TY - JOUR

T1 - Chronic Behavioral and Neurochemical Effects of Four Novel N-Benzyl-2-phenylethylamine Derivatives Recently Identified as “Psychoactive” in Adult Zebrafish Screens

AU - Ilyin, Nikita

AU - Nabiullin, Arslan D.

AU - Kozlova, Anna D.

AU - Kupriyanova, Olga

AU - Shevyrin, Vadim

AU - Gloriozova, Tatyana

AU - Filimonov, Dmitry

AU - Lagunin, Alexey

AU - Galstyan, David

AU - Kolesnikova, Tatiana

AU - Mor, Mikael

AU - Efimova, Evgeniya

AU - Poroikov, Vladimir

AU - Yenkoyan, Konstantin b.

AU - De Abreu, Murilo

AU - Demin, Konstantin a.

AU - Kalueff, Allan

N1 - T.O.K. was supported by the Sirius University of Science and Technology. O.V.K. is supported by the subsidy allocated to the Kazan Federal University for the state research assignment in the sphere of scientific activities (#FZSM-2023-0013). V.A.S. was supported by the Ministry of Science and Higher Education of the Russian Federation within the Development Program of Ural Federal University in accordance with the program of strategic academic leadership \u201CPrioritet-2030\u201D. In silico estimations were obtained in the framework of the Program for Basic Research in the Russian Federation for a long-term period (2021-2030) (no. 122030100170-5). A.V.K. was supported by Suzhou Key Laboratory on Neurobiology and Cell Signaling (XJTLU). N.P.I. and D.S.G. are supported by St. Petersburg State University funds. Текст о финансировании #2 This work was financially supported by the Ministry of Science and Higher Education of the Russian Federation (agreement no. 075-15-2020-901). The funders had no role in the design, analyses, and interpretation of the submitted study or decision to publish.

PY - 2024/5/15

Y1 - 2024/5/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?partnerID=8YFLogxK&scp=85192154112

U2 - 10.1021/acschemneuro.4c00017

DO - 10.1021/acschemneuro.4c00017

M3 - Article

VL - 15

SP - 2006

EP - 2017

JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

SN - 1948-7193

IS - 10

ER -