A less stressful alternative to oral gavage for pharmacological and toxicological studies in mice.
A less stressful alternative to oral gavage for pharmacological and toxicological studies in mice.
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DOI：
10.1016/j.taap.2012.01.025
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发表时间：
2012-04-01
影响因子：
3.8
通讯作者：
Felton, Linda A.
中科院分区：
文献类型：
--
作者：
Walker, Mary K.;Boberg, Jason R.;Walsh, Mary T.;Wolf, Valerie;Trujillo, Alisha;Duke, Melissa Skelton;Palme, Rupert;Felton, Linda A.
口服灌胃给药可引起应激，并可能混淆实验测量，特别是当血压和心率是感兴趣的终点时。因此，我们开发了一种药丸配方，小鼠可以自愿服用，并测试了药丸剂量比口服灌胃的压力要小得多的假设。C57Bl/6雄性小鼠被单独饲养，连续四天暴露于一个人走进房间（第1周，对照组），一个药丸被放入笼子（第2周），一剂水通过口服灌胃（第3周）。治疗后5小时用无线遥测法连续记录血压和心率，治疗后6-10小时收集粪便分析皮质酮代谢物。与对照组相比，药片和灌胃剂量在第一个小时内显著增加了平均动脉压（MAP）。然而，灌胃后MAP的增加明显更大，并在5小时内保持升高，而在服药后2小时内MAP恢复正常。与对照组相比，服药和灌胃在第一个小时内都没有显著增加心率；然而，药片剂量显著降低心率，而灌胃显著增加心率2-5小时后给药。给药24小时后MAP和心率无差异。最后，只有灌胃剂量显著增加粪便皮质酮代谢物，表明通过激活下丘脑-垂体-肾上腺轴的系统性应激反应。这些数据表明，这种给药方法对小鼠的压力明显小于口服灌胃。
Oral gavage dosing can induce stress and potentially confound experimental measurements, particularly when blood pressure and heart rate are endpoints of interest. Thus, we developed a pill formulation that mice would voluntarily consume and tested the hypothesis that pill dosing would be significantly less stressful than oral gavage. C57Bl/6 male mice were singly housed and on four consecutive days were exposed to an individual walking into the room (week 1, control), a pill being placed into the cage (week 2), and a dose of water via oral gavage (week 3). Blood pressure and heart rate were recorded by radiotelemetry continuously for 5 hr after treatment, and feces collected 6–10 hr after treatment for analysis of corticosterone metabolites. Both pill and gavage dosing significantly increased mean arterial pressure (MAP) during the first hour, compared to control. However, the increase in MAP was significantly greater after gavage and remained elevated up to 5 hr, while MAP returned to normal within 2 hr after a pill. Neither pill nor gavage dosing significantly increased heart rate during the first hour, compared to control; however, pill dosing significantly reduced heart rate while gavage significantly increased heart rate 2–5 hr post dosing. MAP and heart rate did not differ 24 hr after dosing. Lastly, only gavage dosing significantly increased fecal corticosterone metabolites, indicating a systemic stress response via activation of the hypothalamic-pituitary-adrenal axis. These data demonstrated that this pill dosing method of mice is significantly less stressful than oral gavage.
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影响因子：
3.3
作者：
Mills, PA;Huetteman, DA;Kramer, K
通讯作者：
Kramer, K
影响因子：
5.8
作者：
Zhang, Nan;Agbor, Larry N.;Scott, Jason A.;Zalobowski, Tyler;Elased, Khalid M.;Trujillo, Alicia;Duke, Melissa Skelton;Wolf, Valerie;Walsh, Mary T.;Born, Jerry L.;Felton, Linda A.;Wang, Jian;Wang, Wei;Kanagy, Nancy L.;Walker, Mary K.
通讯作者：
Walker, Mary K.
高血压，心脏肥大和受损的血管弛豫受到2,3,7,8-四氯迪本佐-P-二恶英的诱导，与超氧化物的增加有关。
影响因子：
3.2
作者：
Kopf, Phillip G.;Huwe, Janice K.;Walker, Mary K.
通讯作者：
Walker, Mary K.
影响因子：
2.7
作者：
Touma, C;Sachser, N;Palme, R
通讯作者：
Palme, R
影响因子：
2.9
作者：
SCHANTZ, SL;BOWMAN, RE
通讯作者：
BOWMAN, RE