Habituation to repeated restraint stress is associated with lack of stress-induced c-fos expression in primary sensory processing areas of the rat brain

Habituation to repeated restraint stress is associated with lack of stress-induced c-fos expression in primary sensory processing areas of the rat brain
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DOI:
10.1016/j.neuroscience.2005.12.002
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发表时间:
2006-01-01
期刊:
影响因子:
3.3
通讯作者:
Spencer, RL
Spencer, RL
中科院分区:
医学3区
文献类型:
--
作者:
Girotti, M;Pace, TWW;Spencer, RL

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反复暴露于束缚的大鼠在再次暴露于束缚时表现出下丘脑-垂体-肾上腺轴反应降低。这种下丘脑-垂体-广告肾轴对约束的反应习惯并不能推广到其他新的压力源。并且与许多应激反应性大脑区域中应激诱导的 c-fos 表达减少有关。我们研究了对反复束缚的习惯是否也与处理和传递初级感觉信息的大脑区域的早期基因表达的适应有关。这些大脑区域可能不会表现出对重复限制的基因表达适应,因为它们在经验歧视中发挥着必要的作用。将大鼠分为重复约束组(每天 5 次每次 1 小时的约束组)和无压力组(未施加约束)。第六天,每组大鼠要么在没有额外应激经历的情况下被处死,要么在束缚期间 15、30 或 60 分钟处死。通过原位杂交测定立即早期基因表达(促肾上腺皮质激素释放激素异核RNA、c-fos mRNA、zif268 mRNA)。与未受约束的动物相比,在重复约束中观察到应激诱导的下丘脑-垂体-肾上腺轴激素分泌(血浆皮质酮和促肾上腺皮质激素)以及下丘脑室旁核、外侧隔膜和眼眶皮质中即刻早期基因表达水平的减少。这种减少在 15 分钟的约束下就已经很明显了。出乎意料的是,我们还发现,在反复束缚的大鼠中,束缚诱导的初级感觉处理脑区(初级体感皮层、丘脑腹后内侧和背外侧膝状核)中 c-fos 表达减少。海马盐皮质激素受体异核 RNA 或糖皮质激素受体 mRNA 的总体水平不会因重复限制而降低,这可能是对严重慢性应激的反应。我们认为,重复的约束会导致系统级的适应,从而重新暴露于约束会引发初级感觉处理的快速抑制性调节(即感觉门控),从而产生对约束的神经反应的广泛衰减。 (C) 2005 年由 Elsevier Ltd 代表 IBRO 出版。
Rats repeatedly exposed to restraint show a reduced hypothalamic-pituitary-adrenal axis response upon restraint re-exposure. This hypothalamic-pituitary-ad renal axis response habituation to restraint does not generalize to other novel stressors; and is associated with a decrease in stress-induced c-fos expression in a number of stress-reactive brain regions. We examined whether habituation to repeated restraint is also associated with adaptation of immediate early gene expression in brain regions that process and relay primary sensory information. These brain regions may not be expected to show gene expression adaptation to repeated restraint because of their necessary role in experience discrimination. Rats were divided into a repeated restraint group (five 1-hour daily restraint sessions) and an unstressed group (restraint naive). On the sixth day rats from each group were either killed with no additional stress experience or at 15, 30 or 60 min during restraint. Immediate early gene expression (corticotrophin-releasing hormone heteronuclear RNA, c-fos mRNA, zif268 mRNA) was determined by in situ hybridization. A reduction in stress-induced hypothalamic-pituitary-adrenal axis hormone secretion (plasma corticosterone and adrenocorticotropic hormone) and immediate early gene expression levels in the paraventricular nucleus of the hypothalamus, the lateral septum and the orbital cortex was observed in repeated restraint as compared with restraint naive animals. This reduction was already evident at 15 min of restraint. Unexpectedly, we also found in repeated restraint rats a reduction in restraint-induced c-fos expression in primary sensory-processing brain areas (primary somatosensory cortex, and ventroposteriomedial and dorsolateral geniculate nuclei of thalamus). The overall levels of hippocampal mineralocorticoid receptor heteronuclear RNA or glucocorticoid receptor mRNA were not decreased by repeated restraint, as may occur in response to severe chronic stress. We propose that repeated restraint leads to a systems-level adaptation whereby re-exposure to restraint elicits a rapid inhibitory modulation of primary sensory processing (i.e. sensory gating), thereby producing a widespread attenuation of the neural response to restraint. (C) 2005 Published by Elsevier Ltd on behalf of IBRO.