Nikita P. Ilyin, Arslan D. Nabiullin, Anna D. Kozlova, Olga V. Kupriyanova, Vadim A. Shevyrin, Tatyana Gloriozova, Dmitry Filimonov, Alexey Lagunin, David S. Galstyan, Tatiana O. Kolesnikova, Mikael S. Mor, Evgeniya V. Efimova, Vladimir Poroikov, Konstantin B. Yenkoyan, Murilo S. de Abreu, Konstantin A. Demin* and Allan V. Kalueff*,
{"title":"最近在成年斑马鱼筛选中被鉴定为具有 \"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效应","authors":"Nikita P. Ilyin, Arslan D. Nabiullin, Anna D. Kozlova, Olga V. Kupriyanova, Vadim A. Shevyrin, Tatyana Gloriozova, Dmitry Filimonov, Alexey Lagunin, David S. Galstyan, Tatiana O. Kolesnikova, Mikael S. Mor, Evgeniya V. Efimova, Vladimir Poroikov, Konstantin B. Yenkoyan, Murilo S. de Abreu, Konstantin A. Demin* and Allan V. Kalueff*, ","doi":"10.1021/acschemneuro.4c00017","DOIUrl":null,"url":null,"abstract":"<p >Potently affecting human and animal brain and behavior, hallucinogenic drugs have recently emerged as potentially promising agents in psychopharmacotherapy. Complementing laboratory rodents, the zebrafish (<i>Danio rerio</i>) is a powerful model organism for screening neuroactive drugs, including hallucinogens. Here, we tested four novel <i>N</i>-benzyl-2-phenylethylamine (NBPEA) derivatives with 2,4- and 3,4-dimethoxy substitutions in the phenethylamine moiety and the −F, −Cl, and −OCF<sub>3</sub> substitutions in the <i>ortho</i> position of the phenyl ring of the <i>N</i>-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.</p>","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":null,"pages":null},"PeriodicalIF":4.1000,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Chronic Behavioral and Neurochemical Effects of Four Novel N-Benzyl-2-phenylethylamine Derivatives Recently Identified as “Psychoactive” in Adult Zebrafish Screens\",\"authors\":\"Nikita P. Ilyin, Arslan D. Nabiullin, Anna D. Kozlova, Olga V. Kupriyanova, Vadim A. Shevyrin, Tatyana Gloriozova, Dmitry Filimonov, Alexey Lagunin, David S. Galstyan, Tatiana O. Kolesnikova, Mikael S. Mor, Evgeniya V. Efimova, Vladimir Poroikov, Konstantin B. Yenkoyan, Murilo S. de Abreu, Konstantin A. Demin* and Allan V. Kalueff*, \",\"doi\":\"10.1021/acschemneuro.4c00017\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Potently affecting human and animal brain and behavior, hallucinogenic drugs have recently emerged as potentially promising agents in psychopharmacotherapy. Complementing laboratory rodents, the zebrafish (<i>Danio rerio</i>) is a powerful model organism for screening neuroactive drugs, including hallucinogens. Here, we tested four novel <i>N</i>-benzyl-2-phenylethylamine (NBPEA) derivatives with 2,4- and 3,4-dimethoxy substitutions in the phenethylamine moiety and the −F, −Cl, and −OCF<sub>3</sub> substitutions in the <i>ortho</i> position of the phenyl ring of the <i>N</i>-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.</p>\",\"PeriodicalId\":13,\"journal\":{\"name\":\"ACS Chemical Neuroscience\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2024-04-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Chemical Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acschemneuro.4c00017\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Chemical Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acschemneuro.4c00017","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Chronic Behavioral and Neurochemical Effects of Four Novel N-Benzyl-2-phenylethylamine Derivatives Recently Identified as “Psychoactive” in Adult Zebrafish Screens
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.
期刊介绍:
ACS Chemical Neuroscience publishes high-quality research articles and reviews that showcase chemical, quantitative biological, biophysical and bioengineering approaches to the understanding of the nervous system and to the development of new treatments for neurological disorders. Research in the journal focuses on aspects of chemical neurobiology and bio-neurochemistry such as the following:
Neurotransmitters and receptors
Neuropharmaceuticals and therapeutics
Neural development—Plasticity, and degeneration
Chemical, physical, and computational methods in neuroscience
Neuronal diseases—basis, detection, and treatment
Mechanism of aging, learning, memory and behavior
Pain and sensory processing
Neurotoxins
Neuroscience-inspired bioengineering
Development of methods in chemical neurobiology
Neuroimaging agents and technologies
Animal models for central nervous system diseases
Behavioral research