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
Summary
本协议描述为一种新型快捷的方法来快速启动操作性的，相反，标准方法，不需要水剥夺或糖精/蔗糖衰落的开始响应响应大鼠乙醇。
Abstract
操作性口服自我施用方法通常用于研究的动物的乙醇补强性。然而，标准方法需要糖精/蔗糖衰落，禁水和/或延长培训发起操作性大鼠响应。本文介绍一种新颖且有效的方法来快速启动操作性响应的乙醇也方便实验者和不需要水剥夺或糖精/蔗糖衰落，从而消除在乙醇操作性自我施用研究使用甜味剂的电位变乱。用这种方法，将Wistar大鼠通常获得并维持20％的乙醇溶液的自我施用在不到两周的训练。此外，血液中乙醇浓度和奖励一个30分钟的自我管理会话是正相关的。此外，纳曲酮，已被证明酒精依赖FDA批准的药物来抑制乙醇的自我管理在啮齿动物，剂量依赖性减少酒精摄入和动力消耗对大鼠自我施用20％乙醇的醇，从而验证使用这种新方法的研究在大鼠醇的补强性能。
Introduction
动物模型来研究药物的增强效果的发展已经证明研究人类药物成瘾的重要工具。更具体地，操作性自我施用是一种广泛使用的行为模型，这是最有效的手段，以评估口服消耗乙醇溶液的阳性增强效果之一。与开发这样一个模型的早期问题是高浓度的乙醇对大多数鼠类主厌恶味道，即，可以在与醇1很少或没有经验的人类共享的现象。一个标准的协议来克服这一障碍需要禁水和/或糖精或蔗糖衰落收购和自我管理的维护。然而，这两种方法都不是有利的。他们需要的培训长时间简单地启动响应为乙醇和收购取得的相对成功率。使用甜味剂还引入了一个潜在的偏见自我管理数据的解释。这些限制并不适用于以下协议。
简单地说，参孙和同事2表明，溶解在20％蔗糖的甜美乙醇溶液中，然后在4周的训练淡出了甜头需要发起水响应的10％的乙醇。此外，可靠乙醇摄入6至8周1-3通常实现。这种方法是很成问题。首先，它要求的训练长时间之前研究者可以开始测量乙醇自身给药。相比之下，可卡因或海洛因静脉自身给药需要0 -在限食动物食品提供杠杆药物前培训1天，稳定的响应药物通常是在10实现- 1天4,5。该方法的另一限制是，糖精和蔗糖是高度有益的大鼠和引发脑激活图形Similar滥用药物，从而带来了潜在的的困惑在乙醇的自我管理研究6-9。最后，由于不成功的采集和/或应答率不足大鼠取得使用在获得和反应率1,10-此方法显示变性的乙醇溶液，与实验一致排除大鼠相当比例的自我给药。
相比之下，有此协议，我们提出收购，并在水中的解决方案，并不需要禁水，蔗糖/糖精的衰落和扩展访问培训20％乙醇的口腔自我管理维护一个简单而有效的方法。最近的调查发现，在20％的乙醇浓度的自我管理期间，自我给药用于口服乙醇显示具有最高乙醇摄取一个倒U形的剂量反应曲线，从而为在我们的experim选择20％的乙醇溶液中提供理ental设计11。
Protocol
所有程序都符合美国国立卫生研究院指南实验动物的护理和使用进行。 1.动物护理和房屋当在菌落到来，房子的雄性Wistar大鼠，体重200 – 在一个温度（21℃）和湿度控制的环境有一个扭转12小时明暗周期到达成对225克。 注：根据实验的基本原理，老鼠可以是单住。 允许大鼠适应环境的动物饲养和光周期为至少一个星期开始实验之前和每天处理它们。称量动物每周一次。 </…
Representative Results
图1显示了operant-和药物天真大鼠代表自我管理行为（八个不同的队列数额总计为239只）训练了FR1时间表进行自我管理20％乙醇停水剥夺或糖精/蔗糖衰落在30分钟的会议。有了这个协议，只启动杆挤压很快得到乙醇的奖励，已经获得第一届（ 图1A）在10多个奖励。它们通过自我管理的会议10到达上主动杆稳定响应率，从而获得的在FR1（ 图1B）23….
Discussion
有了这个协议，我们提出一种新的方法来获得并维持20％乙醇的稳定口服自我管理的，相反，乙醇自我管理的经典机型，不需要使用禁水，扩展访问训练大鼠，或糖精/蔗糖衰落12。此外，纳曲酮，当前FDA批准用于酒精依赖药物治疗，成功地降低酒精的自我管理和消费这一协议训练有素的Wistar大鼠酒精的动机。这个结果提供了协议的一个重要的药理学验证，因为它是与表示纳曲酮是有效减少…
Divulgazioni
The authors have nothing to disclose.
Acknowledgements
这项工作是由瑞典研究理事会的支持。
Materials
| Extra Tall MDF Sound Attenuating Cubicle, Interior: 22"W x 22"H x 16"D | Med Associates Inc. | ENV-018MD | |
| Extra Tall Modular Test Chamber with modified Top, Waste Pan and Photobeam | Med Associates Inc. | ENV-007CT-PH | |
| Stainless Steel Grid Floor for Rat or Small Primate | Med Associates Inc. | ENV-005 | |
| Retractable Lever | Med Associates Inc. | ENV-112CM | 2 by SA chambers |
| Stimulus Light, 1" White Lens, Mounted on Modular Panel | Med Associates Inc. | ENV-221M | 2 by SA chambers |
| Dual Cup Liquid Receptacle with 18ga Stainless Steel Pipes | Med Associates Inc. | ENV-200R3AM | |
| Single Speed Syringe Pump, 3.33RPM | Med Associates Inc. | PHM-100 | |
| Liquid Delivery Kit | Med Associates Inc. | PHM-122-18 | |
| SmartCtrl 8 Input, / 16 Output Package | Med Associates Inc. | DIG-716P2 | |
| MED-PC software | Med Associates Inc. | SOF-735 | |
| http://www.mednr.com/ | Med Associates Inc. | A website that is open-source and has been created to offer researchers a place to exchange MEDState Notation code | |
| Kendall Monoject 20cc Syringes, Regular Luer Tip | VWR International | MJ8881-520657 | |
| Ethanol, Pure, 190 Proof (95%), USP, KOPTEC | Decon Labs | 2801 | |
| 0.9% Sodium Chloride Injection, USP | Hospira | 0409-4888-50 | |
| Naltrexone hydrochloride | Sigma Aldrich | N3136-1G | |
| 23 G BD PrecisionGlide Needles | BD | 305145 | |
| Minivette POCT 50 µl, K3 EDTA | Sarstedt | 17.2113.150 | For capillary blood collection |
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Citazione di questo articolo
Augier, E., Dulman, R. S., Singley, E., Heilig, M. A Method for Evaluating the Reinforcing Properties of Ethanol in Rats without Water Deprivation, Saccharin Fading or Extended Access Training. J. Vis. Exp. (119), e53305, doi:10.3791/53305 (2017).