Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, China.
Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an 710062, China.
Prog Neuropsychopharmacol Biol Psychiatry. 2019 Dec 20;95:109704. doi: 10.1016/j.pnpbp.2019.109704. Epub 2019 Jul 19.
Chronic social defeat stress (CSDS) exacerbated the development of stress-related psychiatric disorders, and the social recognition dysfunction is the core feature of many psychiatric disorders. However, the effects of CSDS on female social recognition and the underlying neural mechanisms remain unclear. Using highly aggressive adult female mandarin voles (Microtus mandarinus) as animal model, the aim of this work is to investigate the effects of CSDS on social recognition in adult female rodents and the neurobiological mechanisms underlying these effects. Our results indicate the CSDS disrupted the normal social recognition in adult female voles. Meanwhile, defeated voles exhibited increased neural activity in the DG, CA1 and CA3 of the hippocampus. Furthermore, CSDS reduced levels of serotonin (5-HT) and serotonin 1A receptors (5-HTR) in the CA3. We also discovered that microinjection of 8-OH-DPAT into the CA3 effectively reversed the social recognition deficits induced by CSDS, and an infusion of WAY-100635 into the CA3 of control female voles impaired social recognition. Moreover, targeted activation of the 5-HT neuron projection from the DRN to CA3 by long-term administration of CNO significantly prevented the CSDS induced social recognition deficits. Taken together, our study demonstrated that CSDS induced social recognition deficits in adult female voles, and these effects were mediated by the action of 5-HT on the 5-HTR in the hippocampus CA3. The projection from the DRN to CA3 may be involved in social recognition deficits induced by CSDS.
慢性社会挫败应激（CSDS）加剧了与应激相关的精神障碍的发展，而社会认知功能障碍是许多精神障碍的核心特征。然而，CSDS 对女性社会认知的影响及其潜在的神经机制仍不清楚。本研究使用具有高攻击性的成年雌性蒙古沙鼠（Microtus mandarinus）作为动物模型，旨在探讨 CSDS 对成年雌性啮齿动物社会认知的影响及其潜在的神经生物学机制。我们的结果表明，CSDS 破坏了成年雌性沙鼠的正常社会认知。同时，被击败的沙鼠在海马的 DG、CA1 和 CA3 区表现出增加的神经活动。此外，CSDS 降低了 CA3 中的 5-羟色胺（5-HT）和 5-羟色胺 1A 受体（5-HTR）水平。我们还发现，在 CA3 中微注射 8-OH-DPAT 可有效逆转 CSDS 引起的社会认知缺陷，而在对照组雌性沙鼠的 CA3 中输注 WAY-100635 则损害了社会认知。此外，通过长期给予 CNO 靶向激活 DRN 到 CA3 的 5-HT 神经元投射，显著防止了 CSDS 引起的社会认知缺陷。综上所述，本研究表明 CSDS 导致成年雌性沙鼠出现社会认知缺陷，而这些效应是通过海马 CA3 中的 5-HT 对 5-HTR 的作用介导的。DRN 到 CA3 的投射可能参与了 CSDS 引起的社会认知缺陷。
