College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, China.
Int J Neuropsychopharmacol. 2019 Mar 1;22(3):208-220. doi: 10.1093/ijnp/pyy093.
Most previous studies have focused on the effects of social defeat in male juvenile individuals. Whether chronic social defeat stress in adulthood affects female emotion and the underlying mechanisms remains unclear.
Using highly aggressive adult female mandarin voles (Microtus mandarinus), the present study aimed to determine the effects of chronic social defeat stress on anxiety- and depression-like behaviors in adult female rodents and investigate the neurobiological mechanisms underlying these effects.
Exposure of adult female voles to social defeat stress for 14 days reduced the time spent in the central area of the open field test and in the open arms of the elevated plus maze and lengthened the immobility time in the tail suspension and forced swimming tests, indicating increased anxiety- and depression-like behaviors. Meanwhile, defeated voles exhibited increased neural activity in the prelimbic cortex of the medial prefrontal cortex. Furthermore, chronic social defeat stress reduced serotonin projections and levels of serotonin 1A receptors in the medial prefrontal cortex-prelimbic cortex. Intra-prelimbic cortex microinjections of the serotonin 1A receptor agonist 8-OH-DPAT reversed the alterations in emotional behaviors, whereas injections of the serotonin 1A receptor antagonist WAY-100635 into the prelimbic cortex of control voles increased the levels of anxiety- and depression-like behaviors.
Taken together, our results demonstrated that chronic social defeat stress increased anxiety- and depression-like behaviors in adult female voles, and these effects were mediated by the action of serotonin on the serotonin 1A receptors in the prelimbic cortex. The serotonin system may be a promising target to treat emotional disorders induced by chronic social defeat stress.
大多数先前的研究都集中在雄性幼年个体遭受社会挫败的影响上。成年期慢性社会挫败应激是否会影响女性的情绪及其潜在机制尚不清楚。
本研究使用具有高度攻击性的成年雌性蒙古沙鼠（Microtus mandarinus），旨在确定慢性社会挫败应激对成年雌性啮齿动物焦虑和抑郁样行为的影响，并探讨这些影响的神经生物学机制。
将成年雌性沙鼠暴露于社会挫败应激 14 天，减少了它们在开阔场测试的中央区域和高架十字迷宫的开放臂中的停留时间，延长了它们在尾部悬挂和强迫游泳测试中的不动时间，表明焦虑和抑郁样行为增加。同时，被击败的沙鼠在前扣带回皮层的内侧前额叶皮层中表现出增加的神经活动。此外，慢性社会挫败应激减少了内侧前额叶皮层-前扣带回皮层中的 5-羟色胺投射和 5-羟色胺 1A 受体水平。在前扣带回皮层内微注射 5-羟色胺 1A 受体激动剂 8-OH-DPAT 可逆转情绪行为的改变，而在对照组沙鼠的前扣带回皮层内注射 5-羟色胺 1A 受体拮抗剂 WAY-100635 则增加了焦虑和抑郁样行为的水平。
综上所述，我们的研究结果表明，慢性社会挫败应激增加了成年雌性沙鼠的焦虑和抑郁样行为，这些影响是通过 5-羟色胺在前扣带回皮层上的 5-羟色胺 1A 受体的作用介导的。5-羟色胺系统可能是治疗慢性社会挫败应激引起的情绪障碍的一个有前途的靶点。
