Tamoxifen exacerbates morbidity and mortality in mice receiving medetomidine anaesthesia

Tamoxifen-induced CreER-LoxP recombination is often used to induce spatiotemporally controlled gene deletion in genetically modified mice. Prior work has shown that tamoxifen and tamoxifen-induced CreER activation can have off-target effects that should be controlled. However, it has not yet been reported whether tamoxifen administration, independently of CreER expression, interacts adversely with commonly used anaesthetic drugs such as medetomidine or its enantiomer dexmedetomidine in mice. Here we report a high incidence of urinary plug formation linked to morbidity after ketamine-medetomidine anaesthesia in male mice previously injected with tamoxifen. As dexmedetomidine causes morbidity and mortality in male mice at higher rates than medetomidine, our findings suggest that both medetomidine and dexmedetomidine are both contra-indicated for male mice after tamoxifen treatment.