A single prolonged stress paradigm produces enduring impairments in social bonding in monogamous prairie voles.
A single prolonged stress paradigm produces enduring impairments in social bonding in monogamous prairie voles.
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DOI：
10.1016/j.bbr.2016.08.022
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发表时间：
2016-12-15
影响因子：
2.7
通讯作者：
Mitsui S
中科院分区：
文献类型：
--
作者：
Arai A;Hirota Y;Miyase N;Miyata S;Young LJ;Osako Y;Yuri K;Mitsui S
自然灾害、暴力犯罪、悲惨事故和战争等创伤性事件可能会对包括婚姻关系在内的社会关系产生破坏性影响。我们发展了一种单一的延长应激(SPS)范式，包括束缚、强迫游泳和乙醚麻醉，以建立与创伤后应激障碍相关的动物模型。我们将SPS范式应用于一夫一妻制啮齿动物草原田鼠(Microtus Ochrogaster)，以确定创伤事件是否影响配对纽带的建立。我们没有检测到SPS治疗对非享乐性或焦虑样行为的影响。经过6天的同居后，经过假处理的雄性田鼠与伴侣雌性田鼠挤在一起，持续的时间比与新出现的雌性田鼠更长，这表明它们之间存在着一种结对的纽带。相比之下，接受SPS处理的田鼠不分青红皂白地与新奇的雌性田鼠和伴侣雌性田鼠挤在一起。有趣的是，在SPS治疗后，口服帕罗西汀(一种选择性5-羟色胺再摄取抑制剂(SSRI))可以挽救配对结合的损害。免疫组织化学分析显示，SPS治疗后7d，视上核(SON)催产素免疫反应(IR)显著降低，而室旁核(PVN)则无明显变化，SPS治疗后14d恢复正常。在出现雌性伴侣后，与假手术组相比，经SPS处理的田鼠的Fos-IR标记的催产素神经元显著增加，而与帕罗西汀给药无关。我们的结果表明，创伤事件可能通过与5-羟色胺能系统的相互作用扰乱对键的形成，SSRIs是治疗创伤事件引起的社会问题的候选药物。此外，田鼠SPS模型可能有助于理解创伤事件损害社会纽带的潜在机制。
Traumatic events such as natural disasters, violent crimes, tragic accidents, and war, can have devastating impacts on social relationships, including marital partnerships. We developed a single prolonged stress (SPS) paradigm, which consisted of restraint, forced swimming, and ether anesthesia, to establish an animal model relevant to post-traumatic stress disorder. We applied a SPS paradigm to a monogamous rodent, the prairie vole (Microtus ochrogaster) in order to determine whether a traumatic event affects the establishment of pair bonds. We did not detect effects of the SPS treatment on anhedonic or anxiety-like behavior. Sham-treated male voles huddled with their partner females, following a 6 day cohabitation, for a longer duration than with a novel female, indicative of a pair bond. In contrast, SPS-treated voles indiscriminately huddled with the novel and partner females. Interestingly, the impairment of pair bonding was rescued by oral administration of paroxetine, a selective serotonin reuptake inhibitor (SSRI), after the SPS treatment. Immunohistochemical analyses revealed that oxytocin immunoreactivity (IR) was significantly decreased in the supraoptic nucleus (SON), but not in the paraventricular nucleus (PVN), 7 days after SPS treatment, and recovered 14 days after SPS treatment. After the presentation of a partner female, oxytocin neurons labeled with Fos IR was significantly increased in SPS-treated voles compared with sham-treated voles regardless of paroxetine administration. Our results suggest that traumatic events disturb the formation of pair bond possibly through an interaction with the serotonergic system, and that SSRIs are candidates for the treatment of social problems caused by traumatic events. Further, a vole SPS model may be useful for understanding mechanisms underlying the impairment of social bonding by traumatic events.