Name: self-administration of drugs in mouse models of feeding and obesity
Uploaded: 2021-06-08T15:00:00
Description: Watch this Scientific Journal Video about Self-Administration of Drugs in Mouse Models of Feeding and Obesity at JoVE.com

这项工作得到了国家卫生研究院授予二OO七八七二年R01DK117872和RCZ的拉里L希尔布洛姆基金会奖学金的支持。

所有涉及动物主题的程序都已获得加州大学圣地亚哥分校机构动物护理和使用委员会 （IACUC） 的批准。
1. 制作药物花生酱颗粒
<ol><li>计算在花生酱颗粒中制造所需剂量药物所需的药物量，并缩放到实验所需的批次大小。重要的是，颗粒可以保持在-80°C，这取决于药物的稳定性。</li>
	<li>使用迫击炮和害虫将药物片剂粉碎。</li>
	<li>将花生酱放在拖拉秤上的称重船上，称量计?...

<ol>
	<li>de Meijer, V. E., Le, H. D., Meisel, J. A., Puder, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Repetitive+orogastric+gavage+affects+the+phenotype+of+diet-induced+obese+mice.">Repetitive orogastric gavage affects the phenotype of diet-induced obese mice.</a> Physiology and Behavior. 100 (4), 387-393 (2010).</li><li>Perez-Gomez, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+phenotypic+Caenorhabditis+elegans+screen+identifies+a+selective+suppressor+of+antipsychotic-induced+hyperphagia.">A phenotypic Caenorhabditis elegans screen identifies a selective suppressor of antipsychotic-induced hyperphagia.</a> Nature Communications. 9 (1), 5272 (2018).</li><li>Corbett, A., McGowin, A., Sieber, S., Flannery, T., Sibbitt, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+method+for+reliable+voluntary+oral+administration+of+a+fixed+dosage+(mg/kg)+of+chronic+daily+medication+to+rats.">A method for reliable voluntary oral administration of a fixed dosage (mg/kg) of chronic daily medication to rats.</a> Laboratory Animal. 46 (4), 318-324 (2012).</li><li>Teixeira-Santos, L., Albino-Teixeira, A., Pinho, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+alternative+method+for+oral+drug+administration+by+voluntary+intake+in+male+and+female+mice.">An alternative method for oral drug administration by voluntary intake in male and female mice.</a> Laboratory Animal. 55 (1), 76-80 (2021).</li><li>Zhang, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Method+for+voluntary+oral+administration+of+drugs+in+mice.">Method for voluntary oral administration of drugs in mice.</a> STAR Protocols. 2 (1), 100330 (2021).</li><li>Cope, M. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Risperidone+alters+food+intake,+core+body+temperature,+and+locomotor+activity+in+mice.">Risperidone alters food intake, core body temperature, and locomotor activity in mice.</a> Physiology and Behaviour. 96 (3), 457-463 (2009).</li><li>Barton, B. B., Segger, F., Fischer, K., Obermeier, M., Musil, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Update+on+weight-gain+caused+by+antipsychotics:+a+systematic+review+and+meta-analysis.">Update on weight-gain caused by antipsychotics: a systematic review and meta-analysis.</a> Expert Opinion in Drug Safety. 19 (3), 295-314 (2020).</li><li>Cope, M. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Antipsychotic+drug-induced+weight+gain:+development+of+an+animal+model.">Antipsychotic drug-induced weight gain: development of an animal model.</a> International Journal of Obesity. 29 (6), 607-614 (2005).</li><li>Domecq, J. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+review:+Drugs+commonly+associated+with+weight+change:+a+systematic+review+and+meta-analysis.">Clinical review: Drugs commonly associated with weight change: a systematic review and meta-analysis.</a> Journal of Clinical Endocrinology and Metabolism. 100 (2), 363-370 (2015).</li><li>Wei, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dopamine+D2+receptor+signaling+modulates+pancreatic+beta+cell+circadian+rhythms.">Dopamine D2 receptor signaling modulates pancreatic beta cell circadian rhythms.</a> Psychoneuroendocrinology. 113, 104551 (2020).</li></ol>

在执行此协议时，必须与食物摄入量和体重测量的准确性以及整个研究中药物管理的时间一致。虽然这种自我管理方法需要一个重要的训练阶段，但这对于使小鼠适应花生酱的新颖性，并确保小鼠在给定的时间使用药物尤为重要。一旦建立，它也提供了很大的实验灵活性，可以修改和调整，以提供药物在每天多次在各种剂量。当小鼠以正常食物作为主要营养来源时，这种技术效果最好。当小鼠被?...

