Fluoxetine reverses early-life stress-induced depressive-like behaviors and region-specific alterations of monoamine transporters in female mice

氟西汀可逆转雌性小鼠早期生活压力引起的抑郁样行为和单胺转运蛋白的区域特异性改变

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作者:Jia-Ya Zheng, Xue-Xin Li, Xiao Liu, Chen-Chen Zhang, Ya-Xin Sun, Yu-Nu Ma, Hong-Li Wang, Yun-Ai Su, Tian-Mei Si, Ji-Tao Li

Abstract

The sex difference that females are more vulnerable to depression than males has been recently replicated in an animal model of early-life stress (ES) called the limited bedding and nesting material (LBN) paradigm. Adopting this animal model, we have previously examined the effects of ES on monoamine transporter (MATs) expression in stress-related regions in adult female mice, and the reversal effects of a novel multimodal antidepressant, vortioxetine. In this study, replacing vortioxetine with a classical antidepressant, fluoxetine, we aimed to replicate the ES effects in adult female mice and to elucidate the commonality and differences between fluoxetine and vortioxetine. We found that systemic 30-day treatment with fluoxetine successfully reversed ES-induced depression-like behaviors (especially sucrose preference) in adult female mice. At the molecular level, we largely replicated the ES effects, such as reduced serotonin transporter (SERT) expression in the amygdala and increased norepinephrine transporter (NET) expression in the medial prefrontal cortex (mPFC) and hippocampus. Similar reversal effects of fluoxetine and vortioxetine were observed, including SERT in the amygdala and NET in the mPFC, whereas different reversal effects were observed for NET in the hippocampus and vesicular monoamine transporters expression in the nucleus accumbens. Overall, these results demonstrate the validity of the LBN paradigm to induce depression-like behaviors in female mice, highlight the involvement of region-specific MATs in ES-induced depression-like behaviors, and provide insights for further investigation of neurobiological mechanisms, treatment, and prevention associated with depression in women.

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