Refined tamoxifen administration in mice by encouraging voluntary consumption of palatable formulations.

<p>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 <span>tamoxifen</span> <span>or</span> do not <span>allow for</span> precise timing or dosing of the drugs. <span>For more than two decades, tamoxifen has been administered by oral gavage or injection to </span>CreER^T2/loxP gene-modified mouse models<span> </span>to <span>spatiotemporally control gene expression,</span><span> with the numbers of such inducible models </span><span>steadily increasing in recent years. </span>Animal-friendly procedures <span>for</span> accurately administering <span>tamoxifen or </span><span>other water-insoluble </span><span>drugs </span>would, therefore, have an important impact on animal <span>welfare.</span> <span>Based on a previously published micropipette feeding protocol, we developed palatable formulations to encourage voluntary consumption of tamoxifen. We </span><span>evaluated</span><span> </span><span>the acceptance of the new formulations by mice during training and treatment and assessed the efficacy of </span><span>tamoxifen-mediated induction of </span>CreER^T2/loxP-dependent reporter <span>gene</span><span>s</span><span>.</span> <span>Both sweetened </span><span>milk</span><span> and syrup-based formulations encouraged mice to consume tamoxifen voluntarily, but only sweetened milk formulations were statistically </span><span>non-inferior</span><span> to oral </span><span>gavage or intraperitoneal injections in inducing </span><span>CreER^T2-mediated</span><span> gene expression. </span><span><span>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.</span></span> 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.&nbsp;<span>The new palatable solutions encourage voluntary consumption of tamoxifen without loss of </span><span>efficacy</span><span> compared to oral gavage or injections and </span><span>thus represent</span><span> </span>a refined administration method.</p>