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.

中文翻译：

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最近在成年斑马鱼筛查中被鉴定为“精神活性”的四种新型 N-苄基-2-苯乙胺衍生物的慢性行为和神经化学作用


致幻药物可有效影响人类和动物的大脑和行为，最近已成为精神药物治疗中潜在有前途的药物。斑马鱼（Danio rerio）是实验室啮齿动物的补充，是筛选神经活性药物（包括致幻剂）的强大模型生物。在这里，我们测试了四种新型 N-苄基-2-苯乙胺 (NBPEA) 衍生物，其苯乙胺部分具有 2,4- 和 3,4-二甲氧基取代，并且 -F、-Cl 和 -OCF ₃ N-苄基部分苯环邻位的取代（34H-NBF、34H-NBCl、24H-NBOMe(F) 和 34H-NBOMe(F)），评估其在慢性 14 后的行为和神经化学影响成年斑马鱼的日间治疗。虽然新颖的坦克测试行为数据表明 24H-NBOMe(F) 和 34H-NBOMe(F) 具有抗焦虑样作用，但神经化学分析显示所有四种药物均减少了大脑去甲肾上腺素，并且（34H-NBCl 除外）减少了多巴胺和血清素水平。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长期服用新型 NBPEA 的复杂中枢行为和神经化学效应的理解，并强调了斑马鱼作为精神活性小分子临床前筛查模型的潜力。