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前额叶皮质5-羟色胺能神经支配的背内侧部分在大鼠对厌恶条件化环境反应中的作用:行为学、生物化学和免疫细胞化学研究

The role of the dorsomedial part of the prefrontal cortex serotonergic innervation in rat responses to the aversively conditioned context: behavioral, biochemical and immunocytochemical studies.

作者信息

Lehner Małgorzata, Taracha Ewa, Turzyńska Danuta, Sobolewska Alicja, Hamed Adam, Kołomańska Paulina, Skórzewska Anna, Maciejak Piotr, Szyndler Janusz, Bidziński Andrzej, Płaźnik Adam

机构信息

Department of Neurochemistry, Institute of Psychiatry and Neurology, 9 Sobieskiego Street, 02-957 Warsaw, Poland.

出版信息

Behav Brain Res. 2008 Oct 10;192(2):203-15. doi: 10.1016/j.bbr.2008.04.003. Epub 2008 Apr 16.

Abstract

In this study we have explored differences in animal reactivity to conditioned aversive stimuli using the conditioned fear test (a contextual fear-freezing response), in rats subjected to the selective lesion of the prefrontal cortex serotonergic innervation, and differing in their response to the acute painful stimulation, a footshock (HS--high sensitivity rats, and LS--low sensitivity rats, selected arbitrarily according to their behavior in the 'flinch-jump' pre-test). Local administration of serotonergic neurotoxin (5,7-dihydroxytryptamine) to the dorsomedial part of the prefrontal cortex caused a very strong, structure and neurotransmitter selective depletion of serotonin concentration. In HS rats, the serotonergic lesion significantly disinhibited rat behavior controlled by fear, enhanced c-Fos expression in the dorsomedial prefrontal area, and increased the concentration of GABA in the basolateral amygdala, measured in vivo after the testing session of the conditioned fear test. The LS animals revealed an opposite pattern of behavioral and biochemical changes after serotonergic lesion: an increase in the duration of a freezing response, and expression of c-Fos in the basolateral and central nuclei of amygdala, and a lower GABA concentration in the basolateral amygdala. In control conditions, c-Fos expression did not differ in LS and HS, naïve, not conditioned and not exposed to the test cage animals. The present study adds more arguments for the controlling role of serotonergic innervation of the dorsomedial part of the prefrontal cortex in processing emotional input by other brain centers. Moreover, it provides experimental data, which may help to better explain the anatomical and biochemical basis of differences in individual reactivity to stressful stimulation, and, possibly, to anxiolytic drugs with serotonergic or GABAergic profiles of action.

摘要

在本研究中,我们利用条件性恐惧测试(一种情境性恐惧 - 僵住反应),探讨了前额叶皮质5-羟色胺能神经支配选择性损伤的大鼠对条件性厌恶刺激的动物反应差异,这些大鼠对急性疼痛刺激(足部电击,根据它们在“退缩 - 跳跃”预测试中的行为任意选择的高敏感性大鼠(HS)和低敏感性大鼠(LS))的反应也不同。向前额叶皮质背内侧部分局部施用5-羟色胺能神经毒素(5,7 - 二羟基色胺)导致5-羟色胺浓度非常强烈、结构和神经递质选择性的耗竭。在HS大鼠中,5-羟色胺能损伤显著解除了恐惧对大鼠行为的抑制,增强了背内侧前额叶区域的c-Fos表达,并在条件性恐惧测试的测试阶段后在体内测量到基底外侧杏仁核中的γ-氨基丁酸(GABA)浓度增加。5-羟色胺能损伤后,LS动物表现出相反的行为和生化变化模式:僵住反应持续时间增加,杏仁核基底外侧和中央核中c-Fos表达增加,基底外侧杏仁核中GABA浓度降低。在对照条件下,LS和HS、未处理、未条件化且未暴露于测试笼的动物的c-Fos表达没有差异。本研究为前额叶皮质背内侧部分的5-羟色胺能神经支配在其他脑中心处理情绪输入中的控制作用提供了更多论据。此外,它提供了实验数据,这可能有助于更好地解释个体对应激刺激反应差异的解剖学和生化基础,以及可能有助于更好地解释具有5-羟色胺能或GABA能作用谱的抗焦虑药物。

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