Drug administration in preclinical rodent models is essential for research and the development of novel therapies. Compassionate administration methods have been developed, but these are mostly incompatible with water-insoluble drugs such as tamoxifen or do not allow for precise timing or dosing of the drugs. For more than two decades, tamoxifen has been administered by oral gavage or injection to CreER^T2–loxP gene-modified mouse models to spatiotemporally control gene expression, with the numbers of such inducible models steadily increasing in recent years. Animal-friendly procedures for accurately administering tamoxifen or other water-insoluble drugs would, therefore, have an important impact on animal welfare. On the basis of a previously published micropipette feeding protocol, we developed palatable formulations to encourage voluntary consumption of tamoxifen. We evaluated the acceptance of the new formulations by mice during training and treatment and assessed the efficacy of tamoxifen-mediated induction of CreER^T2–loxP-dependent reporter genes. Both sweetened milk and syrup-based formulations encouraged mice to consume tamoxifen voluntarily, but only sweetened milk formulations were statistically noninferior to oral gavage or intraperitoneal injections in inducing CreER^T2-mediated gene expression. Serum concentrations of tamoxifen metabolites, quantified using an in-house-developed cell assay, confirmed the lower efficacy of syrup- as compared to sweetened milk-based formulations. We found dosing with a micropipette to be more accurate than oral gavage or injection, with the added advantage that the method requires little training for the experimenter. The new palatable solutions encourage voluntary consumption of tamoxifen without loss of efficacy compared to oral gavage or injections and thus represent a refined administration method.

临床前啮齿动物模型中的药物给药对于新疗法的研究和开发至关重要。同情性给药方法已经被开发出来，但这些方法大多与不溶于水的药物（例如他莫昔芬）不相容，或者不允许药物的精确计时或剂量。二十多年来，他莫昔芬一直通过口服灌胃或注射的方式给予CreER ^T2 - loxP基因修饰小鼠模型，以时空控制基因表达，近年来此类诱导模型的数量稳步增加。因此，准确施用他莫昔芬或其他水不溶性药物的动物友好型程序将对动物福利产生重要影响。根据之前发布的微量移液器喂养方案，我们开发了可口的配方，以鼓励自愿消费他莫昔芬。我们评估了小鼠在训练和治疗期间对新制剂的接受程度，并评估了他莫昔芬介导的 CreER ^T2 – loxP依赖性报告基因诱导的功效。加糖牛奶和糖浆制剂都鼓励小鼠自愿摄入他莫昔芬，但在诱导 CreER ^T2介导的基因表达方面，只有加糖牛奶制剂在统计学上不劣于口服强饲或腹膜内注射。使用内部开发的细胞测定法对他莫昔芬代谢物的血清浓度进行定量，证实与甜奶配方相比，糖浆的功效较低。我们发现使用微量移液器给药比口服灌胃或注射更准确，其额外优点是该方法不需要对实验者进行培训。 与口服灌胃或注射相比，新的可口解决方案鼓励自愿服用他莫昔芬而不损失疗效，因此代表了一种改进的给药方法。