社会应激对棕色田鼠母性行为和脑内5-HT系统的影响及其关系

社会应激对人和动物的行为和神经内分泌系统会带来强烈影响，而目前社会应激的神经内分泌机制仅在雄性开展了深入研究，由于社会应激模型存在性别差异，所以孕期发生社会应激对母性行为的影响以及产后抑郁之间的关系还不清楚。五羟色胺是介导母性行为的重要神经递质之一，同时发现焦虑抑郁患者五羟色胺也存在异常。本研究拟利用高社会性的棕色田鼠为研究对象，建立孕期社会应激模型，通过母性行为的行为特征分析，再通过双重荧光免疫组化、实时定量PCR、western blot、选择性化学遗传学操控等多种手段从不同层面，阐述五羟色胺及其受体在社会应激的母性行为及产后情绪的影响及调节机制。通过该研究有望回答有关社会应激影响母性行为的生理生态学科学问题，还可以改进动物管理策略、减少社会应激、提高动物福利提供重要的理论依据，并可为保护成年女性产后精神健康提供新思路。

Social defeat occurs when an individual loses in an aggressive encounter, which robustly induces behavioral phenotypes related to anxiety and depression in naturalistic states. Almost all neuroscience studies using social defeat stress have used male rodents because adapting this protocol for females is challenging. It has been known that depression and anxiety are more prevalent in women than men for over 2 decades. The previous iteration of this grant determines that serotonin 5-HT2A and 5-HT2C receptors play distinctive roles in the regulation of rat maternal behavior. Activation of 5-HT2A or 5-HT2C receptors disrupts various maternal responses (e.g. pup retrieval, pup licking, nest building), while blockade of these receptors has no effect. Behaviorally, 5-HT2A and 5-HT2C affect maternal behavior through different behavioral mechanisms. Activation of 5-HT2C suppresses the motivated responses towards pups, while activation of 5-HT2A has little effect on maternal motivation. However, little is known about effect of social defeat on maternal behavior and interaction between social defeat in pregnancy and post-partum depression. The neural basis of 5-HT2C’s maternal effect, which is likely to involve the VTA projecting dopamine (DA) neurons and other non-DA neurons that express 5-HT2C.Here we establish Mandarin voles with higher sociability, suffering vicarious social defeat stress in pregnancy as model to examine maternal behavior, to analyze of maternal affect (e.g., pup preference), maternal motivation (e.g., pup retrieval on an elevated plus maze [EPM]), then to dissect the precise 5-HT2A and 5-HT2C functional neurocircuits underlying maternal behavior and post-partum depression with behavioral technology, double fluorescence immunohistochemistry, RT-PCR, Western-blot and designer receptors exclusively activated by designer drugs(DREADDs) technology. This study will enhance our understanding of the serotonergic neural mechanisms underlying maternal behavior and has implication for postpartum depression, and also provide a new insight to protect the health and well-being of mothers of human and wild animals.