This work was funded by the University of Michigan Department Of Psychiatry (U032826; JDM), the National Institute on Drug Abuse (NIDA; K08 DA037912-01; JDM) and the Department of Defense (DoD) National Defense Science and Engineering Graduate (NDSEG) Fellowship (CJF).

所有的程序已通过大学委员会关于动物的使用和保养（UCUCA，密歇根大学安娜堡分校，MI）。 1.设备和软件<ol><li>获得商业操作室和设备。见材料表 。 </li><li>在大鼠操作性条件反射室进行培训（24.1厘米宽×20.5厘米深x29.2厘米高度），坐落在声音衰减柜通风爱好者提供环境噪音。 </li><li>装备有颗粒杂志（插座）各室，位于中央的操作性室的不锈钢格地板3厘米以上的21.6厘米宽的前壁。确保粒料杂志包含的红外线传感器，其能够检测头项到器件中。 </li><li>沉淀杂志连接到颗粒机，它提供了香蕉味的食物颗粒（45毫克）。 </li><li>在反平衡的方式，位置的一个可伸缩乐版本（CS）的粒料插座的任一侧约2.5厘米的不锈钢网格地板3厘米以上（左或右）。 </li><li>确保杠杆包含在其中一个LED提示灯，使延长杆更直观醒目。 </li><li>如果使用的是可伸缩的杆，通过由本身放置每分钟10校正重块上的杆的顶端，然后调整校准螺钉（位于设备的顶部）用六角螺母扳手直至重量校准杆是能够抑制杠杆。 </li><li>在室的上盒容器相对的壁的顶部装备一个红房子光。 注:红房子光用来增加照明杆的显眼。 </li></ol> 2. PCA培训<ol><li>对内部成年雄性SD大鼠（250-300 G）抵达后，让他们不受干扰的住房群体，这是维持12小时的光/暗周期至少两天。 </li><li>轻轻地处理EACH鼠为以适应大鼠与人接触，每天至少1分钟两天。提供在外壳菌落食物和水的大鼠随意存取。 </li><li>通过放置在他们的家笼的食物颗粒（每鼠约15丸）两天，前三天PCA训练开始熟悉香蕉味的食物颗粒只。 注意:如果老鼠是成对安置，它对家笼的两侧均匀地划分粒料是有用的。 </li><li>训练前计划 注意:使用MEDState符号（医学协会，软件）执行我们所有的编程，而手册可在网上​​（mednr.com/pdf/doc003_MedPCProgramr.pdf）。程序编写为使用MedState符号无格式文本文件 （例如，ASCII或DOS文本），保存与适当延长（即，[文件名​​] .mpc），然后使用MED-PC程序，跨IV翻译。所有的这些步骤中提供了更详细地在上述亲编程手册。 <ol><li>创建一个训练前程序，该程序（即，一种食物小球，平均每30秒传送开始后5分钟，提供一个可变时间50的食物颗粒（VT）30秒的时间表，但实际交付0-之间随机变化60秒）。 </li><li>写训练前的程序使得红房子亮，但仍杆缩回的（约25分钟）计划的持续时间。 </li><li>光周期中进行训练前和所有后续实验。 </li><li>一天前PCA训练，每只大鼠放入一个操作性室，关闭并锁上房门，并关闭声音衰减柜门。 </li><li>将每只大鼠在其室后尽快启动训练前程序。 </li><li>从它的腔尽快程序结束后取出每只大鼠。 </li><li>记录消耗颗粒的数目和排除大鼠不消耗所有的进一步的测试颗粒。 </li></ol></li><li>创建提供了约40分钟，25项试验，该程序开始后开始1分钟PCA培训计划。 <ol><li>编写程序，使每个审判期间杆延伸到室和照明，持续8秒。 </li><li>程序杆回缩到通过一种食物丸的响应无关输送到粒料杂志立即执行。 </li><li>独立于VT 90秒的时间安排每个试验（ 即杠杆扩展和随后的食物颗粒交货时平均每90秒，但实际交付30-150秒之间随机变化）。 </li><li>每只大鼠放入调理室，关闭并锁上房门，并关闭声音衰减柜门。 </li><li>将每只大鼠在其室后尽快启动PCA培训计划。 </li><li>从它的腔尽快程序结束后取出每只大鼠。 </li><li> Ëxclude大鼠不消耗所有的颗粒从进一步测试。 </li></ol></li></ol> 3.数据处理<ol><li>转移输出信息到电子表格（例如，电子表格文档）。 </li><li>创建提取物识别信息的信息（受试者编号，开始日期，开始时间，和框数）以及输出信息（号码和杠杆压力机和杂志条目延迟）。 注:在实验中，非CS杂志条目也由轮廓提取。定义非CS杂志条目作为8秒CS周期的外侧和VT 90秒（ 即 ，60-120秒）的期间，该杆并不延伸过程中发生的项到杂志。 </li><li>通过在8秒封盖杠杆新闻和杂志进入潜伏期进一步处理数据（即CS呈现的持续时间）。这可以在电子表格中通过IF函数来实现:IF（X&gt; 8,8，X）。 </li><li>分数计算为响应偏差 （即杠杆压力机和杂志条目会话总数;杠杆压力机-杂志条目] / [杠杆压力机+杂志条目]），潜伏期评分（ 即平均延迟执行的杠杆压或杂志进入在会话过程中;杂志进入潜伏期-杆按延迟] / 8），和概率差（ 即杠杆压力机或杂志条目的比例;杠杆压概率-杂志入门概率]）5。 注意:使用这些公式，所有得分应1.0和-1.0之间。 </li><li>每个单独的会话内的平均反应偏差，延迟得分和概率差异计算PCA指数得分为每个老鼠。 注:PCA指数得分应该1.0和-1.0之间。 </li></ol>

