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普萘洛尔可诱导大鼠出现 PTSD 样记忆损伤。

Propranolol can induce PTSD-like memory impairments in rats.

机构信息

Faculty of Forensic Medicine Zhongshan School of Medicine Sun Yat-Sen University Guangzhou China.

Guangdong Province Key Laboratory of Brain Function and Disease Zhongshan School of Medicine Sun Yat-Sen University Guangzhou China.

出版信息

Brain Behav. 2018 Jan 18;8(2):e00905. doi: 10.1002/brb3.905. eCollection 2018 Feb.

Abstract

INTRODUCTION

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

简介

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器上。高强度休克后注入糖皮质激素(GCs)已被证明会导致类似 PTSD 的记忆损伤。除了 GCs,去甲肾上腺素信号也被认为是 PTSD 症状的关键生物标志物。

方法

为了探索去甲肾上腺素系统在类似 PTSD 的记忆损伤中的作用,在这项研究中,各种剂量的β-肾上腺素受体拮抗剂普萘洛尔在非配对线索-休克情境恐惧条件反射后立即系统或双侧注射到背侧海马体,然后在 24 小时后对大鼠进行测试。

结果

有趣的是,我们发现只有低剂量的普萘洛尔才能诱导出类似 PTSD 的记忆损伤,因为大鼠对正确预测器的冻结反应减少,对安全线索的泛化恐惧反应增加,同时海马体中的去甲肾上腺素水平升高,额叶-皮质下回路中的神经活动改变。

结论

这些发现表明,去甲肾上腺素系统参与调节情境恐惧记忆的巩固,并且普萘洛尔可以剂量依赖性地诱导类似 PTSD 的记忆损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1575/5822589/5e8a6a9667cb/BRB3-8-e00905-g001.jpg

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