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抑郁的遗传大鼠模型中的情绪记忆损伤：5-HT/MEK/Arc 信号转导在恢复中的作用。

Emotional memory impairments in a genetic rat model of depression: involvement of 5-HT/MEK/Arc signaling in restoration.

机构信息

Center of Molecular Medicine, Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.

出版信息

Mol Psychiatry. 2012 Feb;17(2):173-84. doi: 10.1038/mp.2010.131. Epub 2011 Jan 18.

DOI:10.1038/mp.2010.131
PMID:21242991
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3265836/
Abstract

Cognitive dysfunctions are common in major depressive disorder, but have been difficult to recapitulate in animal models. This study shows that Flinders sensitive line (FSL) rats, a genetic rat model of depression, display a pronounced impairment of emotional memory function in the passive avoidance (PA) task, accompanied by reduced transcription of Arc in prefrontal cortex and hippocampus. At the cellular level, FSL rats have selective reductions in levels of NMDA receptor subunits, serotonin 5-HT(1A) receptors and MEK activity. Treatment with chronic escitalopram, but not with an antidepressant regimen of nortriptyline, restored memory performance and increased Arc transcription in FSL rats. Multiple pharmacological manipulations demonstrated that procognitive effects could also be achieved by either disinhibition of 5-HT(1A)R/MEK/Arc or stimulation of 5-HT₄R/MEK/Arc signaling cascades. Taken together, studies of FSL rats in the PA task revealed reversible deficits in emotional memory processing, providing a potential model with predictive and construct validity for assessments of procognitive actions of antidepressant drug therapies.

摘要

认知功能障碍在重度抑郁症中很常见，但在动物模型中很难重现。本研究表明，弗林德斯敏感系（FSL）大鼠，一种抑郁症的遗传大鼠模型，在被动回避（PA）任务中表现出明显的情绪记忆功能障碍，同时前额叶皮层和海马体中的 Arc 转录减少。在细胞水平上，FSL 大鼠 NMDA 受体亚单位、5-羟色胺 5-HT（1A）受体和 MEK 活性选择性降低。用慢性依地普仑治疗，但不是用去甲替林的抗抑郁治疗方案治疗，可恢复 FSL 大鼠的记忆表现并增加 Arc 转录。多项药理学操作表明，通过抑制 5-HT（1A）R/MEK/Arc 或刺激 5-HT₄R/MEK/Arc 信号转导，也可以获得认知促进作用。总之，在 PA 任务中对 FSL 大鼠的研究揭示了情绪记忆处理的可逆缺陷，为评估抗抑郁药物治疗的认知促进作用提供了一个具有预测性和构建效度的潜在模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0df/3265836/805ed362ef53/mp2010131f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0df/3265836/5576c3bb3fa4/mp2010131f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0df/3265836/3c8ea0141708/mp2010131f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0df/3265836/ea7a69c8209b/mp2010131f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0df/3265836/d158a1d2d747/mp2010131f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0df/3265836/805ed362ef53/mp2010131f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0df/3265836/5576c3bb3fa4/mp2010131f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0df/3265836/3c8ea0141708/mp2010131f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0df/3265836/ea7a69c8209b/mp2010131f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0df/3265836/d158a1d2d747/mp2010131f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0df/3265836/805ed362ef53/mp2010131f5.jpg

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