Serotonin 2C receptors within the basolateral amygdala induce acute fear-like responses in an open-field environment

Serotonin 2C receptors within the basolateral amygdala induce acute fear-like responses in an open-field environment
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DOI:
10.1016/s0006-8993(03)03384-5
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发表时间:
2003-12-12
期刊:
影响因子:
2.9
通讯作者:
Merchant, KM
Merchant, KM
中科院分区:
医学3区
文献类型:
--
作者:
Campbell, BM;Merchant, KM

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一些研究表明,scrotonin 2亚家族(5-HT2A, 5-HT2B, 5-HT2C)在恐惧和焦虑反应的调解中起作用。目前的研究开始检测刺激杏仁核基底外侧(BLA)或中央核(CeA)内的5-HT2C受体对大鼠急性恐惧样反应的影响。双侧bla内输注混合5-HT2激动剂mCPP (3-3000 pmol),可产生超声发声,减少探索行为,同时增加探索新物体的潜伏期。这些反应被5- ht2c特异性拮抗剂SB-242084减弱。此外,一种选择性5-HT2C激动剂IL-639也产生了类似的行为效应,除了对在露天场地中心停留时间的影响。最后,将mCPP输注到CeA中没有产生焦虑性行为,这表明主要位于BLA内的5-HT2C受体是许多急性恐惧样反应的原因。为了进一步表征与5- ht2c介导的恐惧反应相关的神经回路,我们评估了在bla内注射mCPP、IL-639或其载体后c-fos mRNA的表达。尽管这两种药物诱导c-fos mRNA的整体区域模式不同,但c-fos的激活主要局限于边缘核,而内侧前额叶皮层是每种药物的共同区域靶点。这些结果表明,BLA内5-HT2C受体的激活影响了参与急性先天恐惧反应表达的边缘回路的活性。(C) 2003, Elsevier B.V.出版
Several studies indicate a role for the scrotonin 2 subfamily (5-HT2A, 5-HT2B, 5-HT2C in mediation of fear and anxiety responses. The current study began to examine the effects of stimulating 5-HT2C receptors within the basolateral (BLA) or central nucleus of the amygdala (CeA) on acute fear-like responses in rats. Bilateral intra-BLA infusions of mCPP (3-3000 pmol), a mixed 5-HT2 agonist, produced ultrasonic vocalization and reduced exploratory behavior while increasing the latency to investigate a novel object. These responses were attenuated by SB-242084, a 5-HT2C-specific antagonist. Furthermore, a selective 5-HT2C agonist, IL-639, produced a similar repertoire of behavioral effects with the exception of effects on time spent in the center of an open-field arena. Finally, infusions of mCPP into the CeA produced no anxiogenic behaviors suggesting that 5-HT2C receptors primarily within the BLA are responsible for many of the acute fear-like responses reported here.To characterize further the neural circuits associated with 5-HT2C-mediated fear responses, we assessed c-fos mRNA expression after intra-BLA infusions of mCPP, IL-639 or their vehicles. Whereas the overall regional pattern of c-fos mRNA induction for the two compounds was distinct, c-fos activation was confined primarily to limbic nuclei with the medial prefrontal cortex as a common regional target of each drug. These results suggest that activation of 5-HT2C receptors within the BLA influences the activity of limbic circuits involved in the expression of acute innate fear responses. (C) 2003 Published by Elsevier B.V.