这些研究是由赠款从加拿大自然科学和工程研究理事会（NSERC）为FL和加拿大研究生奖学金（CGSD）由NSERC到AM.L.支持

1。动物护理及房屋所有的实验都是由圭尔夫大学动物护理委员会批准，并按照加拿大理事会关于动物保护的建议进行的。目前的研究中包括22个成年雄性Sprague-Dawley大鼠（Charles River，QC）称重200-225克在实验的开始。 <ol><li>单家老鼠和维护它们在反向光/暗周期（上午7时关闭 - 下午7:00开）与自由采食获得食物和水除另有指明外，或在此期间，在活动周期发生行为测试。 </li><li>通过术前一周每天称量大鼠习惯于对殖民地的房间和人力搬运。 </li></ol> 2。口腔置管手术：材料与方法口腔内（IO）手术和材料在Limebeer 等 14描述<ol><li>为了营建吨IO套管，切一块聚乙烯塑料管，以大约130毫米的长度（0.86毫米和1.27毫米外径内径）。 </li><li>以在口腔中被固定在管需要一个带凸缘的端部（〜5毫米的直径）。通过加热该管的端部用烙铁为2-5秒，然后迅速地变平对平表面管的加热边创建该凸缘端。切断手术网片（约6-7毫米的直径，以适应周围套管的凸缘端的直径）和线程它在管的长度，直到光盘靠在IO插管的凸缘端的后面。 </li><li>每个IO插管，切开一个额外的手术网圆盘（直径8毫米）和松紧带的三个正方形（6×6mm的，请参阅图1）。 </li><li>消毒IO插管，手术网片，和弹性正方形中为至少24小时之前，手术的抗菌溶液。 </li><li>在手术之前，一utoclave所有手术工具消毒手术野。手术之间，使用玻璃珠灭菌消毒的工具，并戴上发网，丁腈手套，口罩，以保持无菌状态。 </li></ol> 镇痛和麻醉 <ol start="6"><li>手术前约30分钟给药皮下（SC）注射抗生素Depocillin（0.33毫克/千克）和镇痛美洛昔康（5毫克/千克SC）的。 </li><li>用异氟醚（4％诱导和3％维修）诱导全身麻醉。 </li><li>一旦大鼠都没有反应趾压紧，并在作出任何切口之前，使用棉棒棉签施用局部麻醉剂沿大鼠的内左脸颊，其中所述套管是被植入，并且在注射局部麻醉剂如利多卡因盐酸切口部位的活检针（基地颈部）和头帽（头皮）。 </li><li>前激增的开始应用润滑眼膏，以双眼RY。 </li></ol> 外科手术 <ol start="10"><li>剃的头发有10毫米×10毫米的补丁在脖子底部。用无菌纱布，擦拭和清洗按以下顺序剃光面积：抗菌肥皂，异丙醇70％的酒精，和聚维酮碘。 </li><li>插入15政不锈钢针在颈部的基部和皮下移动它的耳朵到左脸颊。定位针尖，并通过口腔内第一磨牙后面的脸颊传递给它。 </li><li>通过针从口腔突出的尖端通过IO套管，然后取出针只剩下IO套管。 </li><li>线程一个外科网盘由三个正方形弹性光盘上的IO套管的外部分，并将其绘制到裸露的皮肤在脖子后面以使其稳定。 </li><li>冲洗的IO套管用抗菌漱口</li><li>手术前的开始，修改尼龙螺栓（28 mm长;4毫米点，8 mm头），以去除其头部和雕刻2毫米的凹槽沿着螺纹的长度（ 见图2）。 </li><li>剃的头发10毫米×20毫米长条沿头部中线。用无菌纱布，擦拭和清洗按以下顺序剃光面积：抗菌肥皂，异丙醇70％的酒精，和聚维酮碘。 </li><li>用外科手术刀做一个20mm长的切口，沿矢状缝。使用手电钻，使4个孔（2对缝线的每一侧），并使用一个手持螺丝刀固定4螺丝珠宝商的头骨。 </li><li>放置在螺栓中的四个珠宝商螺钉的中心位置朝向动物的后部的凹槽中。通过构建一个headcap牙科水泥（使用足够的牙科水泥覆盖的珠宝商螺丝表面）安装螺栓，以大鼠的头骨。使牙科用粘固剂，从手术区域去除动物之前干燥和终止麻醉。 </li></ol><p类=“jove_content”&gt; 术后的监测和护理 <ol start="19"><li>单独房子大鼠床笼后立即手术，并密切监测24小时。 </li><li>施用第二次注射的镇痛美洛昔康后24小时的手术和冲洗套管的IO用三天一种抗菌漱口，一次/天。 </li></ol>给大鼠3-5天从手术前的实验开始恢复。 3。 IO自我管理程序 设备 对于自我给药，有机玻璃操作性条件腔室的使用，并且每个腔室是封闭在一个较大的声音衰减胶合板箱。