Oxytocin receptor antagonist reverses the blunting effect of pair bonding on fear learning in monogamous prairie voles
Oxytocin receptor antagonist reverses the blunting effect of pair bonding on fear learning in monogamous prairie voles
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DOI：
10.1016/j.yhbeh.2020.104685
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发表时间：
2020-04-01
影响因子：
3.5
通讯作者：
Mitsui, Shinichi
中科院分区：
文献类型：
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作者：
Hirota, Yu;Arai, Aki;Mitsui, Shinichi
众所周知，配偶、家庭成员和朋友之间的社会关系会影响身心健康。特别是，社会性伴侣之间的持久联系对认知、社交、情感和身体健康有着深远的影响。我们之前曾报道过，一夫一妻制的草原田鼠（Microtus ochrogaster）的配对会受到单一长期应激（SPS）范式的阻碍，这会导致大鼠出现类似于创伤后应激障碍（PTSD）患者的行为和内分泌症状（Arai et al., 2016）。由于恐惧记忆功能对于创伤后应激障碍 (PTSD) 等焦虑相关疾病至关重要，因此我们研究了配对关系对草原田鼠恐惧学习的影响。我们将 SPS 范式应用于与雄性（笼交组）或雌性（配对组）同居后的雄性草原田鼠。在 SPS 治疗后的情境恐惧条件测试中，笼伴组（而非配对组）表现出增强的恐惧反应。免疫组织化学分析显示，在情境恐惧条件反射测试后，配对组中央杏仁核中的cFos阳性细胞增加，并且配对组下丘脑室旁核中的催产素免疫反应性显着高于笼伴组。被动回避测试（另一种基于恐惧的学习测试）证实了恐惧记忆反应的这种配对依赖性减弱。有趣的是，在被动回避测试前30分钟，脑室内注射催产素受体拮抗剂，可以阻断配对联结对恐惧学习的钝化作用。因此，社会性伴侣之间的配对会在伴侣不在场的情况下产生社交缓冲，从而削弱恐惧学习，这可能是由催产素信号介导的。
Social relationships among spouses, family members, and friends are known to affect physical and mental health. In particular, long-lasting bonds between socio-sexual partners have profound effects on cognitive, social, emotional, and physical well-being. We have previously reported that pair bonding in monogamous prairie voles (Microtus ochrogaster) is prevented by a single prolonged stress (SPS) paradigm, which causes behavioral and endocrine symptoms resembling post-traumatic stress disorder (PTSD) patients in rats (Arai et al., 2016). Since fear memory function is crucial for anxiety-related disorders such as PTSD, we investigated the effects of pair bonding on fear learning in prairie voles. We applied an SPS paradigm to male prairie voles after the cohabitation with a male (cage-mate group) or female (pair-bonded group). The cage-mate group, but not the pair-bonded group, showed enhanced fear response in a contextual fear conditioning test following the SPS treatment. Immunohistochemical analyses revealed that cFos-positive cells in the central amygdala were increased in the pair-bonded group after the contextual fear conditioning test and that oxytocin immunoreactivity in the paraventricular nucleus of the hypothalamus was significantly higher in the pair-bonded group than the cagemate group. This pair-bonding dependent blunting of fear memory response was confirmed by a passive avoidance test, another fear-based learning test. Interestingly, intracerebroventricular injection of an oxytocin receptor antagonist 30 min before the passive avoidance test blocked the blunting effect of pair bonding on fear learning. Thus, pair bonding between socio-sexual partners results in social buffering in the absence of the partner, blunting fear learning, which may be mediated by oxytocin signaling.