Abstract：
Potently affecting human and animal brain and behavior, hallucinogenic drugs have recently emerged as potentially promising agents in psychopharmacotherapy. Complementing laboratory rodents, the zebrafish (Danio rerio) is a powerful model organism for screening neuroactive drugs, including hallucinogens. Here, we tested four novel N-benzyl-2-phenylethylamine (NBPEA) derivatives with 2,4- and 3,4-dimethoxy substitutions in the phenethylamine moiety and the -F, -Cl, and -OCF3 substitutions in the ortho position of the phenyl ring of the N-benzyl moiety (34H-NBF, 34H-NBCl, 24H-NBOMe(F), and 34H-NBOMe(F)), assessing their behavioral and neurochemical effects following chronic 14 day treatment in adult zebrafish. While the novel tank test behavioral data indicate anxiolytic-like effects of 24H-NBOMe(F) and 34H-NBOMe(F), neurochemical analyses reveal reduced brain norepinephrine by all four drugs, and (except 34H-NBCl) - reduced dopamine and serotonin levels. We also found reduced turnover rates for all three brain monoamines but unaltered levels of their respective metabolites. Collectively, these findings further our understanding of complex central behavioral and neurochemical effects of chronically administered novel NBPEAs and highlight the potential of zebrafish as a model for preclinical screening of small psychoactive molecules.
摘要：
强烈影响人类和动物的大脑和行为，致幻药物最近已成为精神药物治疗中潜在的有前途的药物。补充实验室啮齿动物，斑马鱼（Daniorerio）是筛选神经活性药物的强大模型生物，包括致幻剂.这里,我们测试了四种在苯乙胺部分和-F中具有2,4-和3,4-二甲氧基取代的新型N-苄基-2-苯乙胺（NBPEA）衍生物，-Cl,和N-苄基部分的苯环的邻位中的-OCF3取代（34H-NBF，34H-NBCl,24H-NBOMe(F),和34H-NBOMe（F）），评估成年斑马鱼慢性治疗14天后的行为和神经化学效应。虽然新的坦克测试行为数据表明24H-NBOMe（F）和34H-NBOMe（F）的抗焦虑作用，神经化学分析显示所有四种药物都减少了大脑去甲肾上腺素，和（34H-NBCl除外）-降低多巴胺和5-羟色胺水平。我们还发现，所有三种脑单胺的周转率均降低，但其各自代谢物的水平未改变。总的来说，这些发现进一步加深了我们对慢性给药的新型NBPEAs的复杂中枢行为和神经化学效应的理解,并突出了斑马鱼作为小精神活性分子临床前筛查模型的潜力.