每个操作条件腔室具有一所房子的光（28伏）和两个可伸缩的杆（有效和无效的），其位于所述腔室的相对侧上8厘米以上的地板。主动杆连接到输液泵设置出局IDE中的隔音室和一个白色的光（28瓦）位于3厘米​​它上面以作为成对的IO输注递送的刺激​​光。不活跃的杠杆作用是控制基线，无钢筋操作行为;按下此杆有没有结果，但所有印刷机都记录。 食物 <ol><li>提供大鼠标准大鼠饲料（3.1千卡/克），在他们的家笼。 </li><li>稀释高果糖玉米糖浆（55％式），以三种不同浓度（8％）=（0.026 kcal/80微升注入50％= 0.17 kcal/80微升注入25％= 0.08 kcal/80微升输注）使用反渗透水。这些浓度被选择，因为每个产生的粘度是适合提供快速给出的实验装置（注射器和管即直径）（2.5秒）的IO输注。 </li></ol> 粮食匮乏 为了便于收购IO自治，但促进正常生长，大鼠通过食物匮乏和随意接近标准大鼠饲料的循环周期。 <ol start="3"><li>每天称量大鼠下午7点，并从笼料桶删除州城。 </li><li>次日，大鼠体重在下午12:00（约18小时后）和下午1:00开始的IO自我管理。 </li><li>返回大鼠饲养笼下午4:00，并提供自由采食访问州城连续3小时。然后，记录大鼠的体重和饲料消耗超过三个小时的总量。所述恢复粮食匮乏。 </li></ol> 一般IO自我管理程序 操作性为应对高果糖浆的IO输注评估公关及钢筋连续时间表。大鼠在IO自我管理测试，直到摄入量是由稳定的定义：在主动和INAC之间的响应一）一个显著差异略去杠杆至少连续2届，2）在每节赢得了连续2届输注的次数少于20％的变化。每个会话开始6小时到黑暗周期，持续3个小时。采集阶段包括对钢筋的连续时间表连续10个IO自我管理会话，和老鼠获得一个PR测试24小时前收购的开始（PR试验I）和24小时的最后收购阶段（PR测试后二）。对于PR的测试中，该断点（BP）被定义为之前停止响应于主动杆为至少1小时18接收到的最后一次输注。 <ol start="6"><li>抗衡大鼠在实验开始前，采取了三天，并指派大鼠进行自我管理三个浓度高果糖浆中的一个权重的基础上：8％，25％，或50％。 </li><li>称取大鼠在下午12:00从殖民地房间他们转移到考场在他们的家笼。而去除食物或beddi纳克能够积聚在IO套管，通过套管使用12毫升注射器固定带16号针头与连接到端50毫米聚乙烯管（1.14毫米和1.57毫米外直径的内直径）的空气泵。 </li><li>在操作性室，通过修改后的20 G针（去掉塑料轴套和斜面尖端）的构造轴的IO套管连接聚乙烯管（0.02毫米和1.53毫米外径内径）。定位在管的下部的螺栓的树林内（ 即靠近动物）。管子的较大部分被连接到一个旋转，并通过一个弹簧保护。弹簧的基座连接到安装在鼠的头部螺栓的螺纹。 </li><li>给大鼠五分钟使其恢复到操作性室，然后开始对IO自我管理会话。在IO自我管理会话开始与房子的光，进入两个可伸缩的杆，以及照明的活化光刺激的积极杠杆，持续30秒以上。 </li><li>公关测试I，使用由Richardson和Roberts18描述的公关时间表（响应比升级=（5 E（注射数×0.2）） - 5）。 </li><li>对于收购会话1-10，使用强化的连续时间表，据此，记者在活动杆成绩超过2.5秒供试品溶液80μL注入的交付。 </li><li>为预留足够的时间摄取，并处以27.5秒的超时周期在此期间，主动杆缩回并刺激光被激活（ 即鼠可以得到一个IO滴注，每30秒）。勿施于输液每个IO自我管理会话中获得的数量进行限制。 </li><li>如果老鼠不作出回应于主动杆连续20分钟，黄金鼠（打开操作性室，并促进大鼠在活动杆压一次）。总理的动物，每20分钟高达5x/session杜只响收购的前三天。 </li><li>使用步骤3.10中描述的参数管理第二公关考验。 </li><li>以下IO自我管理会话，从操作室取出大鼠中，用2.0ml水使用在3.7中描述的相同的材料冲洗IO插管，并返回到大鼠中的菌落室他们的家笼中。 </li><li>以下三个小时的自由采食访问大鼠饲料，大鼠体重下午7:00，从饲槽取出食物，并恢复食物匮乏。 </li></ol>自我管理数据采用方差分析（ANOVA）两因素重复测量分析分析。使用学生 - 纽曼 - Keuls检验法（α= 0.05）多重比较来探索任何显著相互作用或主要作用。