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The authors have nothing to disclose.

PCA训练可被用来确定在该倾向的个体差异来激励突性归因于空调线索，这已被认为是成瘾漏洞的一个重要组成部分。例如，以前已经证明，ST的属性激励突性到食品和药物线索6，和两个食品和药物相关的线索中的ST 7的杏仁核-纹状体-丘脑回路内激活相似的大脑区域。此外，ST的都比较浮躁8，易受毒品寻求行为线索7,9诱发复职，并寻求与药物有关的线索，尽管不良?...

使用药物上瘾的过渡涉及巴甫洛夫和器乐学习1,2之间复杂的相互作用。在吸毒和毒品寻求行为，行动和成果是通过仪器过程的经验教训;然而，刺激（ 如药物相关线索）和回报之间的关系也通过巴甫洛夫过程的经验教训。巴甫洛夫线索获得预测值，但也能获得奖励的激励值 3，因此他们成为有吸引力的，可取的，能够促进和维持奖励寻求行为4。 很多程序调查的奖励动物学习，但是，不允许的预测与激励激励学习解开。在药物的自我管理程序，例如，既有器乐和巴甫洛夫突发通常采用，例如，老鼠学会执行操作（ 例如 ，鼻百吉NG，杠杆压，以便接收的结果（即，静脉输注药物）等）。该奖励成果还配备了巴甫洛夫刺激（ 例如，一个鼻子戳口，提示灯介绍，输液泵的声音，流体输送到血液中感受性的感觉， 等照明）。正是在这些过程往往不清楚线索是否支持目标导向行动仅仅是因为他们与奖励预测的关系，或暗示是否获得自己的奖励激励属性。 为了实验隔离巴甫洛夫刺激的预测值奖励激励价值，我们的实验室使用了巴甫洛夫条件方法（PCA）程序，以确定该属性突出激励来奖励有关的线索老鼠。在训练过程中，条件刺激（CS;例如，杠杆）响应独立预测的deliv（;例如，一个食物颗粒美国）的非条件刺激的红霉素。在多个培训课程的过程中，三表型发展:登录跟踪（CS定向条件反应[CR]），目标跟踪（US-执导CR），以及中间的反应（包括CRS）。对于目标跟踪（GTS），在CS被用作奖励交付的预测;然而，登录追踪器（STS），该CS是由于与激励突出，成为有吸引力的和可取的。在这次审查中，我们勾勒出设备，设置和数据的必要的处理来执行PCA过程。此外，我们提供培训PCA代表性的成果，勾勒出重要的实验方面的考虑，并讨论在调查成瘾等神经精神障碍的PCA程序假定的效用。

