进。无意识可以通过模仿42表现出来, 通过健康的老鼠复制抑郁大鼠的身体运动。最有可能被复制的运动如面部表情和神经元系统43。另一方面, 意识可以通过沟通方式产生。一个这样的方法是共同沉思44。
虽然健康的老鼠在与抑郁的大鼠分享住房时变得沮丧, 但与他们的健康伴侣同居后, 抑郁的老鼠与他们的状态相比也变得不那么抑郁了。这是在较早前的研究结果中观察到的, 当抑郁的大学生在与他们的健康室友共度一段时间后, 能够打哈欠成为 undepressed4。因此, 不仅有传染性抑郁症的负面影响, 而且还有相互作用。抑郁的个体对健康的人有消极的影响, 而他们自己却因接触到不抑郁的同事而稍稍从抑郁症中恢复过来。这样的发现可能会促进精神病学在处理抑郁症的个人和人口。
在这个测试之前, 动物模型的抑郁症-传染是不存在的, 即使在这里取得了突破, 这个测试有它的局限性。由于一些原因, 它可以被认为有些薄弱。与受控大鼠相比, 被认为抑郁的老鼠的蔗糖摄取量和吸水率的差异并不显著, 也不是实验大鼠高度抑郁状态的指示。此外, 如果能找到更好的替代方案, 使用强制游泳测试也不可取。这项试验造成的损害是创伤性的、永久性的和不可逆转的。因此, 受强迫游泳试验的动物不能被回收或用于进一步的实验。无论方法的缺点是什么, 它仍然是一个开创性的方法, 产生了体面的结果。
人们已经说和做了很多事情来应对抑郁症, 但它仍然是令人担忧的一个主要原因, 随着威胁生命的情况日益增多, 当今社会的严重性凸显出来。复杂的性质定义人类之间的相互作用, 使它有问题的系统性评估抑郁症传染。因此, 对动物模型的深入了解可能是解开人类抑郁症发病机制的关键, 随后为这一疑难病症建立治疗答案。

