Traumatic stress causes distinctive effects on fear circuit catecholamines and the fear extinction profile in a rodent model of posttraumatic stress disorder
Traumatic stress causes distinctive effects on fear circuit catecholamines and the fear extinction profile in a rodent model of posttraumatic stress disorder
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DOI：
10.1016/j.euroneuro.2016.06.004
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发表时间：
2016-09-01
影响因子：
5.6
通讯作者：
Liu, Yia-Ping
中科院分区：
文献类型：
--
作者：
Lin, Chen-Cheng;Tung, Che-Se;Liu, Yia-Ping
中枢儿茶酚胺调节内侧前额叶皮质(MPFC)、杏仁核(AMYG)和海马区(HPC)的恐惧记忆。然而，就创伤后应激障碍(PTSD)的恐惧症状而言，没有足够的证据来解决这些恐惧回路区域之间的关系。通过检测单次持续应激大鼠(创伤后应激大鼠模型)在巴甫洛夫恐惧条件反射范式中的行为特征、组织/外流多巴胺(DA)和去甲肾上腺素(NE)水平以及它们在恐惧环路区域的重摄取能力，我们证明了SPS损害的消退恢复以一种分离的方式伴随着中枢DA/NE的变化。在组织水平上，mPFC和AMYG的DA减少，NE增加。AMYG/vHPC的DA外流和突触体DA转运体持续减少，而SPS则减少下缘皮质的NE外流和mPFC的突触体NE转运体。此外，SPS后，突触小体VMAT2在mPFC、AMYG和vHPC中的表达较低。最后，在mPFC/AMYG中，提取冻结与DA呈负相关；然而，这种现象在SPS后变得无效。我们的结果表明，中枢儿茶酚胺在恐惧消退的恢复过程中起着至关重要的作用，DA和NE在整个恐惧环路区域扮演着不同的角色。(C)2016年爱思唯尔和ECNP。版权所有。
Central catecholamines regulate fear memory across the medial prefrontal cortex (mPFC), amygdala (AMYG), and hippocampus (HPC). However, inadequate evidence exists to address the relationships among these fear circuit areas in terms of the fear symptoms of posttraumatic stress disorder (PTSD). By examining the behavioral profile in a Pavlovian fear conditioning paradigm together with tissue/ efflux levels of dopamine (DA) and norepinephrine (NE) and their reuptake abilities across the fear circuit areas in rats that experienced single prolonged stress (SPS, a rodent model of PTSD), we demonstrated that SPS-impaired extinction retrieval was concomitant with the changes of central DA/NE in a dissociable manner. For tissue levels, diminished DA and increased NE were both observed in the mPFC and AMYG. DA efflux and synaptosomal DA transporter were consistently reduced in the AMYG/vHPC, whereas SPS reduced NE efflux in the infralimbic cortex and synaptosomal NE transporter in the mPFC. Furthermore, a lower expression of synaptosomal VMAT2 was observed in the mPFC, AMYG, and vHPC after SPS. Finally, negative correlations were observed between retrieval freezing and DA in the mPFC/AMYG; nevertheless, the phenomena became invalid after SPS. Our results suggest that central catecholamines are crucially involved in the retrieval of fear extinction in which DA and NE play distinctive roles across the fear circuit areas. (C) 2016 Elsevier B.V. and ECNP. All rights reserved.