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
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DOI：
10.1258/la.2012.012018
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发表时间：
2012-10-01
影响因子：
2.4
通讯作者：
Sibbitt, Bethany
中科院分区：
文献类型：
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作者：
Corbett, Adrian;McGowin, Audrey;Sibbitt, Bethany
压力可以影响许多生理过程，包括成人神经发生、新陈代谢、心血管功能、免疫功能、神经生理功能、内分泌功能和损伤后的炎症过程。在测试可用于治疗各种疾病或损伤的药物时，减少与动物模型慢性给药相关的压力应该是当务之急，这促使我们设计了一种可靠的自愿口服给药方法。使用我们的自愿口服给药系统，在四种不同的大鼠种群或品系（Wistar、Fisher、Long Evans 和 Sprague Dawley）中对各种药物组合与载体对照进行了测试。将口服药物放入商店购买的糖曲奇面团球（约4克）中，使干药物与面团充分融合。该方法在四种不同种群或品系的大鼠中始终有效地输送药物（完全摄入），可靠性范围为 98.6% 至 100%。在研究期间的任何时间，每个种群或品系中的老鼠的百分比范围从斯普拉格道利的1%，威斯塔和费舍尔的约4%，到朗埃文斯的约16%。对血清和脑样本进行高效液相色谱 (HPLC) 分析，检测我们服用的药物之一：5 mg/kg 氟西汀。 HPLC 分析表明，摄入后 2-4 小时可检测到血清水平，但摄入后 24 小时则检测不到。然而，在摄入单剂量一周多后，大脑样本显示出可检测到的氟西汀和去甲氟西汀水平，并且在每天服用药物一个月后，去甲氟西汀水平更高。
Stress can influence a number of physiological processes including adult neurogenesis, metabolism, cardiovascular function, immune function, neurophysiological function, endocrine function and inflammatory processes following injury. In testing drugs which may be used to treat various diseases or injuries, reducing stress associated with chronic drug delivery to animal models should then be an imperative, which led us to design a reliable voluntary oral drug delivery method. Various drug combinations were tested versus vehicle controls in four different rat stocks or strains (Wistar, Fisher, Long Evans and Sprague Dawley) with our voluntary oral delivery system. Oral medications were placed into a store-bought sugar cookie dough ball (similar to 4 g), thoroughly integrating the dry drugs with the dough. This method has worked consistently to deliver the medication (complete ingestion) in four different stocks or strains of rats, with reliabilities ranging from 98.6% to 100%. The percentage of rats in each stock or strain that have at any time during the study had incomplete ingestion of the drugs ranged from 1% in Sprague Dawley, approximately 4% in Wistar and Fisher, to approximately 16% in Long Evans. Both serum and brain samples were analysed for high-performance liquid chromatography (HPLC) detection of one of our administered drugs: 5 mg/kg fluoxetine. HPLC analysis shows that serum levels are detectable 2-4 h after ingestion, but not 24 h after ingestion. Brain samples however, showed detectable levels of both fluoxetine and norfluoxetine more than a week following ingestion of a single dose, with higher norfluoxetine levels seen following a month of daily administered drugs.