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 border="0" cellpadding="0" cellspacing="0" style="width:849px;" width="849">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="40">
			<td height="40" style="height:40px;width:216px;">Rat Cages</td>
			<td style="width:123px;">Techniplast</td>
			<td style="width:344px;">2000P</td>
			<td style="width:167px;">Conventional housing for rodents. Was used for housing rats throughout the experiment</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Water</td>
			<td>-</td>
			<td>-</td>
			<td style="width:167px;">Common tap water used througout the experiment at different stages</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Purina Chow</td>
			<td>Purina</td>
			<td>5001</td>
			<td style="width:167px;">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 height="40">
			<td height="40" style="height:40px;">Bottles</td>
			<td>Techniplast</td>
			<td>ACBT0262SU</td>
			<td style="width:167px;">150 ml bottles filled with 100 ml of water and 100 ml 1%(w/v) sucrose solution</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Black lusterless perspex box</td>
			<td>-</td>
			<td>-</td>
			<td style="width:167px;">(120 cm &#215; 60 cm &#215; 60 cm), divided into a 25% central zone and the surrounding border zone</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Video Camera</td>
			<td>Canon</td>
			<td>-</td>
			<td style="width:167px;">Digital video camera for high definition recording of rat behavior under open field test</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Alcohol</td>
			<td>Pharmacy</td>
			<td>-</td>
			<td style="width:167px;">99% pharmaceutical alcohol diluted to 5% and used for lceaning the open field test box before the introduction of each rat</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Glass cylinder</td>
			<td>-</td>
			<td>-</td>
			<td style="width:167px;">100 cm tall, 40 cm in diameter, and 40 cm deep cylinder used for carrying out the forced swim test</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Paper towels</td>
			<td>Pharmacy</td>
			<td>-</td>
			<td style="width:167px;">Dry towels used for keeping rats dry after immersing them in water</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Bold markers</td>
			<td>-</td>
			<td>-</td>
			<td style="width:167px;">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 @ 95,图 3.4%) 相比, 60 的大鼠表现出统计学上的显著变化 (72 3.3%, p < 0.001,图 2), 30 的抑郁症-传染大鼠 (76 @ 4.7% p< 0.001,图 2), 5 周后, 与该暴露的老鼠同居。
打开的字段测试:由于暴露的和抑郁传染的人群中的大鼠总旅行距离减少 (抑郁症传染-p < 0.05 和为暴露-p < 0.01,图 3A) 和减少平均速度 (由于暴露 p < 0.05, 图 3C), 与控件组比较。从对照组和两个实验组的开放 fieldby 鼠的中心所花的时间不显著不同 (图 3B)。
强制游泳测试:不动的评价结果如预期。在强迫游泳试验后, 由于暴露的和抑郁症状的大鼠都表现出了延长的静止状态。但是, 在与对照组 (图 4a) 进行比较时, 仅在受影响的老鼠 (p < 0.01) 中注册了明显延长的不活动时间。在另一项被调查的强迫游泳测试参数, 攀登时间, 两组的暴露和传染抑郁症大鼠表现出高度有限的攀登属性 (p < 0.01) 相比, 对照组 (图 4B)。与控制 (图 4C) 相比, 对排便率的评估导致了两个实验组 (p < 0.01) 的大量粪便的登记。
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/57137/57137fig1.jpg"> 图 1: 实验性协议设计。显示各自实验协议的顺序和时间。<a href="//cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/57137/57137fig1large.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/57137/57137fig2.jpg"> 图 2: 蔗糖首选项测试.60只因暴露的大鼠 (65 @ 2.8% vs 101 @ 7%, p < 0.001) 与对照组30个大鼠相比, 其蔗糖偏爱试验的百分比变化显著降低。60的蔗糖偏好测试中有显著的百分比变化 (72 3.3%, p < 0.001) 和30抑郁症-传染 (76 在 4.7%, p < 0.001) 鼠在10星期以后, 与控制组30个老鼠相比 (95 @ 3.4%)。对 Bonferroni 的自组后测试进行了单向方差分析。数据显示为基线的百分比, 并表示为平均值 "电子扫描电镜<a href="//cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/57137/57137fig2large.jpg" target="_blank">". 请单击此处查看此图的较大版本.</a>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/57137/57137fig3.jpg"> 图 3: 打开的字段测试.两个抑郁症-传染 (68.1) 6.5%, p < 0.05,图 3A) 和因暴露的老鼠 (59.6 @ 5.7%, p < 0.01,图 3A) 减少了总旅行距离, 与控制鼠相比 (100 @ 13%,图 3A). 在打开字段的中心部分 (图 3B) 中的所有3组老鼠所花费的时间上没有发现显著差异。被暴露的 (75.4 @ 6%, p < 0.05,图 3C) 和郁闷传染 (88 @ 5.6%, p < 0.005,图 3C) 大鼠两者均降低了平均速度, 但仅记录了显著变化组, 与对照组大鼠比较。在所有3项测试中, 克鲁斯卡尔-沃利斯, 其次是曼-惠特尼测试被使用。数据以控制组的百分比形式显示, 并以 "平均值" (SEM) 表示.<a href="//cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/57137/57137fig3large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/57137/57137fig4.jpg"> 图 4: 强制游泳测试.被暴露的 (151 @ 3.3%, p < 0.01,图 4A) 和抑郁症传染 (107 @ 6.7%,图 4A) 老鼠都被发现是高度不动的, 但一个重大的变化只记录在其暴露的组, 比对照组的大鼠。由于暴露 (46 @ 5.5%, p < 0.01,图 4B) 和抑郁症传染 (64 @ 5.4% p < 0.01,图 4B) 老鼠都表示减少攀登时间。与4控制的排便率相比, 60 例大鼠的排便率 (278 @ 32%, p < 0.01,图 30C) 和131抑郁症-传染大鼠 (37% @ 4,图 30C) 显著大于大鼠 (100 22.5%, p < 0.01)。自检后分析发现抑郁症传染大鼠与对照组之间没有显著差异, 但与对照鼠相比 (p < 0.01图 4C) 显示出显著差异。采用单因素方差分析方法进行统计学研究。数据显示为 groupand 表示为平均值的控件的百分比.<a href="//cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/57137/57137fig4large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>

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

Nanyang Technological University

Research

JoVE Journal

Behavior

20.7K 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

A Procedure to Study the Effect of Prolonged Food Restriction on Heroin Seeking in Abstinent Rats

