Nitric oxide (NO) release in the right medial prefrontal cortex (RmPFC) produces anxiogenesis. In the bed nucleus of the stria terminalis (BNST), a region that receives neuronal projections from the mPFC, NO provokes anxiety, an effect that is blocked by local injections of corticotrophin-releasing factor type 1 receptor (CRF1) or n-methyl-d-aspartate receptor (NMDAr) antagonist. Anxiety is also enhanced by social defeat stress, and chronic stress impairs and facilitates, respectively, PFC and BNST roles in modulating behavioral responses to aversive situations. This study investigated whether the (i) chronic social defeat stress (CSDS) increases NO signaling in the mPFC; and/or (ii) anxiogenic effects provoked by the intra-RmPFC injection of NOC-9 (an NO donor) or by CSDS are prevented by intra-BNST injections of AP-7 (0.05 nmol) or CP 376395 (3.0 nmol), respectively, NMDAr and CRF1 antagonists, in male Swiss-Webster mice exposed to the elevated plus-maze (EPM). Results showed that (a) CSDS increased anxiety (i.e., reduced open-arm exploration) and repeatedly activated nNOS-containing neurons, as measured by ΔFosB (a stable nonspecific marker of neural activity) + nNOS double-labeling, in the right (but not left) mPFC, (b) NOC-9 in the RmPFC also increased anxiety, and (c) both CSDS and NOC-9 effects were reversed by injections of AP-7 or CP 376395 into the BNST. These results suggest that NMDA and CRF1 receptors located in BNST play an important role in the modulation of anxiety provoked by NO in the RmPFC, as well as by chronic social defeat in mice.

中文翻译：

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在雄性小鼠中由社交失败引起的血管生成：一氧化氮，NMDA和CRF1受体在内侧前额叶皮层和BNST中的作用。

右内侧前额叶皮层（RmPFC）中释放的一氧化氮（NO）会产生血管生成。在纹状体终末床（BNST）的床核中，该区域接受来自mPFC的神经元投射，NO引起焦虑，这种效应被局部注射促肾上腺皮质激素释放因子1型受体（CRF1）或正甲基d-天冬氨酸受体（NMDAr）拮抗剂。社交挫败压力也加剧了焦虑，慢性压力分别削弱和促进了PFC和BNST在调节对厌恶状况的行为反应中的作用。这项研究调查（i）慢性社交挫败压力（CSDS）是否增加mPFC中的NO信号传导；和/或（ii）BNST内注射AP-7（0.05 nmol）或CP 376395可防止RmPFC内注射NOC-9（NO供体）或CSDS引起的焦虑作用（3。在暴露于高迷宫（EPM）的雄性Swiss-Webster小鼠中，分别将NMDAr和CRF1拮抗剂分别设为0 nmol）。结果表明：（a）CSDS在右侧增加了焦虑（即减少了开臂探查）并反复激活了包含nNOS的神经元（通过ΔFosB（稳定的神经活动非特异性标记）+ nNOS双重标记进行了测量。未留下）mPFC，（b）RmPFC中的NOC-9也增加了焦虑，并且（c）通过向BNST中注射AP-7或CP 376395，可逆转CSDS和NOC-9的作用。这些结果表明，位于BNST中的NMDA和CRF1受体在调节RmPFC中NO引起的焦虑以及小鼠慢性社交衰竭中起重要作用。结果表明：（a）CSDS在右侧增加了焦虑（即减少了开臂探查）并反复激活了包含nNOS的神经元（通过ΔFosB（稳定的神经活动非特异性标记）+ nNOS双重标记进行了测量。未留下）mPFC，（b）RmPFC中的NOC-9也增加了焦虑，并且（c）通过向BNST中注射AP-7或CP 376395，可逆转CSDS和NOC-9的作用。这些结果表明，位于BNST中的NMDA和CRF1受体在调节RmPFC中NO引起的焦虑以及小鼠慢性社交衰竭中起重要作用。结果表明：（a）CSDS在右侧增加了焦虑（即减少了开臂探查）并反复激活了包含nNOS的神经元（通过ΔFosB（稳定的神经活动非特异性标记）+ nNOS双重标记进行了测量。未留下）mPFC，（b）RmPFC中的NOC-9也增加了焦虑，并且（c）通过向BNST中注射AP-7或CP 376395，可逆转CSDS和NOC-9的作用。这些结果表明，位于BNST中的NMDA和CRF1受体在调节RmPFC中NO引起的焦虑以及小鼠慢性社交衰竭中起重要作用。（b）RmPFC中的NOC-9也增加了焦虑，并且（c）通过向BNST中注射AP-7或CP 376395，可以逆转CSDS和NOC-9的作用。这些结果表明，位于BNST中的NMDA和CRF1受体在调节RmPFC中NO引起的焦虑以及小鼠慢性社交衰竭中起重要作用。（b）RmPFC中的NOC-9也增加了焦虑，并且（c）通过向BNST中注射AP-7或CP 376395，可以逆转CSDS和NOC-9的作用。这些结果表明，位于BNST中的NMDA和CRF1受体在调节RmPFC中NO引起的焦虑以及小鼠慢性社交衰竭中起重要作用。