Role of neuronal nicotinic acetylcholine receptors (nAChRs) on learning and memory in zebrafish
Role of neuronal nicotinic acetylcholine receptors (nAChRs) on learning and memory in zebrafish
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DOI：
10.1007/s00213-013-3340-1
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发表时间：
2014-05-01
影响因子：
3.4
通讯作者：
Sala, Mariaelvina
中科院分区：
文献类型：
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作者：
Braida, Daniela;Ponzoni, Luisa;Sala, Mariaelvina
神经元烟碱乙酰胆碱受体（nAChRs）在认知中起调节作用，斑马鱼为研究学习和记忆提供了临床前模型。通过t型迷宫实验，研究了烟碱（NIC）和部分激动剂（CC4和CC26）对斑马鱼空间记忆的影响。使用选择性nAChR拮抗剂评估α 4/ α 6 β 2和α 7 nAChR在nic诱导的记忆增强中的作用。低剂量和高剂量NIC、cytisine （CYT）、CC4和CC26分别改善和恶化了平均运行时间，呈倒U型剂量-响应函数。有效剂量（ED50） （x10(-5) mg/kg） CC4为0.4，CYT为4.5，NIC为140，CC26为200。选择性nAChR亚型拮抗剂：α 7的甲基lycaaconitine (MLA)， α 6 β 2的α -conotoxin (MII)， α 4 β 2的二氢- β -erythroidine (Dh β E)，非选择性拮抗剂mecamylamine （MEC）和毒蕈碱拮抗剂东莨菪碱（SCOP），其中Dh β E比MLA或MII更有活性。所有的部分激动剂都阻断了认知增强。每一种部分激动剂的最大有效剂量的改善被低剂量的Dh β E （0.001 mg/kg）和MII （0.01 mg/kg）阻断。MLA分别在0.01 mg/kg和1 mg/kg剂量下降低CC26和CC4的作用，但在任何测试剂量下都不能拮抗cyt诱导的记忆改善。没有观察到游泳活动的变化。我们的研究结果表明，斑马鱼为快速筛选新的α 4 β 2 nAChR化合物对空间记忆的影响提供了一个有用的模型。
Neuronal nicotinic acetylcholine receptors (nAChRs) play a modulatory role in cognition, and zebrafish provide a preclinical model to study learning and memory.We investigated the effect of nicotine (NIC) and some new cytisine-derived partial agonists (CC4 and CC26) on spatial memory in zebrafish using a rapid assay on T-maze task. The role of alpha 4/alpha 6 beta 2 and the alpha 7 nAChRs in NIC-induced memory enhancement was evaluated using selective nAChR antagonists.Low and high doses of NIC, cytisine (CYT), CC4 and CC26 respectively improved and worsened the mean running time, showing an inverted U dose-response function. The effective dose (ED50) (x10(-5) mg/kg) was 0.4 for CC4, 4.5 for CYT, 140 for NIC and 200 for CC26. NIC-induced cognitive enhancement was reduced by the selective nAChR subtype antagonists: methyllycaconitine (MLA) for alpha 7, alpha-conotoxin (MII) for alpha 6 beta 2, dihydro-beta-erythroidine (Dh beta E) for alpha 4 beta 2, the nonselective antagonist mecamylamine (MEC) and the muscarinic antagonist scopolamine (SCOP), with Dh beta E being more active than MLA or MII. All the partial agonists blocked the cognitive enhancement. The improvement with the maximal active dose of each partial agonist was blocked by low doses of Dh beta E (0.001 mg/kg) and MII (0.01 mg/kg). MLA reduced the effects of CC26 and CC4 at doses of 0.01 and 1 mg/kg, respectively, but did not antagonize CYT-induced memory improvement at any of the tested dose. No change in swimming activity was observed.Our findings demonstrate that zebrafish make a useful model for the rapid screening of the effect of new alpha 4 beta 2 nAChR compounds on spatial memory.