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When fish take a bath: Psychopharmacological characterization of the effects of a synthetic cathinone bath salt 'flakka' on adult zebrafish.
Neurotoxicology and Teratology ( IF 2.9 ) Pub Date : 2019-02-20 , DOI: 10.1016/j.ntt.2019.02.001
Tatiana O Kolesnikova 1 , Sergey L Khatsko 1 , Oleg S Eltsov 1 , Vadim A Shevyrin 1 , Allan V Kalueff 2
Affiliation  

Alpha-pyrrolidinopentiophenone (α-PVP) is a synthetic cathinone which exerts robust mental and physiological effects clinically, as well as causes aberrant stereotypic behaviors and altered locomotion in rodents. Given the rich spectrum of pharmacological activity of α-PVP in rodents and humans, as well as its high abuse potential, further studies are needed to better understand the pharmacology and toxicology of this drug. The zebrafish (Danio rerio) is a relatively novel model organism in neuropharmacology and toxicology research. Here, we characterize behavioral effects of α-PVP in adult zebrafish following its acute (1, 5, 25 and 50 mg/L for 20 min) and chronic (1, 5 and 10 mg/L for 7 days) treatments. Overall, acute exposure to α-PVP evoked psychostimulant (but not anxiolytic-like) effects in zebrafish novel tank test, with characteristic stereotypic 'side-to-side' bottom swimming at 5, 25 and 50 mg/L. The high-performance liquid chromatography/high-resolution mass spectrometry (HPLC/HRMS) analyses of zebrafish brains showed detectable levels of α-PVP following its acute administration, likely underlying the observed behavioral effects. Although acute 2-day discontinuation of chronic 7-day α-PVP at 1, 5 and 10 mg/L produced no effects, hypolocomotion occurred after a 7-day chronic treatment and repeated withdrawal, resembling rodent effects of some chronic psychostimulants. Collectively, these findings support zebrafish sensitivity to α-PVP and show some parallels with its effects in mammals and humans. This study also suggests that aquatic models based on zebrafish can help further examine the CNS effects evoked by α-PVP and screen for related synthetic new psychoactive drugs.

中文翻译:

鱼洗澡时:合成的卡西酮浴盐“ flakka”对成年斑马鱼的影响的心理药理学表征。

α-吡咯烷基戊二酮(α-PVP)是一种合成的卡西酮,在临床上发挥强大的精神和生理作用,并引起啮齿动物的异常刻板行为和运动变化。鉴于α-PVP在啮齿动物和人类中的药理活性谱非常丰富,并且具有很高的滥用潜力,因此需要进一步研究以更好地了解这种药物的药理学和毒理学。斑马鱼(Danio rerio)是神经药理学和毒理学研究中相对较新的模型生物。在这里,我们表征了α-PVP在成年斑马鱼的急性治疗(1、5、25和50 mg / L 20分钟)和慢性治疗(1、5和10 mg / L 7天)后的行为影响。总体而言,在斑马鱼新型坦克试验中,急性暴露于α-PVP会引起精神刺激药(而非抗焦虑药)作用,具有典型的定型“左右”底部游泳,分别为5、25和50 mg / L。斑马鱼大脑的高效液相色谱/高分辨率质谱(HPLC / HRMS)分析显示,急性给药后可检测到α-PVP的水平,可能是观察到的行为影响的基础。尽管在1、5和10 mg / L的情况下,急性7天的α-PVP的急性2天停药没有作用,但经过7天的慢性治疗并反复停药后,发生了运动不足,类似于某些慢性精神兴奋药的啮齿动物作用。总的来说,这些发现支持斑马鱼对α-PVP的敏感性,并与其在哺乳动物和人类中的作用显示出一些相似之处。
更新日期:2019-11-01
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