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证明神经元型一氧化氮合酶和可溶性鸟苷酸环化酶参与大鼠的认知功能。

Evidence for the involvement of neuronal nitric oxide synthase and soluble guanylate cyclase on cognitive functions in rats.

机构信息

Department of Pharmacology, Faculty of Medicine and Experimental Medical Research and Application Center, Kocaeli University, Kocaeli, Turkey.

出版信息

Life Sci. 2011 Dec 5;89(23-24):905-10. doi: 10.1016/j.lfs.2011.09.017. Epub 2011 Oct 2.

Abstract

AIMS

The influence of 3-bromo-7-nitroindazole (3-Br 7-NI), a potent and selective neuronal nitric oxide synthase (nNOS) inhibitor, and [1H-[1,2,4]-oxadiazole[4,3a]-quinoxaline-1-one] (ODQ), a highly selective, irreversible inhibitor of soluble guanylate cyclase (sGC), on working and reference memory and emotional learning was investigated in rats.

MAIN METHODS

The effects were assessed in the three-panel runway and step-down passive avoidance task, respectively.

KEY FINDINGS

3-Br 7-NI (5, 10, and 20mg/kg) and ODQ (5, 10, and 20mg/kg) significantly increased the number of errors and latency of both working and reference memory performance of rats and impaired retention for the passive avoidance task. The effect of 3-Br 7-NI was reversed by l-arginine (250 mg/kg).

SIGNIFICANCE

Findings of the study supported the hypothesis that nNOS inhibition disrupts reference and working memory processes in terms of an impairment in the strategies used for solving learning tasks, and, according to these results, nNOS-sGC may be required for emotional learning and both reference and working memory.

摘要

目的

研究强效且选择性的神经元型一氧化氮合酶(nNOS)抑制剂 3-溴-7-硝基吲唑(3-Br 7-NI)和可溶性鸟苷酸环化酶(sGC)的高选择性、不可逆抑制剂[1H-[1,2,4]-恶二唑[4,3a]-喹喔啉-1-酮](ODQ)对大鼠工作记忆和参考记忆以及情绪学习的影响。

主要方法

分别在三面板跑道和下楼梯式被动回避任务中评估这些效果。

主要发现

3-Br 7-NI(5、10 和 20mg/kg)和 ODQ(5、10 和 20mg/kg)显著增加了大鼠工作记忆和参考记忆表现的错误次数和潜伏期,并损害了被动回避任务的记忆保留。l-精氨酸(250mg/kg)可逆转 3-Br 7-NI 的作用。

意义

研究结果支持了这样一种假设,即 nNOS 抑制通过损害用于解决学习任务的策略,破坏参考记忆和工作记忆过程,根据这些结果,nNOS-sGC 可能是情绪学习以及参考记忆和工作记忆所必需的。

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