State Key Laboratory of Organ Failure Research, Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Collaborative Innovation Center for Brain Science, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Genes Brain Behav. 2020 Apr;19(4):e12620. doi: 10.1111/gbb.12620. Epub 2019 Nov 6.
The CreER 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.
CreER 重组酶系统是一种在成年啮齿动物中进行时空控制的特定部位基因突变的先进方法。在这个过程中，给予他莫昔芬注射以诱导 Cre 重组酶表达，然后 Cre 重组酶可以切除 LoxP 侧翼的 DNA。然而，他莫昔芬是一种非选择性雌激素受体拮抗剂，可能会影响行为改变。因此，我们设计了五种不同的方案（急性作用、慢性作用、慢性作用后社会挫败模型、慢性作用后习得性无助模型、慢性作用后隔离模型）来探索他莫昔芬是否会影响小鼠行为。研究他莫昔芬的急性/慢性作用时，我们发现他莫昔芬可以影响运动活动、焦虑和强迫游泳试验中的不动时间。研究慢性作用后社会挫败/习得性无助/隔离模型，我们发现他莫昔芬也可以影响运动活动、社交互动和焦虑。因此，他莫昔芬的作用比以前报道的更为复杂。我们的结果首次表明他莫昔芬影响小鼠模型中的行为。同时，我们比较了不同方案中他莫昔芬的作用。这些结果将在设计类似实验时提供重要信息。