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	<tbody>
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			<td>Standard Modular Operant Test Chamber with Modified Top for Rat</td>
			<td>Med Associates, Inc.</td>
			<td>ENV-008CT</td>
			<td>Top has access slot for drug delivery leashes or other harness systems; comes with ENV-008CTC (Cover Insert) for access slot</td>
		</tr>
		<tr>
			<td>Expanded PVC Sound Attenuating Cubicle</td>
			<td>Med Associates, Inc.</td>
			<td>ENV-022V</td>
			<td></td>
		</tr>
		<tr>
			<td>PCI Operating Package for up to Sixteen Chambers</td>
			<td>Med Associates, Inc.</td>
			<td>MED-SYST-16</td>
			<td>Based on the number of operant chambers, MED-SYST-8 (PCI Operating Package for up to Eight Chambers) is also available</td>
		</tr>
		<tr>
			<td>SmartCtrl</td>
			<td>Med Associates, Inc.</td>
			<td>DIG-716P2</td>
			<td></td>
		</tr>
		<tr>
			<td>Universal Cable, 25&#8242; (7.6 m)</td>
			<td>Med Associates, Inc.</td>
			<td>SG-210CB</td>
			<td>Based on individual needs, SG-210CB-50 (Universal Cable, 50&#8242; [15.2 m]) is also available</td>
		</tr>
		<tr>
			<td>18&#8243; (45.7 cm) 3-Pin Mini-Molex</td>
			<td>Med Associates, Inc.</td>
			<td>SG-216A</td>
			<td>Based on individual needs, SG-216A-2 (2&#8242; [61.0 cm] 3-Pin Mini-Molex) is also available</td>
		</tr>
		<tr>
			<td>Power Cable, 25&#8242; (7.6 m)&#160;</td>
			<td>Med Associates, Inc.</td>
			<td>SG-210CP-25</td>
			<td></td>
		</tr>
		<tr>
			<td>Stainless Steel Grid Floor for Rat</td>
			<td>Med Associates, Inc.</td>
			<td>ENV-005</td>
			<td>Based on preference, ENV-005A (Stainless Steel Grid Floor for Mouse) is also available&#160;</td>
		</tr>
		<tr>
			<td>Reusable Waste Pan</td>
			<td>Med Associates, Inc.</td>
			<td>ENV-007-P3</td>
			<td></td>
		</tr>
		<tr>
			<td>Filler Panel Package for Standard Modular Test Chamber</td>
			<td>Med Associates, Inc.</td>
			<td>ENV-008-FP</td>
			<td></td>
		</tr>
		<tr>
			<td>Modular Pellet Dispenser for Rat, 45mg</td>
			<td>Med Associates, Inc.</td>
			<td>ENV-203M-45</td>
			<td></td>
		</tr>
		<tr>
			<td>Pellet Receptacle, Trough Type</td>
			<td>Med Associates, Inc.</td>
			<td>ENV-200R2M</td>
			<td>Based on preference, ENV-200R1M (Pellet Receptable, Cup Type) is also available&#160;</td>
		</tr>
		<tr>
			<td>Retractable Lever</td>
			<td>Med Associates, Inc.</td>
			<td>ENV-112CM</td>
			<td>Calibrated to 25 g; needs to be adjusted to 10 g before Pavlovian conditioned approach training</td>
		</tr>
		<tr>
			<td>Retractable Lever Cue Light</td>
			<td>Med Associates, Inc.</td>
			<td>ENV-112CML</td>
			<td></td>
		</tr>
		<tr>
			<td>House Light for Rat</td>
			<td>Med Associates, Inc.</td>
			<td>ENV-215M</td>
			<td></td>
		</tr>
		<tr>
			<td>100 mA Replacement Bulbs, Pack of 10</td>
			<td>Med Associates, Inc.</td>
			<td>SG-800R</td>
			<td>Red-colored; for use with ENV-215M (House Light for Rat)</td>
		</tr>
		<tr>
			<td>Pellets, 45 mg, Primate Purified Diet, Banana Flavor</td>
			<td>Bio-Serv</td>
			<td>F0059</td>
			<td>50,000/box&#160;</td>
		</tr>
	</tbody>
</table>

pavlovian conditioned approach training in rats

那些偶然与无条件的，有益的刺激配对可以通过称为奖励突出的归属，或中性刺激转变为诱人的过程获得奖励属性本身的线索，"通缉令"能够激励行为的刺激。巴甫洛夫条件方法（PCA）一个条件刺激的响应无关的介绍后发展;即预测的非条件刺激的递送（CS 例如 ，杠杆）（美国;例如，一个食物丸），并且可以被用于测量激励突出在训练期间，三个图案。的空调的响应（CRS）可以发展:登录跟踪行为（CS-定向CR），目标跟踪行为（美国定向CR）和一个中间响应（两者CRS）登录跟踪属性激励突出奖励相关线索和更容易受到毒品寻求线索诱发复职以及其他成瘾相关的行为，使PCA锅为研究成瘾漏洞entially有价值的过程。这里，我们描述用于从大鼠引起的PCA行为以及分析和解释在个别实验的PCA行为的材料和方法。

