Nontargeted metabolomic insights into the behavioral effects of 5-MeO-MiPT in zebrafish (Danio rerio)

5-MeO-MiPT, a novel psychoactive tryptamine, caused inhibited movement and anxiety-like behavior in adult zebrafish. Metabolomic analysis after drug injection revealed 22 distinct potential biomarkers and seven significantly altered metabolic pathways, including amino acid, lipid, and energy metabolism. The metabolic changes indicated observable brain damage, especially disruption in the liver-brain pathway, linking the drug's metabolic effects to the anxiety-like behavior.

Study at a glance

Abstract

5-Methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MiPT) is a novel psychoactive substance exhibiting a tryptamine structure. Despite its increasing prevalence, the environmental impact of 5-MeO-MiPT remains unexplored. Our prior investigation revealed that 5-MeO-MiPT induced inhibited spontaneous movement and prompted anxiety-like behavior in adult zebrafish-a validated toxicological model. To elucidate this phenomenon and establish a correlation between metabolomics and behavioral changes induced by 5-MeO-MiPT, zebrafish were administered varying drug concentrations. Zebrafishes were subjected to injections of different 5-MeO-MiPT concentrations. Subsequent metabolomic analysis of endogenous metabolites affected by the drug unveiled substantial variations in metabolic levels between the control group and the drug-injected cohorts. A total of 22 distinct metabolites emerged as potential biomarkers. Further scrutiny identified seven pathways significantly influenced by 5-MeO-MiPT. A focused exploration into amino acid metabolism, lipid metabolism, and energy metabolism unveiled that the metabolic repercussions of 5-MeO-MiPT on zebrafish resulted in observable brain damage. Notably, the study identified a consequential disruption in the liver-brain pathway. The comprehensive metabolomic approach employed herein effectively discerned the impact of 5-MeO-MiPT on zebrafish metabolism. This approach also shed light on the mechanism underpinning the anxiety-like behavior observed in zebrafish post-drug injection. Specifically, our findings indicate that 5-MeO-MiPT induces brain damage, particularly within the liver-brain pathway.