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Neurosci. 22 (9), 3306-3311 (2002).</li><li>Shaham, Y., Shalev, U., Lu, L., De Wit, H., Stewart, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+reinstatement+model+of+drug+relapse:+history,+methodology+and+major+findings.">The reinstatement model of drug relapse: history, methodology and major findings.</a> Psychopharmacology. 168 (1-2), 3-20 (2003).</li><li>de Wit, H., Stewart, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Drug+reinstatement+of+heroin-reinforced+responding+in+the+rat.">Drug reinstatement of heroin-reinforced responding in the rat.</a> Psychopharmacology. 79 (1), 29-31 (1983).</li><li>Schmidt, H. D., Anderson, S. M., Famous, K. R., Kumaresan, V., Pierce, R. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Anatomy+and+pharmacology+of+cocaine+priming-induced+reinstatement+of+drug+seeking.">Anatomy and pharmacology of cocaine priming-induced reinstatement of drug seeking.</a> Eur. J. Pharmacol. 526 (1-3), 65-76 (2005).</li><li>Dunnigan, M. G., Ford, J. S. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+insulin+response+to+intravenous+fructose+in+relation+to+blood+glucose+levels.">The insulin response to intravenous fructose in relation to blood glucose levels.</a> J. Clin. Endocrinol. Metab. 40 (4), 629-635 (1975).</li><li>Crapo, P. A., Kolterman, O. G., Olefsky, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+oral+fructose+in+normal,+diabetic,+and+impaired+glucose+tolerance+subjects.">Effects of oral fructose in normal, diabetic, and impaired glucose tolerance subjects.</a> Diabetes Care. 3 (5), 575-582 (1980).</li><li>L&#234;, K. A., Tappy, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Metabolic+effects+of+fructose.">Metabolic effects of fructose.</a> Curr. Opin. Clin. Nutr. Metab. Care. 9 (4), 469-475 (2006).</li><li>Scheggi, M. E., Secci, G., Marchese, M. G., De Montis, C., Gambarana, <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Influence+of+palatability+on+motivation+to+operate+for+caloric+and+non-caloric+food+in+non+food-deprived+and+food-deprived+rats.">Influence of palatability on motivation to operate for caloric and non-caloric food in non food-deprived and food-deprived rats.</a> Neuroscience. 236, (2013).</li><li>Sclafani, A., Lucas, F., Ackroff, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+importance+of+taste+and+palatability+in+carbohydrate-induced+overeating+in+rats.">The importance of taste and palatability in carbohydrate-induced overeating in rats.</a> Am. J. Physiol. 270 (6), 1197-1202 (1996).</li><li>Roberts, D. C. S., Loh, E. A., Vickers, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Self-administration+of+cocaine+on+a+progressive+ratio+schedule+in+rats:+dose-response+relationship+and+effect+of+haloperidol+pretreatment.">Self-administration of cocaine on a progressive ratio schedule in rats: dose-response relationship and effect of haloperidol pretreatment.</a> Psychopharmacology. 97 (4), 535-538 (1989).</li><li>Reilly, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reinforcement+value+of+gustatory+stimuli+determined+by+progressive+ratio+Performance.">Reinforcement value of gustatory stimuli determined by progressive ratio Performance.</a> Pharmacol. Biochem. Behav. 63 (2), 301-311 (1999).</li><li>Zittel-Lazarini, A., Cador, M., Ahmed, S. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+critical+transition+in+cocaine+self-administration:+Behavioral+and+neurobiological+implications.">A critical transition in cocaine self-administration: Behavioral and neurobiological implications.</a> Psychopharmacology. 192 (3), 337-146 (2007).</li><li>Stanhope, K. L., Havel, P. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Endocrine+and+metabolic+effects+of+consuming+beverages+sweetened+with+fructose,+glucose,+sucrose,+or+high+fructose+corn+syrup+Am.">Endocrine and metabolic effects of consuming beverages sweetened with fructose, glucose, sucrose, or high fructose corn syrup Am.</a> J. Clin. Nutr. 88 (6), 17335-17375 (2008).</li><li>Deroche-Gamonet, V., Belin, B., Piazza, P. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evidence+for+addiction-like+behaviour+in+the+rat.">Evidence for addiction-like behaviour in the rat.</a> Science. 305, 1014-1017 (2004).</li></ol>