我们已发现，5-7 PCA训练的日常会话足以表现型大鼠作为STS，燃气轮机和中间反应数（IRs），虽然大鼠还可以基于特定的实验室或实验的需要进行培训。表型是基于PCA指标分数，这是通过如先前在协议中所述的平均的响应偏差，延迟的分数，以及个别会话概率差计算。表型是由从最后两个PCA培训班的平均PCA指数得分确定（ 即会话4和5，如果有一共有五个PCA培训课）。...

Watch this Scientific Journal Video about Pavlovian Conditioned Approach Training in Rats at JoVE.com

Pavlovian Conditioned Approach Training in Rats

Here, we present a protocol to elicit Pavlovian conditioned approach behavior in rats. This procedure can be used to measure individual differences in the tendency to approach and attribute incentive salience to reward-related cues and investigate addiction vulnerability.

大鼠条件性巴甫洛夫训练方法

Cues that are contingently paired with unconditioned, rewarding stimuli can acquire rewarding properties themselves through a process known as the ...

pavlovian-conditioned-approach-training-in-rats

Universidad de Cartagena UDEC

Research

JoVE Journal

Behavior

10.9K 次观看.  University of Michigan. Here, we present a protocol to elicit Pavlovian conditioned approach behavior in rats. This procedure can be used to measure individual differences in the tendency to approach and attribute incentive salience to reward-related cues and investigate addiction vulnerability. 

视频: Pavlovian Conditioned Approach Training in Rats

Stereotaxic Microinjection of Viral Vectors Expressing Cre Recombinase to Study the Role of Target Genes in Cocaine Conditioned Place Preference

Microinjecting recombinant adenoassociated viral (rAAV) vectors expressing Cre recombinase into distinct mouse brain regions to selectively knockout genes of interest allows for enhanced temporally- and regionally-specific control of gene deletion, compared to existing methods. While conditional deletion can also be achieved by mating mice that express Cre recombinase under the control of specific gene promoters with mice carrying a floxed gene, stereotaxic microinjection allows for targeting of discrete brain areas at experimenter-determined time points of interest. In the context of cocaine conditioned place preference, and other cocaine behavioral paradigms such as self-administration or psychomotor sensitization that can involve withdrawal, extinction and/or reinstatement phases, this technique is particularly useful in exploring the unique contribution of target genes to these distinct phases of behavioral models of cocaine-induced plasticity. Specifically, this technique allows for selective ablation of target genes during discrete phases of a behavior to test their contribution to the behavior across time. Ultimately, this understanding allows for more targeted therapeutics that are best able to address the most potent risk factors that present themselves during each phase of addictive behavior.

This article describes how to microinject viral vectors into mouse brain and then test in a conditioned place preference paradigm that includes an acquisition, extinction and reinstatement phase.

立体定向显微注射病毒载体表达Cre重组酶研究的靶基因的作用在可卡因条件性位置偏爱

Microinjecting recombinant adenoassociated viral (rAAV) vectors expressing Cre recombinase into distinct mouse brain regions to selectively knockout genes ...

科研

行为学

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 ...

Training Synesthetic Letter-color Associations by Reading in Color

Synesthesia is a rare condition in which a stimulus from one modality automatically and consistently triggers unusual sensations in the same and/or other modalities. A relatively common and well-studied type is grapheme-color synesthesia, defined as the consistent experience of color when viewing, hearing and thinking about letters, words and numbers. We describe our method for investigating to what extent synesthetic associations between letters and colors can be learned by reading in color in nonsynesthetes. Reading in color is a special method for training associations in the sense that the associations are learned implicitly while the reader reads text as he or she normally would and it does not require explicit computer-directed training methods. In this protocol, participants are given specially prepared books to read in which four high-frequency letters are paired with four high-frequency colors. Participants receive unique sets of letter-color pairs based on their pre-existing preferences for colored letters. A modified Stroop task is administered before and after reading in order to test for learned letter-color associations and changes in brain activation. In addition to objective testing, a reading experience questionnaire is administered that is designed to probe for differences in subjective experience. A subset of questions may predict how well an individual learned the associations from reading in color. Importantly, we are not claiming that this method will cause each individual to develop grapheme-color synesthesia, only that it is possible for certain individuals to form letter-color associations by reading in color and these associations are similar in some aspects to those seen in developmental grapheme-color synesthetes. The method is quite flexible and can be used to investigate different aspects and outcomes of training synesthetic associations, including learning-induced changes in brain function and structure.

