The effects of tamoxifen on mouse behavior

• Published in: Genes, brain and behavior brain and behavior, 2020-04, Vol.19 (4), p.e12620-n/a
• Main Authors: Li, Xin, Du, Zhuo‐Jun, Chen, Man‐Qi, Chen, Jia‐Jun, Liang, Zhi‐Man, Ding, Xiao‐Ting, Zhou, Min, Li, Shu‐Ji, Li, Xiao‐Wen, Yang, Jian‐Ming, Gao, Tian‐Ming
• Format: Article
• Language: English
• Subjects: Acute effects; Animal models; Animals; Anxiety; Anxiety - etiology; behavior; Chronic effects; Cre recombinase; depression; Gene Targeting - methods; Gene Targeting - standards; Helplessness, Learned; inducible mutagenesis; Learned helplessness; Locomotion - drug effects; Locomotor activity; Male; Maze Learning - drug effects; Mice; Mice, Inbred C57BL; Mutagenesis; psychiatry; Receptors, Estrogen - antagonists & inhibitors; Social Behavior; Social interactions; Tamoxifen; Tamoxifen - adverse effects; Tamoxifen - pharmacology
• ISSN: 1601-1848; 1601-183X
• DOI: 10.1111/gbb.12620

The CreERT2 recombinase system is an advanced method to temporally control site‐specific mutagenesis in adult rodents. In this process, tamoxifen is injected to induce Cre recombinase expression, and then, Cre recombinase can excise LoxP‐flanked DNA. However, tamoxifen is a nonselective estrogen receptor antagonist that may influence behavioral alterations. Therefore, we designed five different protocols (acute effects, chronic effects, chronic effects after social defeat model, chronic effects after learned helplessness model, chronic effects after isolation models) to explore whether tamoxifen affects mouse behavior. Researching the acute/chronic effects of tamoxifen, we found that tamoxifen could influence locomotor activity, anxiety and immobility time in the forced swimming test. Researching the chronic effects of tamoxifen after social defeat/learned helplessness/isolation models, we found that tamoxifen could also influence locomotor activity, social interaction and anxiety. Therefore, the effects of tamoxifen are more complex than previously reported. Our results show, for the first time, that tamoxifen affects behavior in mouse models. Meanwhile, we compare the effects of tamoxifen in different protocols. These results will provide important information when designing similar experiments. First, in gene editing research, tamoxifen is injected to induce Cre expression in the CreERT2 recombinase system. Tamoxifen is a nonselective estrogen receptor antagonist. We find the effects of tamoxifen are more complex than previously reported. The effects of mutagenesis might be concealed by the effects of tamoxifen in many behavior tests. Second, our results show, for the first time, that tamoxifen affects behavior in mouse models and we compare the effects of tamoxifen in different protocols. These results will provide important information when designing similar experiments.