这种方法的目标是通过非侵入性、压力最小的程序在小鼠体内提供药物。小鼠的临床前研究通常依赖于压力大、侵入性的药物施用途径，这些途径可能对代谢参数产生重大影响。例如，重复的每日口腔咽伤可以显著减少热量摄入和体重增加的小鼠1。此外，口腔咽伤在技术上可能具有挑战性，并有可能造成伤害。作为替代，老鼠可以自我管理化合物，混合在他们的食物或溶解在他们的饮用水2。然而，这种方法有一个主要的限制，即它依赖于食物或水摄入的自然昼夜时间。此外，药物稳定性或水中的溶质可能是长期以这种方式输送时的主要问题。为了克服这些限制，药物可以与高可口的食物混合，如饼干面团3，果冻4，5或花生酱6，以鼓励在指定的时间在老鼠自我管理。与注射或每日加法1相比，这种方法具有促进药物输送和最小压力的优点。这个程序可以适应，为小鼠提供各种各样的药物。本议定书演示了药物制备、培训以及在高度可口的食物中运送药物的过程。例如，该方法用于向C57BL/6J雌性小鼠施用抗精神病药物利佩里酮。里斯佩里酮是众所周知的有强大的超噬菌体和体重增加效果的患者7，这是很好的模型在啮齿动物6，8。这种管理系统促进一个高度转化的模型，可用于研究各种各样的药物及其对调节食物摄入量和体重的途径的影响9。

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>C57B6/J mice</td>
			<td>Jackson Labs, Sacramento, CA, USA</td>
			<td>664</td>
			<td></td>
		</tr>
		<tr>
			<td>corticosterone pellet mold</td>
			<td>Ted Pella Inc, Redding, CA, USA</td>
			<td>106A</td>
			<td></td>
		</tr>
		<tr>
			<td>Mouse igloo</td>
			<td>VWR, Visalia, CA, USA</td>
			<td>89067-850</td>
			<td>cage enrichment</td>
		</tr>
		<tr>
			<td>peanut butter</td>
			<td>Jif Peanut Butter, Orrville, OH, USA</td>
			<td></td>
			<td>Creamy peanut butter</td>
		</tr>
		<tr>
			<td>pestle and mortar</td>
			<td>VWR, Visalia, CA, USA</td>
			<td>470148-960</td>
			<td></td>
		</tr>
		<tr>
			<td>risperidone</td>
			<td>Patriot Pharmaceuticals, Horsham, PA, USA</td>
			<td>50458-593-50</td>
			<td></td>
		</tr>
		<tr>
			<td>rodent chow</td>
			<td>LabDiet, St. Louis, MO, USA</td>
			<td>5001</td>
			<td></td>
		</tr>
		<tr>
			<td>weigh boat</td>
			<td>VWR, Visalia, CA, USA</td>
			<td>10803-148</td>
			<td></td>
		</tr>
		<tr>
			<td>weighing scale</td>
			<td>Mettler Toledo, Greifensee, Switzerland</td>
			<td>MS104TS</td>
			<td></td>
		</tr>
		<tr>
			<td>Wypall paper X60</td>
			<td>Kimberly-Clark, Corinth, MS, USA</td>
			<td>34865-05</td>
			<td>absorbent paper bedding</td>
		</tr>
	</tbody>
</table>

self-administration of drugs in mouse models of feeding and obesity

小鼠的临床前研究通常依靠侵入性协议，如注射或口服咽部，来提供药物。这些紧张的管理途径对重要的代谢参数有显著的影响，包括食物摄入量和体重。虽然一个有吸引力的选择来规避这是复合药物在啮齿动物的食物或溶解在水中，这些方法也有限制，因为他们受到药物稳定性在室温下很长一段时间，药物在水中的溶解性，剂量是非常依赖于食物或水摄入的时间。药物的不断供应也限制了药物如何给患者施用的转化相关性。为了克服这些限制，药物可以与高度可口的食物混合，如花生酱，允许小鼠自我管理化合物。老鼠可靠和可重复地在短时间内消耗药物/花生酱颗粒。与注射或加法相比，这种方法有助于采用压力最小的分娩方法。该协议演示了药物制备、动物适应安慰剂输送和药物输送的方法。与药物管理时间和昼夜节律有关的研究讨论了这种方法的影响。

在这里介绍的例子中，花生酱用于每天向老鼠提供14天的里佩里酮。
这项研究显示，通过这种方法长期输送利尿酮有助于食物摄入量和体重与控制相比高度可重复增加（图1a，b）。此外，与替代的、压力更大的分娩方法（图1c，d）相比，这种分娩方法可产生高度一致的数据。
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Watch this Scientific Journal Video about Self-Administration of Drugs in Mouse Models of Feeding and Obesity at JoVE.com

Self-Administration of Drugs in Mouse Models of Feeding and Obesity

这个程序的总体目标是描述一种药物的自我管理方法，可用于喂养和肥胖的老鼠模型。

喂养和肥胖小鼠模型中的药物自我管理

Preclinical studies in mice often rely on invasive protocols, such as injections or oral gavage, to deliver drugs. These stressful routes of ...

