Kocovski Pece, Dang Phuc T, D'Souza Claretta S, Stamper Christopher E, Hale Matthew W, Orian Jacqueline M
1 School of Psychology and Public Health, La Trobe University, Australia.
2 Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Australia.
Lab Anim. 2018 Oct;52(5):470-478. doi: 10.1177/0023677218756156. Epub 2018 Feb 14.
Oral gavage is commonly used in pre-clinical drug evaluation, but is potentially aversive and may induce behavioral effects independent of compounds under investigation. This study examined the combined effects of repeated oral gavage and disease induction on anxiety-like behavior in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. The C57BL/6J and NOD/ShiLtJ EAE variants were exposed to sham-EAE induction or untreated control conditions, and either daily oral gavage or home cage conditions. Anxiety-like behavior was subsequently assessed in the elevated plus maze. C57BL/6J mice exhibited increased anxiety-like behavior, relative to NOD/ShiLtJ mice, in response to repeated gavage, whereas sham-EAE induction and repeated gavage were associated with increased anxiety-like behavior in NOD/ShiLtJ mice. Thus, exposure to the induction procedure and repeated gavage differentially altered subsequent anxiety-like behavior in the two EAE variants. Future pre-clinical studies should rely on prior evaluation of parameters of the experimental design using sham-EAE mice. Additionally, less aversive administration routes should be utilized wherever possible to ensure that procedures do not distort effects of the therapeutic under investigation.
灌胃法常用于临床前药物评估，但可能会引起反感，并且可能会诱发与所研究化合物无关的行为效应。本研究在多发性硬化症的实验性自身免疫性脑脊髓炎（EAE）模型中，考察了重复灌胃和疾病诱导对焦虑样行为的联合影响。将C57BL/6J和NOD/ShiLtJ EAE变体暴露于假EAE诱导或未处理的对照条件下，并分别给予每日灌胃或置于饲养笼条件下。随后在高架十字迷宫中评估焦虑样行为。相对于NOD/ShiLtJ小鼠，C57BL/6J小鼠在重复灌胃后表现出焦虑样行为增加，而假EAE诱导和重复灌胃与NOD/ShiLtJ小鼠焦虑样行为增加有关。因此，在两种EAE变体中，暴露于诱导程序和重复灌胃对随后的焦虑样行为有不同的影响。未来的临床前研究应依赖于使用假EAE小鼠对实验设计参数进行预先评估。此外，应尽可能采用较不引起反感的给药途径，以确保实验程序不会扭曲所研究治疗方法的效果。