有没有透露作者。

目前的研究显示了一种新的方法相结合，采用传统的学习行为由滥用药物（静脉操作性自我管理）的积极性，并评估促味剂的适口性（通过口内注射味道的反应）方法评估甜美解决方案的增强特性。为此，非常简短的异氟烷诱导麻醉下，将大鼠植入一个IO套管，其允许输送试验溶液直接进入他们的嘴。以下从手术恢复，将动物在操作性自我给药试验室，由此他们可以按杠杆得到试验溶液的IO输注。...

上瘾食物的神经生物学和行为基础的研究依赖于，类似于滥用药物，过量食用可口食物，促进行为的依赖1-4的意见和诱导改变大脑奖赏回路在人和5-6和实验室动物7-8。但是，尽管有几个协议和用于研究的药物滥用在实验室老鼠的成瘾性，以适应这些方法来评估由食物诱发提出了独特的挑战“上瘾”的行为过程。本研究的目的是要操作性静脉注射（IV）药物的自我管理的原则，适用于口内（IO）输液甜交付解决方案的操作性自我管理的调查。甜蜜采用了高果糖玉米糖浆（HFCS），因为尽管有争议，有证据表明，高果糖浆可能与肥胖9-12的现代流行病。 传统上，IO输注交付研究促味剂的适口性味觉反应的实验13。简单地说，一个IO插管手术植入到大鼠和各种解决方案的IO输注的脸颊是被动地交付了14。的目标是研究动物的口面部反应的促味剂。然而，IO插管也已经长期植入大鼠腭，以确定它们是否会学习按杠杆自行INFUSE解决方案直接到他们的口腔内，因此这个词的IO自行注射15-17。在目前的研究中，我们描述了利用小手术并允许长期操作性自我给药试验的过程。这个程序拥有涉及从壶嘴（一），或操作性回应固体颗粒喝了解决方案，传统的程序几个显著的优势（二），或操作性回应流体在一个容器交付滴（三）。 相比于（a）中，IO自行给药涉及一个操作反应（ 即按压杠杆），因此它可以修改调度调节响应的要求和提供的IO输注之间的关系。例如，通过采用累进比（PR）的时间表，由此需要连续输注反应的会话18内成倍增加，能够以评估多少动物“要”的下一个输注19。当动物喝从壶嘴的解决方案，除非它控制流体输送及监控响应一个特殊的装置，采用20这个重要的“求”的行为方面无法评估。此外，IO自我管理提供了一个平均值进行比较的行为由不同的强化刺激的动机。也就是说，它可以比较操作性由糖果和其它增强剂，如滥用药物在应对维护所谓的“替代研究。” 相比于（b）所示，IO自行给药允许任何浓度的测试和任何水溶性食品添加剂的任何体积。因为，在我们所知，有果糖没有市售的固体颗粒或以不同比例的果糖，葡萄糖组合，这是非常重要的学习行为由甜食，如高果糖浆的动机，那将是适合于操作室。此外，控制和操纵浓度/体积比的重要性是强制性的实验中摄取既可以通过溶液（导致营养物特异性的饱腹感）的热值和由该如何解决的多少可以在给定的消耗来调制一段时间后（ 即丰满）21。 IO自我管理也缩短了操作反应和传递的主要增强剂，即起着收购和维护具有重要作用的一个因素之间的延迟南切操作行为16,22-23。 最后，在比较（c）中，IO自我管理允许受控的试验溶液的量的被动IO输注递送，并且这使得可以测量“喜欢”的口面的反应（目标享乐反应如舌突起24 -25）和IO是否自我管理过程中这些反应改变。此外，管理被动的IO输注的能力有复发的食物寻求学习显著应用。也就是说，在静脉注射毒品的自我管理的研究，以下灭绝的时期，素药物（小剂量药物26 即管理）可以“恢复”响应27-28。因此，提供的IO输注而对动物的任何行动的能力，可用于研究“食”引复职，以及潜在的交叉复职食物之间滥用药物。 甜美的解决方案IO自我管理也是可取的IV和胃内自我管理。事实上，虽然果糖在人类和实验动物静脉注射产生的生理后果类似的观察口服消费29-31，这是甜食是如何正常消耗（ 即口服）一个贫穷的模型。此外，通过咀嚼产生的味觉信号赋予有关食物的适口性的重要信息，而当省略这个阶段的消化过程，适应不良行为，如暴饮暴食的发展降低了32-33。

