Postgraduate Program in Environmental Sciences, University of Passo Fundo, Passo Fundo, Brazil.
Bioscience Institute, University of Passo Fundo, Passo Fundo, Brazil.
J Psychopharmacol. 2020 Dec;34(12):1449-1456. doi: 10.1177/0269881120944155. Epub 2020 Aug 27.
A potent acetylcholinesterase inhibitor, donepezil is a cognitive enhancer clinically used to treat neurodegenerative diseases. However, its complete pharmacological profile beyond cognition remains unclear. The zebrafish () is rapidly becoming a powerful novel model organism in neuroscience and central nervous system drug screening.
Here, we characterize the effects of 24-h donepezil administration on anxiety-like behavioral and endocrine responses in adult zebrafish.
We evaluated zebrafish anxiety-like behaviors in the novel tank, the light-dark and the shoaling tests, paralleled by assessing brain acetylcholinesterase activity and whole-body cortisol levels.
Overall, donepezil dose-dependently decreased zebrafish locomotor activity in the novel tank test and reduced time in light in the light-dark test, likely representing hypolocomotion and anxiety-like behaviors. Donepezil predictably decreased brain acetylcholinesterase activity, also increasing whole-body cortisol levels, thus further linking acetylcholinesterase inhibition to anxiety-like behavioral and endocrine responses.
Collectively, these findings suggest negative modulation of zebrafish affective behavior by donepezil, support the key role of cholinergic mechanisms in behavioral regulation in zebrafish, and reinforce the growing utility of zebrafish models for studying complex behavioral processess and their neuroendocrine and neurochemical regulation.
多奈哌齐是一种强效乙酰胆碱酯酶抑制剂，作为认知增强剂被临床用于治疗神经退行性疾病。然而，其在认知以外的完整药理学特征尚不清楚。斑马鱼（）正在迅速成为神经科学和中枢神经系统药物筛选的强大新型模式生物。
本研究旨在描述 24 小时多奈哌齐给药对成年斑马鱼焦虑样行为和内分泌反应的影响。
我们在新颖的水箱、明暗和群居测试中评估了斑马鱼的焦虑样行为，同时评估了大脑乙酰胆碱酯酶活性和全身皮质醇水平。
多奈哌齐呈剂量依赖性地降低了新颖水箱测试中斑马鱼的运动活动，并减少了明暗测试中在亮区的时间，可能代表运动活动减少和焦虑样行为。多奈哌齐可预测地降低了大脑乙酰胆碱酯酶的活性，同时增加了全身皮质醇水平，因此进一步将乙酰胆碱酯酶抑制与焦虑样行为和内分泌反应联系起来。
总的来说，这些发现表明多奈哌齐对斑马鱼情感行为的负向调节，支持了胆碱能机制在斑马鱼行为调节中的关键作用，并增强了斑马鱼模型在研究复杂行为过程及其神经内分泌和神经化学调节方面的日益应用。