In human drug addicts, exposure to drug-associated cues or environments that were previously associated with drug taking can trigger relapse during abstinence. Moreover, various environmental challenges can exacerbate this effect, as well as increase ongoing drug intake.
The procedure we describe here highlights the impact of a common environmental challenge, food restriction, on drug craving that is expressed as an augmentation of drug seeking in abstinent rats.
Rats are implanted with chronic intravenous i.v. catheters, and then trained to press a lever for i.v. heroin over a period of 10-12 days. Following the heroin self-administration phase the rats are removed from the operant conditioning chambers and housed in the animal care facility for a period of at least 14 days. While one group is maintained under unrestricted access to food (sated group), a second group (FDR group) is exposed to a mild food restriction regimen that results in their body weights maintained at 90% of their nonrestricted body weight. On day 14 of food restriction the rats are transferred back to the drug-training environment, and a drug-seeking test is run under extinction conditions (i.e.&#160;lever presses do not result in heroin delivery).
The procedure presented here results in a highly robust augmentation of heroin seeking on test day in the food restricted rats. In addition, compared to the acute food deprivation manipulations we have used before, the current procedure is a more clinically relevant model for the impact of caloric restriction on drug seeking. Moreover, it might be closer to the human condition as the rats are not required to go through an extinction-training phase before the drug-seeking test, which is an integral component of the popular reinstatement procedure.

A procedure that allows a demonstration of robust augmentation of drug seeking in food-restricted rats is described. Following heroin self-administration training, rats go through an abstinence period, in a drug-free environment, during which they are mildly food restricted. Drug seeking is then tested in the drug-associated environment.

一个过程来研究延长食品的限制对海洛因寻求戒断大鼠的影响

In human drug addicts, exposure to drug-associated cues or environments that were previously associated with drug taking can trigger relapse during ...

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 Procedure to Observe Context-induced Renewal of Pavlovian-conditioned Alcohol-seeking Behavior in Rats

Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate drug-seeking behavior and prompt relapse in abstinent drug users. We have developed a procedure to study the behavioral and neural processes that mediate the impact of context on alcohol-seeking behavior in rats. Following acclimation to the taste and pharmacological effects of 15% ethanol in the home cage, male Long-Evans rats receive Pavlovian discrimination training (PDT) in conditioning chambers. In each daily (Mon-Fri) PDT session, 16 trials each of two different 10 sec auditory conditioned stimuli occur. During one stimulus, the CS+, 0.2 ml of 15% ethanol is delivered into a fluid port for oral consumption. The second stimulus, the CS-, is not paired with ethanol. Across sessions, entries into the fluid port during the CS+ increase, whereas entries during the CS- stabilize at a lower level, indicating that a predictive association between the CS+ and ethanol is acquired. During PDT each chamber is equipped with a specific configuration of visual, olfactory and tactile contextual stimuli. Following PDT, extinction training is conducted in the same chamber that is now equipped with a different configuration of contextual stimuli. The CS+ and CS- are presented as before, but ethanol is withheld, which causes a gradual decline in port entries during the CS+. At test, rats are placed back into the PDT context and presented with the CS+ and CS- as before, but without ethanol. This manipulation triggers a robust and selective increase in the number of port entries made during the alcohol predictive CS+, with no change in responding during the CS-. This effect, referred to as context-induced renewal, illustrates the powerful capacity of contexts associated with alcohol consumption to stimulate alcohol-seeking behavior in response to Pavlovian alcohol cues.

A procedure to study the capacity of an alcohol associated environmental context to trigger the renewal of alcohol-seeking behavior in rats is described.

一个过程来观察大鼠巴甫洛夫空调酒精寻求行为的背景下引发的重建

Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate ...