<table border="1">
 <tbody>
 <tr>
 <td></td>
 <td></td>
 <td></td>
 <td>Reagents</td>
 </tr>
 <tr>
 <td>Meloxicam</td>
 <td>Boehringer Ingelheim Canada Ltd.</td>
 <td></td>
 <td>From the Ontario Veterinary College pharmacy</td>
 </tr>
 <tr>
 <td>Procaine Penicillin G</td>
 <td>Pen Aqueous, Wyeth Animal Health</td>
 <td></td>
 <td>From the Ontario Veterinary College pharmacy</td>
 </tr>
 <tr>
 <td>Lidocaine HCl 2%</td>
 <td></td>
 <td></td>
 <td>From the Ontario Veterinary College pharmacy</td>
 </tr>
 <tr>
 <td>Marcaine 0.5 %</td>
 <td></td>
 <td></td>
 <td>From the Ontario Veterinary College pharmacy</td>
 </tr>
 <tr>
 <td>Lubricating eye ointment</td>
 <td></td>
 <td></td>
 <td>Product can be bought at any pharmacy</td>
 </tr>
 <tr>
 <td>2% Lidocaine Viscous Oral (Topical Anesthetic)</td>
 <td>Pharmascience Inc.</td>
 <td>CDMV # 14705</td>
 <td>100 ml bottle</td>
 </tr>
 <tr>
 <td>Isoflurane USP</td>
 <td>Pharmaceutical Partners of Canada</td>
 <td>CDMV # 108737</td>
 <td>250 ml bottle</td>
 </tr>
 <tr>
 <td>Bacti-Stat</td>
 <td>Merck Sante Animale</td>
 <td>CDMV # 6449</td>
 <td>3.785 L bottle</td>
 </tr>
 <tr>
 <td>Isopropyl alcohol (70%)</td>
 <td>Perdu Pharma</td>
 <td>Fisher # MPX18404</td>
 <td>4 L bottle</td>
 </tr>
 <tr>
 <td>Betadine 10%</td>
 <td>McKesson Canada</td>
 <td>CDMV # 104826</td>
 <td>500 ml bottle</td>
 </tr>
 <tr>
 <td>Super Germiphene</td>
 <td>Ceva Animal Health</td>
 <td>CDMV # 103629</td>
 <td>454 ml bottle</td>
 </tr>
 <tr>
 <td>Chlorhexidene(Novadent)</td>
 <td>Zoetis</td>
 <td>CDMV # 8908</td>
 <td>236 ml bottle</td>
 </tr>
 <tr>
 <td>High Fructose Corn Syrup</td>
 <td>Natures Flavours</td>
 <td>HFCS-55</td>
 <td>1 Gallon bottle</td>
 </tr>
 <tr>
 <td></td>
 <td></td>
 <td></td>
 <td>Materials</td>
 </tr>
 <tr>
 <td>PE90 tubing</td>
 <td>Becton Dickinson and Company</td>
 <td>VWR # CA-63019-080A</td>
 <td>100 ft/coil</td>
 </tr>
 <tr>
 <td>PE160 tubing</td>
 <td>Becton Dickinson and Company</td>
 <td>VWR # CA-63018-747</td>
 <td>100 ft/coil</td>
 </tr>
 <tr>
 <td>Polypropylene Mesh</td>
 <td>Small Parts Inc.</td>
 <td>CMP-0297-D</td>
 <td></td>
 </tr>
 <tr>
 <td>Soldering iron</td>
 <td></td>
 <td></td>
 <td>Product can be bought at any hardware store</td>
 </tr>
 <tr>
 <td># 64 Elastic bands</td>
 <td>Staples Office supplies</td>
 <td>Item # 13556</td>
 <td>Product can be bought at any office supply store</td>
 </tr>
 <tr>
 <td>15 G thin-walled 3.5 inch needles</td>
 <td></td>
 <td>VWR # CABD1108</td>
 <td>12 needles per pack</td>
 </tr>
 <tr>
 <td>Electric razor (1/2 in wide blade)</td>
 <td></td>
 <td></td>
 <td>Product can be bought at any pet supply store</td>
 </tr>
 <tr>
 <td>Percision Glide Needles 20 G needles (1 &frac12; in)</td>
 <td>Becton Dickinson and Company</td>
 <td>Fisher # 14-826D</td>
 <td></td>
 </tr>
 <tr>
 <td>Percision Glide Needles 16 G needles (1 &frac12; in)</td>
 <td>Becton Dickinson and Company</td>
 <td>Fisher # 14-826-5D</td>
 <td></td>
 </tr>
 <tr>
 <td>Operant conditioning chambers</td>
 <td>Med Associates Inc.</td>
 <td>ENV-008-CTC</td>
 <td></td>
 </tr>
 <tr>
 <td>Sound attenuating chamber</td>
 <td>Med Associates Inc.</td>
 <td>ENV-018M</td>
 <td></td>
 </tr>
 <tr>
 <td>MED PC IV software</td>
 <td>Med Associates Inc.</td>
 <td>SOF-735</td>
 <td></td>
 </tr>
 <tr>
 <td>Syringe Pumps</td>
 <td>Razel Scientific Instruments</td>
 <td></td>
 <td></td>
 </tr>
 <tr>
 <td>Disposable plastic swivel assembly</td>
 <td>Med Associates Inc.</td>
 <td>PHM-115I</td>
 <td></td>
 </tr>
 <tr>
 <td>Tygone Microbore tubing</td>
 <td>Saint Gobain Performance Plastics</td>
 <td>Fisher # 1417015B</td>
 <td>500 ft/coil</td>
 </tr>
 </tbody>
</table>