小鼠的临床前研究通常依赖于侵入性药物的输送，如注射或口服咽部，这些药物会对食物摄入量和体重产生重大影响。为了克服这些限制，药物可以与花生酱等高度可口的食物混合，使小鼠能够与注射或咽动相比，以最小的压力自行管理化合物。首先，使用害虫将药物片剂粉碎在砂浆中。在拖拉秤上称量称重船上计算的花生酱量。然后，将其融化在温水烧杯上，并将计算的粉碎药物量混合到融化的黄油中。冷却后，将花生酱药物混合成霉菌。以类似的方式单独用花生酱准备安慰剂颗粒。将霉菌冷冻在80摄氏度，让花生酱硬化，直到使用。准备标准鼠笼，内衬高度吸水的纸床上用品和浓缩物，包括纸巾和住房圆顶。每个笼子里放一只老鼠。在笼子里提供小食和水，让老鼠适应房屋大约三天。在开始训练之前，让老鼠禁食24小时。第二天，将安慰剂花生酱颗粒放在离底座约1.5英寸的笼子壁上。由于新奇，小鼠在试验的第一天食用花生酱颗粒可能需要大约一个小时。与对照组相比，在花生酱中长期产下利佩里酮14天有助于显著提高每日食物摄入量，并增加C57黑6只雌性小鼠的体重。与花生酱的自产相比，同一剂量的利佩里酮的腹内分娩对食物摄入量或体重增加没有如此强健的影响。在执行此协议时，必须与整个研究中食物摄入量、体重和药物管理时间的测量精度保持一致。这项技术的未来应用包括研究在昼夜节律和代谢健康的背景下，药物输送的时间对食物摄入量和体重增加。

Research

JoVE Journal

Medicine

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice

在自觉的，奔放的小鼠正常血糖高胰岛素 - 夹钳

Type 2 diabetes is characterized by a defect in insulin action. The hyperinsulinemic-euglycemic clamp, or insulin clamp, is widely considered the "gold ...

科研

医学

Segmentation and Measurement of Fat Volumes in Murine Obesity Models Using X-ray Computed Tomography

利用X射线计算机断层扫描在小鼠肥胖模型的FAT卷的分割和测量

Obesity is associated with increased morbidity and mortality as well as reduced metrics in quality of life.1 Both environmental and genetic factors are ...

Live Imaging of Drug Responses in the Tumor Microenvironment in Mouse Models of Breast Cancer

实时成像在乳腺癌小鼠模型中的肿瘤微环境对药物的反应

The tumor microenvironment plays a pivotal role in tumor initiation, progression, metastasis, and the response to anti-cancer therapies. Three-dimensional ...

Mouse Models for Graft Arteriosclerosis

嫁接动脉硬化的小鼠模型

Graft arteriosclerois (GA),  also called allograft vasculopathy, is a pathologic lesion that develops over  months to years in transplanted organs ...

MRI and PET in Mouse Models of Myocardial Infarction

MRI和PET心肌梗死小鼠模型

Myocardial infarction is one of the leading causes of death in the Western world. The similarity of the mouse heart to the human heart has made it an ...

Mouse Kidney Transplantation: Models of Allograft Rejection

鼠肾移植：移植排斥反应模型

Rejection of the transplanted kidney in humans is still a major cause of morbidity and mortality. The mouse model of renal transplantation closely ...

High-frequency Ultrasound Imaging of Mouse Cervical Lymph Nodes

鼠标颈淋巴结高频超声成像

High-frequency ultrasound (HFUS) is widely employed as a non-invasive method for imaging internal anatomic structures in experimental small animal ...

Evaluation of Lung Metastasis in Mouse Mammary Tumor Models by Quantitative Real-time PCR

评价肺转移的小鼠乳腺肿瘤模型定量实时荧光定量PCR

Metastatic disease is the spread of malignant tumor cells from the primary cancer site to a distant organ and is the primary cause of cancer associated ...

Assessing Specificity of Anticancer Drugs In Vitro

Assessing Specificity of Anticancer Drugs In Vitro

评估抗癌药物的特异性<em&gt;体外</em

A procedure for assessing specificity of anticancer drugs in vitro using cultures containing both tumor and non-tumor cells is demonstrated. The key ...

Novel Approach for Simultaneous Recording of Renal Sympathetic Nerve Activity and Blood Pressure with Intravenous Infusion in Conscious, Unrestrained Mice.

清醒、无拘无束的小鼠静脉输液同时记录肾交感神经活动和血压的新方法。

Renal sympathetic nerves contribute significantly to both physiological and pathophysiological phenomena. Evaluating renal sympathetic nerve activity ...