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致幻剂阿托品和东莨菪碱对成年斑马鱼的急性行为影响。

Acute behavioral effects of deliriant hallucinogens atropine and scopolamine in adult zebrafish.

作者信息

Volgin Andrey D, Yakovlev Oleg A, Demin Konstantin A, Alekseeva Polina A, Kalueff Allan V

机构信息

Almazov National Medical Research Centre, Ministry of Healthcare of Russian Federation, St. Petersburg, Russia; Institute of Translational Biomedicine (ITBM), St. Petersburg State University, St. Petersburg, Russia; Military Medical Academy, St Petersburg, Russia.

Almazov National Medical Research Centre, Ministry of Healthcare of Russian Federation, St. Petersburg, Russia.

出版信息

Behav Brain Res. 2019 Feb 1;359:274-280. doi: 10.1016/j.bbr.2018.10.033. Epub 2018 Oct 23.

Abstract

Atropine and scopolamine are classical muscarinic cholinergic antagonists that exert multiple CNS effects. Belonging to a group of deliriant hallucinogens, these drugs induce delirium-like hallucinations, hyperactivity, altered affective states and amnesia. However, as deliriants remain the least studied group of hallucinogens, their complex and poorly understood profiles necessitate further clinical and preclinical studies. The zebrafish (Danio rerio) is rapidly emerging as a powerful model organism for translational neuropsychopharmacology research. Here, we characterize acute behavioral effects of atropine (60, 90 and 120 mg/L) and scopolamine (60, 120, 180 and 240 mg/L) in adult zebrafish subjected to the novel tank (NTT), light-dark (LDT) and shoaling tests. Overall, atropine at 90 mg/L only mildly increased the NTT locomotor activity, scopolamine at 120 mg/L produced anxiogenic-like NTT effects without affecting other behaviors, and both drugs similarly disrupted zebrafish group behavior in the shoaling test. Collectively, this supports complex and partially overlapping deliriant-like effects of acute atropine and scopolamine in zebrafish. The behavioral sensitivity to these drugs suggests zebrafish as potential screens for cholinergic deliriant psychotropic agents, also necessitating further cross-species in-vivo experimental studies.

摘要

阿托品和东莨菪碱是经典的毒蕈碱胆碱能拮抗剂,可产生多种中枢神经系统效应。作为谵妄性致幻剂的一种,这些药物会引发类似谵妄的幻觉、多动、情感状态改变和失忆。然而,由于谵妄性致幻剂仍是研究最少的致幻剂类别,其复杂且鲜为人知的特性需要进一步的临床和临床前研究。斑马鱼(Danio rerio)正迅速成为转化神经精神药理学研究的强大模式生物。在此,我们描述了阿托品(60、90和120mg/L)和东莨菪碱(60、120、180和240mg/L)对成年斑马鱼在新水箱试验(NTT)、明暗试验(LDT)和群居试验中的急性行为影响。总体而言,90mg/L的阿托品仅轻微增加了新水箱试验中的运动活性,120mg/L的东莨菪碱产生了类似焦虑的新水箱试验效应,而不影响其他行为,并且两种药物在群居试验中同样破坏了斑马鱼的群体行为。总的来说,这支持了急性阿托品和东莨菪碱在斑马鱼中具有复杂且部分重叠的类似谵妄的效应。对这些药物的行为敏感性表明斑马鱼可作为胆碱能谵妄性精神药物的潜在筛选模型,这也需要进一步的跨物种体内实验研究。

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