a novel procedure for evaluating the reinforcing properties of tastants in laboratory rats: operant intraoral self-administration

本文介绍了一种新方法研究瘾食物的生物行为的基础。这种方法结合了味道的反应与药物操作性自我管理的行为方面的手术成分。在非常短暂的全身麻醉，将大鼠植入口腔内（IO），插管直接允许在口腔内递送的测试解决方案。然后将动物的操作性自我管理室测试，使他们能够按杠杆接收测试解决方案的IO输注。 IO自我管理方面拥有逾涉及饮用从一个喷口或操作性回应固体颗粒或在容器交付解决方案解决实验过程的几个优点。这里，我们表明，IO自行给药可用于研究的高果糖玉米糖浆（HFCS）自我给药。大鼠首先测试的自我管理上的一个进步率（PR）的日程安排，评估运算的最高金额erant行为，将不同浓度高果糖浆（ 即 8％，25％和50％）的发射。下面这个测试，大鼠自我管理这些浓度对加固连续时间表（ 即，一个输液每个杆出版社），连续10天（1次/天;每次持续3小时），然后他们再次接受测试的公关时间表。在连续加固时间表，大鼠把高浓度的减少输注，虽然高果糖浆的最低浓度（8％）保持更可变的自我管理。此外，在PR测试显示，8％有下部加强值超过25％和50％。这些结果表明，IO自我给药可以用来研究获得和维持响应于甜的解决方案。在浓度和加固进度差异的操作反应的灵敏度使得IO自我管理的理想方法研究自由采食量的神经生物学Õf甜食。

收购IO自我管理 图3表示操作性期间的8％，25％，或50％高果糖浆，连续10届自我管理的有效和无效的杠杆回应。大鼠获得高果糖浆的IO自我管理的前三个阶段内，并保持稳定的主动杆响应（如上所述），以收购的其余部分。在主动杆响应的浓度依赖性的差异也很明显：相比于25％时，响应是显著降低大鼠个体施用50％高果糖浆。测试的最低浓度（8％）保持操?...

Watch this Scientific Journal Video about A Novel Procedure for Evaluating the Reinforcing Properties of Tastants in Laboratory Rats: Operant Intraoral Self-administration at JoVE.com

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

目前的研究评估了一种新的程序，以评估可口的解决方案在实验室老鼠的增强作用：口内的自我管理。为此，操作性响应（ 即杠杆按压），用于甜的解决方案在不同浓度的口腔内输注上测量钢筋连续和渐进比时间表。

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 ...

