Behavioral and neurochemical effects of novel N-Benzyl-2-phenylethylamine derivatives in adult zebrafish
bioRxiv (Cold Spring Harbor Laboratory) January 21, 2022 Konstantin A. Demin, Olga V. Kupriyanova, Вадим А. Шевырин et al. preprint
Certain synthetic N-Benzyl-2-phenylethylamine (NBPEA) derivatives, related to hallucinogens like mescaline and MDMA, produce distinct behavioral and neurochemical effects in adult zebrafish. Substitutions on the N-benzyl fragment primarily affected locomotion, while those on the phenethylamine moiety influenced anxiety-like behavior. The compounds also modulated brain serotonin and/or dopamine turnover. Several behavioral clusters emerged: anxiogenic/hypolocomotor, behaviorally inert, anxiogenic/hallucinogenic-like, and anxiolytic/hallucinogenic-like. Two compounds reduced despair-like behavior. Artificial intelligence-driven phenotyping linked multiple compounds to NMDA antagonists and/or MDMA, suggesting hallucinogenic-like properties. In silico modeling indicated similarities between these NBPEAs, MDMA, and ketamine, implicating serotonin release, calcium channel activity, and serotonin receptor involvement.