McDonnell-Dowling Kate, Kleefeld Silke, Kelly John P
Discipline of Pharmacology and Therapeutics, School of Medicine, National University of Ireland, Galway, Ireland.
J Am Assoc Lab Anim Sci. 2017 Jan 1;56(1):79-83.
Oral gavage is a popular route of drug administration during preclinical testing. Despite the growing body of information regarding the effects of oral gavage and the stress associated with this technique, the consequences of such exposure during pregnancy or lactation have rarely been investigated. Therefore, we sought to determine the consequences of oral gavage exposure during pregnancy and lactation on the neurodevelopment and behavior of rat offspring. Pregnant Sprague-Dawley dams underwent either no treatment or oral gavage of distilled water once daily from gestational day 7 until postnatal day 21. Oral gavage treatment had no significant effect on maternal parameters, including bodyweight gain, duration of gestation, litter size, and incidence of neonatal death. Compared with their counterparts from untreated dams, male and female progeny of gavaged dams had longer body lengths on PND 7 and 14 but reduced forelimb grip performance on PND 14 and 17. Therefore, the use of oral gavage during pregnancy and lactation in rats can have opposite effects on the somatic and behavioral development of the offspring. These factors should be considered when using oral gavage as a route of administration during pregnancy. In addition, the inclusion of no-treatment controls is important because they may reveal various restraint-associated effects.
灌胃给药是临床前试验中常用的给药途径。尽管关于灌胃给药的影响以及与该技术相关的应激的信息越来越多,但孕期或哺乳期这种暴露的后果却很少被研究。因此,我们试图确定孕期和哺乳期灌胃给药对大鼠后代神经发育和行为的影响。怀孕的斯普拉格-道利母鼠从妊娠第7天到出生后第21天,要么不接受治疗,要么每天一次灌胃蒸馏水。灌胃给药对母体参数没有显著影响,包括体重增加、妊娠期时长、窝仔数和新生儿死亡率。与未接受灌胃的母鼠所产的后代相比,接受灌胃的母鼠所产的雄性和雌性后代在出生后第7天和第14天体长更长,但在出生后第14天和第17天前肢抓握能力下降。因此,大鼠在孕期和哺乳期使用灌胃给药对后代的身体和行为发育可能有相反的影响。在孕期将灌胃作为给药途径时应考虑这些因素。此外,纳入未治疗对照组很重要,因为它们可能揭示各种与限制相关的影响。