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12.6K 次观看.  University of Guelph. 目前的研究评估了一种新的程序，以评估可口的解决方案在实验室老鼠的增强作用：口内的自我管理。为此，操作性响应（ 即杠杆按压），用于甜的解决方案在不同浓度的口腔内输注上测量钢筋连续和渐进比时间表。 

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

Use of the Operant Orofacial Pain Assessment Device (OPAD) to Measure Changes in Nociceptive Behavior

We present an operant system for the detection of pain in awake, conscious rodents. The Orofacial Pain Assessment Device (OPAD) assesses pain behaviors in a more clinically relevant way by not relying on reflex-based measures of nociception. Food fasted, hairless (or shaved) rodents are placed into a Plexiglas chamber which has two Peltier-based thermodes that can be programmed to any temperature between 7 &deg;C and 60 &deg;C. The rodent is trained to make contact with these in order to access a reward bottle. During a session, a number of behavioral pain outcomes are automatically recorded and saved. These measures include the number of reward bottle activations (licks) and facial contact stimuli (face contacts), but custom measures like the lick/face ratio (total number of licks per session/total number of contacts) can also be created. The stimulus temperature can be set to a single temperature or multiple temperatures within a session. The OPAD is a high-throughput, easy to use operant assay which will lead to better translation of pain research in the future as it includes cortical input instead of relying on spinal reflex-based nociceptive assays.

Use of the Operant Orofacial Pain Assessment Device OPAD to Measure Changes in Nociceptive Behavior

We present a user-friendly, high-throughput operant system for the evaluation of pain behaviors in awake, conscious rodents. The Orofacial Pain Assessment Device (OPAD) can assess pain through a reward/conflict paradigm thus providing a more humane way of testing. This protocol will yield more clinically relevant and translational data from rodents.

使用操作性口面疼痛评估设备（OPAD）测量伤害行为的变化

We present an operant  system for the detection of pain in awake, conscious rodents. The Orofacial  Pain Assessment Device (OPAD) assesses pain behaviors ...

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 ...

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 ...

Operant Procedures for Assessing Behavioral Flexibility in Rats

Executive functions consist of multiple high-level cognitive processes that drive rule generation and behavioral selection. An emergent property of these processes is the ability to adjust behavior in response to changes in one&#8217;s environment (i.e., behavioral flexibility). These processes are essential to normal human behavior, and may be disrupted in diverse neuropsychiatric conditions, including schizophrenia, alcoholism, depression, stroke, and Alzheimer&#8217;s disease. Understanding of the neurobiology of executive functions has been greatly advanced by the availability of animal tasks for assessing discrete components of behavioral flexibility, particularly strategy shifting and reversal learning. While several types of tasks have been developed, most are non-automated, labor intensive, and allow testing of only one animal at a time. The recent development of automated, operant-based tasks for assessing behavioral flexibility streamlines testing, standardizes stimulus presentation and data recording, and dramatically improves throughput. Here, we describe automated strategy shifting and reversal tasks, using operant chambers controlled by custom written software programs. Using these tasks, we have shown that the medial prefrontal cortex governs strategy shifting but not reversal learning in the rat, similar to the dissociation observed in humans. Moreover, animals with a neonatal hippocampal lesion, a neurodevelopmental model of schizophrenia, are selectively impaired on the strategy shifting task but not the reversal task. The strategy shifting task also allows the identification of separate types of performance errors, each of which is attributable to distinct neural substrates. The availability of these automated tasks, and the evidence supporting the dissociable contributions of separate prefrontal areas, makes them particularly well-suited assays for the investigation of basic neurobiological processes as well as drug discovery and screening in disease models.

The ability to assess executive functions such as behavioral flexibility in rats is useful for investigating the neurobiology of cognition in both intact animals and disease models. Here we describe automated tasks for assessing strategy shifting and reversal learning, which are particularly sensitive to disruptions in prefrontal cortical networks.

操作性程序，以评估大鼠的行为灵活性

Executive functions consist of multiple high-level cognitive processes that drive rule generation and behavioral selection. An emergent property of these ...

