National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India.
Biol Psychiatry. 2012 Sep 15;72(6):466-75. doi: 10.1016/j.biopsych.2012.04.008. Epub 2012 May 8.
A single episode of acute immobilization stress has previously been shown to trigger a delayed onset of anxiety-like behavior and spinogenesis in the basolateral amygdala (BLA) of rats. Spurred on by a seemingly paradoxical observation in which even a modest increase in corticosterone (CORT), caused by a single vehicle injection before stress, could dampen the delayed effects of stress, we hypothesized a protective role for glucocorticoids against stress.
We tested this hypothesis by analyzing how manipulations in CORT levels modulate delayed increase in anxiety-like behavior of rats on the elevated plus-maze 10 days after acute stress. We also investigated the cellular correlates of different levels of anxiety under different CORT conditions by quantifying spine density on Golgi-stained BLA principal neurons.
CORT in drinking water for 12 hours preceding acute stress prevented delayed increase in anxiety rather than exacerbating it. Conversely, vehicle injection failed to prevent the anxiogenic effect of stress in bilaterally adrenalectomized rats. However, when CORT was restored in adrenalectomized rats by injection, the delayed anxiogenic effect of stress was once again blocked. Finally, high and low anxiety states were accompanied by high and low levels of BLA spine density.
Our findings suggest that the presence of elevated levels of CORT at the time of acute stress confers protection against the delayed enhancing effect of stress on BLA synaptic connectivity and anxiety-like behavior. These observations are consistent with clinical reports on the protective effects of glucocorticoids against the development of posttraumatic symptoms triggered by traumatic stress.
先前的研究表明，单次急性束缚应激可引发大鼠基底外侧杏仁核（BLA）中焦虑样行为和 spinogenesis 的延迟发作。由于一个看似矛盾的观察结果，即在应激前单次注射车辆即可导致皮质酮（CORT）适度增加，从而抑制应激的延迟效应，这激发了我们对糖皮质激素对抗应激的保护作用的假设。
我们通过分析 CORT 水平的操纵如何调节急性应激后 10 天大鼠在高架十字迷宫上焦虑样行为的延迟增加，来检验这一假设。我们还通过量化不同 CORT 条件下 BLA 主神经元上的棘突密度，研究了不同 CORT 条件下不同焦虑水平的细胞相关性。
在急性应激前 12 小时在饮用水中添加 CORT 可预防而不是加剧焦虑的延迟增加。相反，在双侧肾上腺切除术大鼠中，车辆注射未能预防应激的致焦虑作用。然而，当 CORT 通过注射在肾上腺切除术大鼠中恢复时，应激的延迟致焦虑作用再次被阻断。最后，高和低焦虑状态伴随着 BLA 棘突密度的高和低水平。
我们的发现表明，在急性应激时存在升高的 CORT 水平可提供对 BLA 突触连接和焦虑样行为的应激延迟增强作用的保护。这些观察结果与临床报告一致，即糖皮质激素对创伤性应激引发的创伤后症状发展具有保护作用。
