Propranolol can induce PTSD-like memory impairments in rats.
Propranolol can induce PTSD-like memory impairments in rats.
复制标题
普萘洛尔可诱导大鼠出现类似 PTSD 的记忆障碍
DOI：
10.1002/brb3.905
复制
发表时间：
2018-03
影响因子：
3.1
通讯作者：
Zhao H
中科院分区：
文献类型：
--
作者：
Zhu RT;Liu XH;Shi YW;Wang XG;Xue L;Zhao H
创伤后应激障碍（PTSD）的一个标志性症状是无法将恐惧反应限制在适当的预测因素上。高强度休克后输注糖皮质激素（GC）已被证明会诱导PTSD样记忆障碍。除GC外，去甲肾上腺素能信号传导也被认为是PTSD病理学的关键生物标志物。为了探讨去甲肾上腺素能系统在PTSD样记忆障碍中的作用，在本研究中，在未配对线索-休克情境恐惧条件反射后立即将不同剂量的β-肾上腺素受体拮抗剂普萘洛尔全身或双侧注射到背侧海马中，然后在24 h后对大鼠进行测试。有趣的是，我们发现只有低剂量的普萘洛尔可以诱导PTSD样记忆障碍，因为大鼠表现出对正确预测的冻结减少和对安全提示的普遍恐惧反应，伴随着海马中NE水平的增加和额叶皮层下回路中神经活动的改变。这些发现表明去甲肾上腺素能系统参与调节情境恐惧记忆的巩固，普萘洛尔可剂量依赖性地诱导PTSD样记忆障碍。
One hallmark symptom of post‐traumatic stress disorder (PTSD) is an inability to restrict fear responses to the appropriate predictor. An infusion of glucocorticoids (GCs) after a high‐intensity shock has been shown to induce PTSD‐like memory impairments. In addition to GCs, noradrenergic signalling is also recognized as a key biomarker underlying PTSD symptomatology. To explore the role of the noradrenergic system in PTSD‐like memory impairments, in this study, various doses of the β‐adrenoceptor antagonist propranolol were systemically or bilaterally injected into the dorsal hippocampus immediately after unpaired cue‐shock contextual fear conditioning, and then the rats were tested 24 h later. Interestingly, we found that only low‐dose propranolol could induce PTSD‐like memory impairments, as rats showed reduced freezing to the correct predictor and generalized fear responses to the safe cues, accompanied by increased NE levels in the hippocampus and altered neural activity within the frontal‐subcortical circuit. These findings demonstrate that the noradrenergic system is involved in regulating the consolidation of contextual fear memory and that propranolol can dose‐dependently induce PTSD‐like memory impairments.
登录
查看更多内容
影响因子：
7.4
作者：
Geuze, Elbert;Vermetten, Eric;Westenberg, Herman G. M.
通讯作者：
Westenberg, Herman G. M.
影响因子：
4.7
作者：
Jovanovic T;Kazama A;Bachevalier J;Davis M
通讯作者：
Davis M
影响因子：
6
作者：
Bailey, Christopher R.;Cordell, Elisabeth;Sobin, Sean M.;Neumeister, Alexander
通讯作者：
Neumeister, Alexander
影响因子：
3
作者：
Barsegyan A;McGaugh JL;Roozendaal B
通讯作者：
Roozendaal B
影响因子：
5.3
作者：
Bernier, Brian E.;Lacagnina, Anthony F.;Drew, Michael R.
通讯作者：
Drew, Michael R.