A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration

Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people. There is a need for novel, effective and practical treatment strategies that are validated in animal models. Neuromodulation, including deep brain stimulation (DBS) therapy, refers to the use of electricity to influence pathological neuronal activity and has shown promise for psychiatric disorders, including drug dependence. DBS in clinical practice involves the continuous delivery of stimulation into brain structures using an implantable pacemaker-like system that is programmed externally by a physician to alleviate symptoms. This treatment will be limited in methamphetamine users due to challenging psychosocial situations. Electrical treatments that can be delivered intermittently, non-invasively and remotely from the drug-use setting will be more realistic. This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence. Methamphetamine dependence is rapidly developed in rodents using an operant paradigm of intravenous (IV) self-administration that incorporates a period of extended access to drug and demonstrates both escalation of use and high motivation to obtain drug.

This article describes the delivery of intracranial electrical stimulation that is temporally and spatially separate from the drug-use environment for the treatment of IV methamphetamine dependence.

一般方法评估对静脉注射甲基苯丙胺的自我管理深部脑刺激的影响

Substance use disorders, particularly to methamphetamine, are devastating, relapsing diseases that disproportionally affect young people.  There is a need ...

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 ...

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 ...

Three Laboratory Procedures for Assessing Different Manifestations of Impulsivity in Rats

The present article provides a guide for the conduction and analysis of three conditioning-based protocols to evaluate impulsivity in rats. Impulsivity is a meaningful concept because it is associated with psychiatric conditions in humans and with maladaptive behavior in non-human animals. It is believed that impulsivity is composed of separate factors. There are laboratory protocols devised to assess each of these factors using standardized automated equipment. Delay discounting is associated with the incapacity to be motivated by delayed outcomes. This factor is evaluated through intertemporal choice protocols, which consist&#160;of presenting the individual with a choice situation involving an immediate reward and a larger but delayed reward. Response inhibition deficit is associated with the incapacity to withhold prepotent responses. Differential reinforcement of low rates (DLR) and feature-negative discrimination protocols assess the response inhibition deficit factor of impulsivity. The former imposes a condition to a motivated individual in which most wait a minimum period of time for a response to be rewarded. The latter evaluates the capacity of individuals to refrain from food seeking responses when a signal of the absence of food is presented. The purpose of these protocols is to construct an objective quantitative measure of impulsivity, which serves to make cross-species comparisons, allowing the possibility of translational research. The advantages of these particular protocols include their easy set-up and application, which stems from the relatively small amount of equipment needed and the automated nature of these protocols.

We present three protocols that assess different forms of impulsivity in rats and other small mammals. Intertemporal choice procedures evaluate the tendency to discount the value of delayed outcomes. Differential reinforcement of low rates and feature-negative discrimination evaluate response inhibition capacity with and without punishment for inappropriate responses, respectively.

评估大鼠冲动不同表现的三个实验室程序

The present article provides a guide for the conduction and analysis of three conditioning-based protocols to evaluate impulsivity in rats. Impulsivity is ...

A Laboratory Method to Measure Contagious Yawning in Rats

Communication is an essential aspect of animal social life. Animals may influence one another and come together in schools, flocks, and herds. Communication is also the way sexes interact during courtship and how rivals settle disputes without fighting. However, there are some behavioral patterns for which it is difficult to test the existence of a communicatory function, because several types of sensory modalities are likely involved. For example, contagious yawning is a communicatory act in mammals that potentially occurs through sight, hearing, smell, or a combination of these senses depending on whether the animals are familiar to one another. Therefore, to test hypotheses about the possible communicatory role of such behaviors, a suitable method is necessary to identify the participating sensory modalities.
The method proposed here aims to obtain yawn contagion curves for familiar and unfamiliar rats and evaluate the relative participation of visual and olfactory sensory modalities. The method uses inexpensive materials, and with some minor changes, it can also be used with other rodent species such as mice. Overall, the method involves the substitution of clear dividers (with or without holes) with opaque dividers (with or without holes) that either allow or prevent communication between rats placed in adjacent cages with holes in adjoining sides. Accordingly, four conditions can be tested: olfactory communication, visual communication, both visual and olfactory communication, and neither visual nor olfactory communication. As social interaction occurs between the rats, these test conditions simulate what may occur in a natural environment. In this respect, the method proposed here is more effective than traditional methods that rely on video presentations whose biological validity can raise concerns. Nonetheless, it does not discriminate between the potential role of hearing and roles of smell and vision in yawn contagion.

The method described here aims to obtain yawn contagion curves in pairs of familiar or unfamiliar male rats. Cages with holes separated by either clear or opaque partitions with (or without) holes are used to detect whether visual, olfactory, or both types of sensory cues can stimulate yawn contagion.