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利多卡因外周和全身给药后对成年斑马鱼行为及脑乙酰胆碱酯酶的影响。

Effects of lidocaine on adult zebrafish behavior and brain acetylcholinesterase following peripheral and systemic administration.

作者信息

de Abreu Murilo S, Giacomini Ana C V V, Dos Santos Bruna E, Genario Rafael, Marchiori Natalia I, Rosa Larissa G da, Kalueff Allan V

机构信息

Bioscience Institute, University of Passo Fundo (UPF), Passo Fundo, RS, Brazil; The International Zebrafish Neuroscience Research Consortium (ZNRC), Slidell, LA, USA.

Bioscience Institute, University of Passo Fundo (UPF), Passo Fundo, RS, Brazil; Postgraduate Program in Environmental Sciences, University of Passo Fundo (UPF), Passo Fundo, Brazil.

出版信息

Neurosci Lett. 2019 Jan 23;692:181-186. doi: 10.1016/j.neulet.2018.11.004. Epub 2018 Nov 3.

DOI:10.1016/j.neulet.2018.11.004
PMID:30399397
Abstract

Lidocaine is a voltage-gated Na channel blocker, commonly used as a fast-acting local and general anesthetic. Lidocaine also has central action, affecting behavior both clinically and in animal models. Adult zebrafish are rapidly becoming a critical novel model organism in translational neuroscience research. Here, we examine the effects of acute peripheral (lateral line application, 4%) and systemic (water immersion, 1, 5 and 10 mg/L) administration of lidocaine on adult zebrafish behavior tested in the novel tank test. Overall, the drug evoked hypolocomotor effect when applied systemically (at 10 mg/L) and peripherally. Peripheral lidocaine also reduced top exploration in the novel tank test (vs. sham), suggesting anxiogenic-like effect of the lateral line blockage, Our findings show the importance of the lateral line system in driving adult zebrafish locomotion, and suggest sedative-like effects of systemic lidocaine in aduld zebrafish. In addition, reflecting the role of central cholinergic contribution in lidocaine action, brain acetylcholinesterase (AChE) activity was lower following peripheral and systemic administration of lidocaine at behaviorally active doses. Collectively, our data support the effects of lidocaine on behavioral responses in zebrafish, and reinforce the growing utility of this aquatic model to screen various CNS drugs.

摘要

利多卡因是一种电压门控钠通道阻滞剂,常用作速效局部和全身麻醉剂。利多卡因也具有中枢作用,在临床和动物模型中均会影响行为。成年斑马鱼正迅速成为转化神经科学研究中一种关键的新型模式生物。在此,我们研究了急性外周(侧线给药,4%)和全身(水浸,1、5和10 mg/L)给予利多卡因对成年斑马鱼在新鱼缸试验中行为的影响。总体而言,全身(10 mg/L)和外周给药时,该药物会诱发运动减少效应。外周利多卡因还减少了新鱼缸试验中的顶部探索(与假手术组相比),提示侧线阻断具有类焦虑样效应。我们的研究结果表明侧线系统在驱动成年斑马鱼运动中的重要性,并提示全身利多卡因对成年斑马鱼具有类镇静作用。此外,反映中枢胆碱能在利多卡因作用中的贡献,在行为活跃剂量下外周和全身给予利多卡因后,脑乙酰胆碱酯酶(AChE)活性降低。总体而言,我们的数据支持利多卡因对斑马鱼行为反应的影响,并强化了这种水生模型在筛选各种中枢神经系统药物方面日益增长的实用性。

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