Sex-Specific Effects of Stress on Oxytocin Neurons Correspond With Responses to Intranasal Oxytocin.
Sex-Specific Effects of Stress on Oxytocin Neurons Correspond With Responses to Intranasal Oxytocin.
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DOI：
10.1016/j.biopsych.2015.10.007
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发表时间：
2016-09-01
影响因子：
10.6
通讯作者：
Trainor BC
中科院分区：
文献类型：
--
作者：
Steinman MQ;Duque-Wilckens N;Greenberg GD;Hao R;Campi KL;Laredo SA;Laman-Maharg A;Manning CE;Doig IE;Lopez EM;Walch K;Bales KL;Trainor BC
催产素（OT）被认为是一种压力缓冲激素，抑制压力的生理效应。然而，OT也可以是焦虑的。我们在雄性和雌性加州小鼠中研究了社会失败对OT神经元的急性和长期影响。我们用免疫组织化学方法检测了OT和c-fos在失败后立即（n = 6-9）以及两周（n = 6-9）和十周（n = 4-5）后的OT神经元活性。我们用qPCR定量Oxt mRNA（n = 5-9）。将鼻内OT施用于在社交互动和居民-入侵者测试中测试的幼稚和应激小鼠（n = 8-14）。急性暴露于第三次发作的失败增加OT/c-fos共定位在室旁核（PVN）的两种性别。在终纹的中腹床核（BNSTmv），失败增加Oxt mRNA，总OT神经元，OT/c-fos共定位在女性，但不男性。鼻内OT未能逆转压力诱导的女性社交退缩，并减少了女性的社会互动行为。相比之下，鼻内OT增加了社会交往的压力男性和减少冻结的居民入侵者测试。社会失败诱导长期持久的增加OT生产和OT/c-fos细胞的BNSTmv的女性，但不是男性。鼻内OT在很大程度上扭转了男性行为的压力的影响，但在女性的影响是混合的。这些结果表明，OT敏感网络的变化有助于性别差异的行为反应的压力。
Oxytocin (OT) is considered to be a stress buffering hormone, dampening the physiological effects of stress. However, OT can also be anxiogenic. We examined acute and long lasting effects of social defeat on OT neurons in male and female California mice. We used immunohistochemistry for OT and c-fos to examine OT neuron activity immediately after defeat (n = 6-9) as well as two (n = 6-9) and ten weeks (n = 4-5) later. We quantified Oxt mRNA with qPCR (n = 5-9). Intranasal OT was administered to naïve and stressed mice tested in social interaction and resident-intruder tests (n = 8-14). Acute exposure to a third episode of defeat increased OT/c-fos colocalizations in the paraventricular nucleus (PVN) of both sexes. In the medioventral bed nucleus of the stria terminalis (BNSTmv), defeat increased Oxt mRNA, total OT neurons, and OT/c-fos colocalizations in females but not males. Intranasal OT failed to reverse stress-induced social withdrawal in females, and reduced social interaction behavior in females naïve to defeat. In contrast, intranasal OT increased social interaction in stressed males and reduced freezing in the resident-intruder test. Social defeat induces long lasting increases in OT production and OT/c-fos cells in the BNSTmv of females but not males. Intranasal OT largely reversed effects of stress on behavior in males but effects were mixed in females. These results suggest changes in OT sensitive networks contribute to sex differences in behavioral responses to stress.