Reading in color is a new method for training letter-color associations that are typically found only in grapheme-color synesthetes. It involves an implicit form of training that has potential for long-term associative training methods&#160;because the training is a byproduct of reading and any text can be colored.

通过读取颜色联觉训练信纸颜色协会

Synesthesia is a rare condition in which a stimulus from one modality automatically and consistently triggers unusual sensations in the same and/or other ...

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 ...

Training Rats to Voluntarily Dive Underwater: Investigations of the Mammalian Diving Response

Underwater submergence produces autonomic changes that are observed in virtually all diving animals. This reflexly-induced response consists of apnea, a parasympathetically-induced bradycardia and a sympathetically-induced alteration of vascular resistance that maintains blood flow to the heart, brain and exercising muscles. While many of the metabolic and cardiorespiratory aspects of the diving response have been studied in marine animals, investigations of the central integrative aspects of this brainstem reflex have been relatively lacking. Because the physiology and neuroanatomy of the rat are well characterized, the rat can be used to help ascertain the central pathways of the mammalian diving response. Detailed instructions are provided on how to train rats to swim and voluntarily dive underwater through a 5 m long Plexiglas maze. Considerations regarding tank design and procedure room requirements are also given. The behavioral training is conducted in such a way as to reduce the stressfulness that could otherwise be associated with forced underwater submergence, thus minimizing activation of central stress pathways. The training procedures are not technically difficult, but they can be time-consuming. Since behavioral training of animals can only provide a model to be used with other experimental techniques, examples of how voluntarily diving rats have been used in conjunction with other physiological and neuroanatomical research techniques, and how the basic training procedures may need to be modified to accommodate these techniques, are also provided. These experiments show that voluntarily diving rats exhibit the same cardiorespiratory changes typically seen in other diving animals. The ease with which rats can be trained to voluntarily dive underwater, and the already available data from rats collected in other neurophysiological studies, makes voluntarily diving rats a good behavioral model to be used in studies investigating the central aspects of the mammalian diving response.

Detailed instructions are provided on how to train rats to voluntarily dive underwater through a 5 m long Plexiglas maze. Because the brains of rats have been very well characterized, voluntarily diving rats may help elucidate the central pathways of the mammalian diving response.

训练大鼠自愿潜水水下:哺乳动物潜水响应调查

Underwater submergence produces autonomic changes that are observed in virtually all diving animals. This reflexly-induced response consists of apnea, a ...

Protocol for Studying Extinction of Conditioned Fear in Naturally Cycling Female Rats

Extinction of conditioned fear has been extensively studied in male rodents. Recently, there have been an increasing number of studies indicating that neural mechanisms for certain behavioral tasks and response behaviors are different in females and males. Using females in research studies can represent a challenge because of the variation of gonadal hormones during their estrous cycle. This protocol describes well-established procedures that are useful in investigating the role of estrogen in fear extinction memory consolidation in female rats. Phase of the estrous cycle and exogenous estrogen administration prior to extinction training can influence extinction recall 24 hr later. The vaginal swabbing technique for estrous phase identification described here aids the examination and manipulation of naturally cycling gonadal hormones. The use of this basic rodent model may further delineate the mechanisms by which estrogen can modulate fear extinction memory in females.

Gonadal hormones such as estrogen modulate memory formation in a number of experimental paradigms including fear extinction memory. This protocol describes a set of methods for investigating the influence of gonadal hormones specifically during extinction in naturally cycling females, including estrous cycle monitoring and exogenous estrogen administration.

协议在骑自行车自然雌性大鼠学习条件性恐惧灭绝

Extinction of conditioned fear has been extensively studied in male rodents. Recently, there have been an increasing number of studies indicating that ...

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 ...

