Hou Wenjuan, Huang Shuying, Li Lu, Guo Xing, He Zhixiong, Shang Shufeng, Jia Ziyan, Zhang Lizi, Qu Yishan, Huang Caihong, Li Yin, Li Yitong, Lv Zijian, Tai Fadao
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; College of Bioscience and Engineering, Shaanxi University of Technology, Hanzhong, 723000, China.
Neuropharmacology. 2023 Jun 1;230:109482. doi: 10.1016/j.neuropharm.2023.109482. Epub 2023 Mar 7.
Chronic social stress can cause psychological disease. Although oxytocin (OT) has been showed to modulate effects of chronic social defeat stress (CSDS) on emotional and social behaviors, however, how OT circuits mediate effects of CSDS on emotional and social abnormalities remains unclear. Here, we found that repeated intraperitoneal OT administration in the process of CSDS buffered adverse effects of CSDS on emotional and social behaviors in mandarin voles (Microtus mandarinus) of both sexes except no effect on depression-like behavior of males. Repeated OT treatments during CSDS prevented decrease of oxytocin receptors in nucleus accumbens (NAc) in females, but produced no effects on males. Furthermore, using designer receptors exclusively activated by designer drugs (DREADDs)-based chemogenetic tools, we determined that the activation of the paraventricular nucleus (PVN)-the shell of NAc (NAcs) projections before social defeat during CSDS process significantly prevented the increase of the anxiety-like behaviors and social avoidance induced by CSDS in both sexes, and reversed the depressive-like behaviors induced by CSDS only in females. Besides, optogenetic activation of PVN-NAcs projections after CSDS reduced anxiety-like behaviors and increased levels of sociality. Collectively, we suggest that PVN-NAcs projections modulate emotional and social behaviors during or after the process of CSDS sex-specifically, although AAV viruses did not specifically infect OT neurons. These findings offer potential targets for preventing or treating emotional and social disorders induced by chronic stress.
慢性社会应激会导致心理疾病。尽管催产素（OT）已被证明可调节慢性社会挫败应激（CSDS）对情绪和社会行为的影响，然而，OT神经回路如何介导CSDS对情绪和社会异常的影响仍不清楚。在此，我们发现，在CSDS过程中反复腹腔注射OT可缓冲CSDS对两性中华田鼠（Microtus mandarinus）情绪和社会行为的不利影响，但对雄性的抑郁样行为无影响。在CSDS期间反复进行OT治疗可防止雌性伏隔核（NAc）中催产素受体减少，但对雄性无影响。此外，使用基于设计药物特异性激活的设计受体（DREADDs）的化学遗传学工具，我们确定在CSDS过程中社会挫败前激活室旁核（PVN）-NAc壳（NAcs）投射可显著防止CSDS诱导的两性焦虑样行为和社会回避增加，并仅在雌性中逆转CSDS诱导的抑郁样行为。此外，CSDS后对PVN-NAcs投射进行光遗传学激活可减少焦虑样行为并提高社交水平。总体而言，我们认为PVN-NAcs投射在CSDS过程中或之后对情绪和社会行为具有性别特异性调节作用，尽管腺相关病毒并未特异性感染OT神经元。这些发现为预防或治疗慢性应激诱导的情绪和社会障碍提供了潜在靶点。
