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阻断毒蕈碱受体通过减少胆碱能神经传递来损害旧恐惧记忆的再巩固:创伤后应激障碍大鼠模型的研究。

Blockade of muscarinic receptors impairs reconsolidation of older fear memory by decreasing cholinergic neurotransmission: A study in rat model of PTSD.

机构信息

Neurochemistry and Biochemical Neuropharmacology Research Unit, Department of Biochemistry, University of Karachi, Karachi 75270, Pakistan.

Dr. Panjwani Center for Molecular Medicine and Drug Research International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.

出版信息

Life Sci. 2020 Sep 1;256:118014. doi: 10.1016/j.lfs.2020.118014. Epub 2020 Jun 25.

DOI:10.1016/j.lfs.2020.118014
PMID:32593712
Abstract

The age and strength of fear memory are two potential parameters that can be influenced by the impairing effects of pharmacological agents on reconsolidation of fear memory. In reconsolidation, stored information is rendered labile again after being reactivated. Pharmacological manipulations at this stage result in an inability to retrieve the fear memories, suggesting that they are erased or persistently inhibited. This fear memory impairment phenomenon can be valuable to treat post-traumatic stress disorders (PTSD). Previously β-adrenergic antagonist propranolol has been repeatedly reported to impair fear memory in the treatment of PTSD. Atropine has also shown to disrupt memory formation. The present study was therefore designed to compare the effects of atropine and propranolol on reconsolidation of older fear memory in rat model of PTSD using Pavlovian fear conditioning apparatus. For this purpose 18 rats were taken and divided into control, atropine and propranolol groups and subjected to Pavlovian fear conditioning trials in order to develop animal model of PTSD. To evaluate the reconsolidation impairment of fear memory by atropine and propranolol, short term and long term memory was tested after reactivation of fear memory in rats. The present findings demonstrate that atropine significantly decreases fear expression. These results suggest that atropine significantly reduces the strength of fear memories and may be effective in the treatment of psychiatric disorders especially in PTSD.

摘要

恐惧记忆的年龄和强度是两个潜在的参数,可以通过药理学药物对恐惧记忆再巩固的损害作用来影响。在再巩固过程中,存储的信息在被重新激活后再次变得不稳定。在此阶段进行药理学操作会导致无法检索恐惧记忆,表明它们被抹去或持续受到抑制。这种恐惧记忆损伤现象对于治疗创伤后应激障碍(PTSD)可能很有价值。先前已经有报道称,β-肾上腺素能拮抗剂普萘洛尔在治疗 PTSD 时反复被证明可以损害恐惧记忆。阿托品也显示出干扰记忆形成的作用。因此,本研究旨在使用巴甫洛夫恐惧条件反射装置比较阿托品和普萘洛尔对 PTSD 大鼠模型中较旧恐惧记忆再巩固的影响。为此,取 18 只大鼠并分为对照组、阿托品组和普萘洛尔组,进行巴甫洛夫恐惧条件反射试验,以建立 PTSD 的动物模型。为了评估阿托品和普萘洛尔对恐惧记忆再巩固的损害作用,在大鼠恐惧记忆再激活后测试短期和长期记忆。本研究结果表明,阿托品显著降低了恐惧表达。这些结果表明,阿托品显著降低了恐惧记忆的强度,可能对治疗精神障碍,特别是 PTSD 有效。

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