Assessment of Cocaine-induced Behavioral Sensitization and Conditioned Place Preference in Mice

It is thought that rewarding experiences with drugs create strong contextual associations and encourage repeated intake. In turn, repeated exposures to drugs of abuse make lasting alterations in the brain function of vulnerable individuals, and these persistent alterations likely serve to maintain the maladaptive drug seeking and taking behaviors characteristic of addiction/dependence2. In rodents, reward experience and contextual associations are frequently measured using the conditioned place preference assay, or CPP, wherein preference for a previously drug-paired context is measured. Behavioral sensitization, on the other hand, is an increase in a drug-induced behavior that develops progressively over repeated exposures. Since sensitized behaviors can often be measured after several months of drug abstinence, depending on the dose and length of initial exposure, they are considered observable correlates of lasting drug-induced plasticity. Researchers have found these assays useful in determining the neurobiological substrates mediating aspects of addiction as well as assessing the potential of different interventions in disrupting these behaviors. This manuscript describes basic, effective protocols for mouse CPP and locomotor behavioral sensitization to cocaine.

This protocol is intended to enable researchers to conduct experiments designed to test these aspects of addiction using the conditioned place preference and locomotor behavioral sensitization assays.

可卡因诱导行为敏和小鼠位置偏爱评估

It is thought that rewarding experiences with drugs create strong contextual associations and encourage repeated intake. In turn, repeated exposures to ...

A Method for Evaluating the Reinforcing Properties of Ethanol in Rats without Water Deprivation, Saccharin Fading or Extended Access Training

Operant oral self-administration methods are commonly used to study the reinforcing properties of ethanol in animals. However, the standard methods require saccharin/sucrose fading, water deprivation and/or extended training to initiate operant responding in rats. This paper describes a novel and efficient method to quickly initiate operant responding for ethanol that is convenient for experimenters and does not require water deprivation or saccharin/sucrose fading, thus eliminating the potential confound of using sweeteners in ethanol operant self-administration studies. With this method, Wistar rats typically acquire and maintain self-administration of a 20% ethanol solution in less than two weeks of training. Furthermore, blood ethanol concentrations and rewards are positively correlated for a 30 min self-administration session. Moreover, naltrexone, an FDA-approved medication for alcohol dependence that has been shown to suppress ethanol self-administration in rodents, dose-dependently decreases alcohol intake and motivation to consume alcohol for rats self-administering 20% ethanol, thus validating the use of this new method to study the reinforcing properties of alcohol in rats.

This protocol describes a novel and efficient method to quickly initiate operant responding for ethanol in rats that, contrary to standard methods, does not require water deprivation or saccharin/sucrose fading to initiate responding.

一种用于评价大鼠乙醇的补强性能没有禁水，糖精衰落或扩展访问训练方法

Operant oral self-administration methods are commonly used to study the reinforcing properties of ethanol in animals. However, the standard methods ...

Reinstatement of Drug-seeking in Mice Using the Conditioned Place Preference Paradigm

The present protocol describes the Conditioned Place Preference (CPP) as a model of relapse in drug addiction. In this model, animals are first trained to acquire a conditioned place preference in a drug-paired compartment, and after the post-conditioning test, they perform several sessions to extinguish the established preference. The CPP permits the evaluation of the conditioned rewarding effects of drugs related to environmental cues. Then, the extinguished CPP can be robustly reinstated by the non-contingent administration of a priming dose of the drug, and by exposure to stressful stimuli. Both methods will be explained here. When the animal reinitiates the behavioral response, a reinstatement of the conditioned reward is considered to have taken place.
The main advantages of this protocol are that it is non-invasive, inexpensive, and simple with good validity criteria. In addition, it allows the study of different environmental manipulations, such as stress or diet, which can modulate relapse into drug seeking behaviors. However, one limitation is that if the researcher aims to explore the motivation and primary reinforcing effects of the drug, it should be complemented with self-administration procedures, as they involve operant responses of animals.

This protocol describes the Conditioned Place Preference (CPP) as a model of relapse. This procedure permits the measurement of relapse in laboratory animals, considering the impact of drug-associated environmental cues as craving and relapse in abstaining addicts is currently the focus of drug-abuse treatment programs.

用条件位置偏好范式恢复小鼠药物寻毒作用

The present protocol describes the Conditioned Place Preference (CPP) as a model of relapse in drug addiction. In this model, animals are first trained to ...