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

Self-Administration of Drugs in Mouse Models of Feeding and Obesity.
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在喂食和肥胖的小鼠模型中,药物的自我给药。

DOI:
10.3791/62775
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发表时间:
2021-06-08
期刊:
Journal of visualized experiments : JoVE
影响因子:
--
通讯作者:
Osborn O
Osborn O
中科院分区:
其他
文献类型:
--
作者:
Zapata RC;Zhang D;Chaudry B;Osborn O

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在小鼠身上进行的临床前研究通常依赖于侵入性方案,如注射或口服灌胃,来给药。这些应激给药途径对包括食物摄入和体重在内的重要代谢参数有显著影响。虽然规避这一问题的一个有吸引力的选择是在啮齿动物的食物中合成药物或将其溶解在水中,但这些方法也有局限性,因为它们受到药物在室温下长时间稳定性的影响,药物在水中的溶解度,以及剂量高度依赖于食物或水摄入的时间。药物的持续可用性也限制了如何给药给病人的翻译相关性。为了克服这些限制,药物可以与美味的食物混合,比如花生酱,让老鼠自己服用化合物。小鼠在短时间内可靠且可重复地消耗药物/花生酱颗粒。与注射或灌胃相比,这种方法有利于以最小的压力给药。该方案演示了药物制备、动物适应安慰剂传递和药物传递的方法。这种方法的含义在与药物给药时间和昼夜节律相关的研究中进行了讨论。
Preclinical studies in mice often rely on invasive protocols, such as injections or oral gavage, to deliver drugs. These stressful routes of administration have significant effects on important metabolic parameters including food intake and body weight. Although an attractive option to circumvent this is to compound the drug in rodent food or dissolve it in water, these approaches also have limitations as they are affected by drug stability at room temperature for extended periods of time, the drug’s solubility in water, and that the dosing is highly dependent on timing of food or water intake. The constant availability of the drug also limits translational relevance on how drugs are administered to patients. To overcome these limitations, drugs can be mixed with highly palatable food, such as peanut butter, allowing mice to self-administer compounds. Mice reliably and reproducibly consume the drug/peanut butter pellet in a short time frame. This approach facilitates a delivery approach with minimal stress compared with an injection or gavage. This protocol demonstrates the approach of drug preparation, animal acclimatization to placebo delivery, and drug delivery. The implications of this approach are discussed in studies related to timing of drug administration and the circadian rhythm.
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