Nontargeted metabolomic insights into the behavioral effects of 5-MeO-MiPT in zebrafish (Danio rerio)
Sen Zhao, Jinyuan Chen, Chenhao Zhong, Liang Meng, Yanjiao Wang
Ecotoxicology and Environmental Safety January 31, 2024 DOI: 10.1016/j.ecoenv.2024.116044 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled experiment Peer reviewed |
|---|---|
| Population | Adult zebrafish |
| Intervention | 5-MeO-MiPT |
| Topics | 5-MeO-DMT |
| Keywords | Zebrafish Danio Metabolomics Pharmacology Drug metabolism Metabolite Metabolic pathway Biochemistry Bioinformatics Gene |
| Citations | 3 |
| Key findings | 5-MeO-MiPT induces brain damage and disrupts the liver-brain pathway, correlating with anxiety-like behavior in zebrafish. |
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.
Comparable studies
Other preclinical and animal studies on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. Human primary monocyte-derived dendritic cells | 2014 | In vitro study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study | |
| Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Mice and rats | 2006 | Preclinical study | |
| Agonist Properties of N,N-Dimethyltryptamine at Serotonin 5-HT2A and 5-HT2C Receptors Rats and transfected fibroblasts | 1998 | Experimental study | |
| Subtypes of the 5-HT receptor mediating the behavioural responses to 5-methoxy-N,N-dimethyltryptamine in the rat Intact rats and rats depleted of monoamines with reserpine | 1985 | Experimental study |
Citations in the library
Cited by 2
Cites 3
- The hallucinogenic world of tryptamines: an updated review. Archives of Toxicology August 1, 2015
- Active Metabolite of Aeruginascin (4-Hydroxy-N,N,N-trimethyltryptamine): Synthesis, Structure, and Serotonergic Binding Affinity ACS Omega July 2, 2020
- GC-MS metabolomics reveals disturbed metabolic pathways in primary mouse hepatocytes exposed to subtoxic levels of 3,4-methylenedioxymethamphetamine (MDMA). Archives of Toxicology November 2018