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 Modified Hole Board - Measuring Behavior, Cognition and Social Interaction in Mice and Rats

This protocol describes the modified hole board (mHB), which combines features from a traditional hole board and open field and is designed to measure multiple dimensions of unconditioned behavior in small laboratory mammals (e.g., mice, rats, tree shrews and small primates). This paradigm is a valuable alternative for the use of a behavioral test battery, since a broad behavioral spectrum of an animal&#8217;s behavioral profile can be investigated in one single test.
The apparatus consists of a box, representing the &#8216;protected&#8217; area, separated from a group compartment. A board, on which small cylinders are staggered in three lines, is placed in the center of the box, representing the &#8216;unprotected&#8217; area of the set-up. The cognitive abilities of the animals can be measured by baiting some cylinders on the board and measuring the working and reference memory. Other unconditioned behavior, such as activity-related-, anxiety-related- and social behavior, can be observed using this paradigm. Behavioral flexibility and the ability to habituate to a novel environment can additionally be observed by subjecting the animals to multiple trials in the mHB, revealing insight into the animals&#8217; adaptive capacities.
Due to testing order effects in a behavioral test battery, na&#239;ve animals should be used for each individual experiment. By testing multiple behavioral dimensions in a single paradigm and thereby circumventing this issue, the number of experimental animals used is reduced. Furthermore, by avoiding social isolation during testing and without the need to food deprive the animals, the mHB represents a behavioral test system, inducing if any, very low amount of stress.

This protocol describes the modified hole board, which is a behavioral test set-up that comprises the characteristics of an open field and a traditional hole board. This set-up enables the differential analysis of unconditioned behavior of small laboratory mammals as well as the analysis of cognitive abilities.

修改后的孔板 - 测量行为，认知和社会互动小鼠和大鼠

This protocol describes the modified hole board (mHB), which combines features from a traditional hole board and open field and is designed to measure ...

The Rodent Psychomotor Vigilance Test (rPVT): A Method for Assessing Neurobehavioral Performance in Rats and Mice

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article describes a rodent version of the PVT&#8212;termed the &#34;rPVT&#34;&#8212;that measures similar aspects of attention (i.e., performance accuracy, motor speed, premature responding, and lapses in attention). Data are presented that demonstrate both the short- and long-term usefulness of the rPVT when employed with laboratory rats. Rats easily learn the rPVT, and learning to perform the basic procedure takes less than two weeks of training. Once acquired, rat performances in the rPVT show a high degree of similarity to these same performance measures in the human PVT, including similarities in, lapses in attention, reaction times, vigilance decrements across session time (i.e., the human &#34;time-on-task&#34; effects), and the response-stimulus interval (RSI) effect described for humans. Thus the rPVT can be an extremely valuable tool for assessing the effects of a wide range of variables on sustained attention quite similar to human PVT performances, and thus can be useful for developing novel treatments for neurobehavioral dysfunctions.

The Rodent Psychomotor Vigilance Test rPVT: A Method for Assessing Neurobehavioral Performance in Rats and Mice

A rat version of the human Psychomotor Vigilance Test (PVT) is described that measures aspects of attention similar to those measured with the human PVT, including aspects of human vigilance such as performance accuracy, motor speed, premature responding, and lapses in attention.

鼠类精神运动警觉测试（rPVT）:一个在大鼠和小鼠的神经行为评估性能的方法

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article ...

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 ...

Tickling, a Technique for Inducing Positive Affect When Handling Rats

Handling small animals such as rats can lead to several adverse effects. These include the fear of humans, resistance to handling, increased injury risk for both the animals and the hands of their handlers, decreased animal welfare, and less valid research data. To minimize negative effects on experimental results and human-animal relationships, research animals are often habituated to being handled. However, the methods of habituation are highly variable and often of limited effectiveness. More potently, it is possible for humans to mimic aspects of the animals&#39; playful rough-and-tumble behavior during handling. When applied to laboratory rats in a systematic manner, this playful handling, referred to as tickling, consistently gives rise to positive behavioral responses. This article provides a detailed description of a standardized rat tickling technique. This method can contribute to future investigations into positive affective states in animals, make it easier to handle rats for common husbandry activities such as cage changing or medical/research procedures such as injection, and be implemented as a source of social enrichment. It is concluded that this method can be used to efficiently and practicably reduce rats&#39; fearfulness of humans and improve their welfare, as well as reliably model positive affective states.

This article demonstrates the standardized application of playful handling, a tickling technique designed to mimic rat rough-and-tumble play. This technique is effective at reducing fearful reactions to humans and generating positive affect when rats are handled for common husbandry activities and medical and research procedures such as injection.

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 ...

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, ...