Atcha Zeenat, Rourke Claire, Neo Aveline Hp, Goh Catherine Wh, Lim Jean Sk, Aw Chiu-Cheong, Browne Edward R, Pemberton Darrel J
Centre for Cognition and Neurodegeneration, GlaxoSmithKline R&D China, Singapore.
J Am Assoc Lab Anim Sci. 2010 May;49(3):335-43.
Oral administration of drugs to laboratory rodents typically is achieved by using the gavage technique. Although highly effective, this method occasionally can cause esophageal injury as well as restraint-associated distress, particularly with repeated use. The aim of this study was to assess an alternative oral dosing method that could reduce the distress and morbidity associated with standard gavage techniques. The palatability and pharmacokinetic profile of 2 medicines approved for the treatment of Alzheimer disease, donepezil and galantamine, were investigated in male Lister hooded rats by using a syringe-feeding method and compared with results from traditional gavage administration. In addition, the stimulant nicotine was tested by using the syringe-feeding method in a separate series of experiments. Animals reliably learned to drink voluntarily from the syringe, and latency to drink decreased rapidly. The addition of donepezil, galantamine, or nicotine to sucrose had no apparent effect on the palatability of the solution, although nicotine produced aversive effects that inhibited subsequent voluntary intake. Oral bioavailability was improved by using syringe feeding with donepezil but not galantamine. Both drugs improved cognitive performance in the novel object recognition test, with similar behavioral profiles between the 2 methods of administration. Our results suggest that the syringe-feeding technique is an effective alternative oral dosing method in rats.
给实验用啮齿动物口服给药通常采用灌胃技术。尽管这种方法非常有效，但偶尔会导致食管损伤以及与限制相关的应激反应，尤其是反复使用时。本研究的目的是评估一种替代口服给药方法，该方法可减少与标准灌胃技术相关的应激和发病率。通过使用注射器喂食法，在雄性利斯特戴帽大鼠中研究了两种批准用于治疗阿尔茨海默病的药物多奈哌齐和加兰他敏的适口性和药代动力学特征，并与传统灌胃给药的结果进行了比较。此外，在另一系列实验中，通过使用注射器喂食法对刺激性药物尼古丁进行了测试。动物可靠地学会了自愿从注射器中饮水，饮水潜伏期迅速缩短。在蔗糖中添加多奈哌齐、加兰他敏或尼古丁对溶液的适口性没有明显影响，尽管尼古丁产生了厌恶效应，抑制了随后的自愿摄入。使用注射器喂食多奈哌齐可提高口服生物利用度，但加兰他敏则不然。两种药物在新颖物体识别测试中均改善了认知表现，两种给药方法之间具有相似的行为特征。我们的结果表明，注射器喂食技术是大鼠一种有效的替代口服给药方法。
