Serotonergic mechanisms of the median raphe nucleus-dorsal hippocampus in conditioned fear: Output circuit involves the prefrontal cortex and amygdala
Serotonergic mechanisms of the median raphe nucleus-dorsal hippocampus in conditioned fear: Output circuit involves the prefrontal cortex and amygdala
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DOI：
10.1016/j.bbr.2009.05.017
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发表时间：
2009-11-05
影响因子：
2.7
通讯作者：
Brandao, Marcus L.
中科院分区：
文献类型：
--
作者：
Almada, Rafael C.;Borelli, Karina G.;Brandao, Marcus L.
独立研究表明，中缝正中核(MRN)和背侧海马区(DH)参与语境条件性恐惧(CFC)的表达。然而，研究MRN-DH的5-羟色胺能机制的综合参与的研究是缺乏的。为了解决这个问题，使用了一种CFC范式来测试从MRN到DH的5-羟色胺能投射是否会影响CFC。在测试之前，将5-羟色胺能药物注入MRN或DH，在相同的环境中测量冰冻和惊吓反应，与6h之前大鼠接受足击的情况相同。局部注射5-羟色胺(5-羟色胺)激动剂8-羟基-2-(二正丙氨基)四氢呋喃(8-OH-DPAT)可减少5-羟色胺(5-HT)在MRN的传递，减少冰冻反应，但不能减少恐惧增强的惊吓。这一结果模式与MRN 5-羟色胺能机制选择性地调节对厌恶环境的冻结反应的假设是一致的。至于背核，投射区域突触后5-羟色胺受体活性的降低被认为是MIRN 5-HT1a受体激活的主要结果。Dh内注射8-OH-DPAT既能抑制冰冻反应，又能抑制对环境的惊吓反应。为了与这些发现相一致，在从MRN到DH的传入5-羟色胺通路和DH向其他结构输出的神经元之间可能存在一种抑制机制。杏仁核或内侧前额叶皮质的投射很可能就是这个输出回路，通过测量这些区域的Fos免疫反应性来调节CFC的表达。(C)2009爱思唯尔B.V.保留所有权利。
Independent studies have shown that the median raphe nucleus (MRN) and dorsal hippocampus (DH) are involved in the expression of contextual conditioned fear (CFC). However, studies that examine the integrated involvement of serotonergic mechanisms of the MRN-DH are lacking. To address this issue, a CFC paradigm was used to test whether the serotonergic projections from the MRN to DH can influence CFC. Serotoninergic drugs were infused either into the MRN or DH prior to testing sessions in which freezing and startle responses were measured in the same context where 6 h previously rats received footshocks. A reduction of serotonin (5-HT) transmission in the MRN by local infusions of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) decreased freezing in response to the context but did not reduce fear-potentiated startle. This pattern of results is consistent with the hypothesis that MRN serotonergic mechanisms selectively modulate the freezing response to the aversive context. As for the DH, a decrease in postsynaptic 5-HT receptor activity at projection areas has been proposed to be the main consequence of 5-HT1A receptor activation in the MIRN. Intra-DH injections of 8-OH-DPAT inhibited both the freezing and fear-potentiated startle response to the context. To reconcile these findings, an inhibitory mechanism may exist between the incoming 5-HT pathway from the MRN to DH and the neurons of the DH output to other structures. The DH-amygdala or medial prefrontal cortex projections could well be this output circuit modulating the expression of CFC as revealed by measurements of Fos immunoreactivity in these areas. (C) 2009 Elsevier B.V. All rights reserved.