Pathophysiological impacts of 5-MeO-MiPT on zebrafish (Danio rerio) via the Gαq/11-PLCβ signaling pathway
Sen Zhao, Meng Liu, Jinyuan Chen, Liang Meng, Yanjiao Wang
Ecotoxicology and Environmental Safety August 30, 2024 DOI: 10.1016/j.ecoenv.2024.116969 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Zebrafish |
| Intervention | 5-MeO-MiPT |
| Dose | varying concentrations |
| Duration | 30 days |
| Topics | 5-MeO-DMT |
| Keywords | Zebrafish Danio Oxidative stress Gene expression Pharmacology Tryptamines Transcription factor Cell biology Toxicology Biochemistry |
| Citations | 1 |
| Key findings | 5-MeO-MiPT alters expression of 13 genes and modulates multiple signaling pathways (inhibiting DAG-Ca2+/Pkc/Erk, Pkc/Pla2/PLCs, Ca2+/CamkII/NMDA and enhancing Ca2+/Creb) via the Gα q/11-PLCβ pathway, mediating behavioral inhibition and oxidative stress in zebrafish. |
Abstract
Novel Psychoactive Substances (NPS) derived from tryptamines has been detected in aquatic environments, leading to environmental toxicology concerns. However, the specific toxicological mechanism, underlying these NPS, remains unclear. In our previous work, we used 5-Methoxy-N-isopropyl-N-methyltryptamine (5-MeO-MiPT) as the representative drug for NPS, and found that, 5-MeO-MiPT led to obvious behavioral inhibition and oxidative stress responses in zebrafishes model. In this study, Zebrafish were injected with varying concentrations of 5-MeO-MiPT for 30 days. RNA-seq, qPCR, metabolomics, and histopathological analyses were conducted to assess gene expression and tissue integrity. This study confirms that 5-MeO-MiPT substantially influences the transcription and expression of 13 selected genes, including ucp1 , pet100 , grik3 , and grik4 , mediated by the Gα q/11 -PLC β signaling pathway. We elucidate the molecular mechanism that 5-MeO-MiPT can inhibit DAG-Ca 2+ /Pkc/Erk, Pkc/Pla2/PLCs and Ca 2+ /Camk Ⅱ/NMDA, while enhance Ca 2+ /Creb. Those secondary signaling pathways may be the mechanisms mediating 5-MeO-MiPT inhibiting normal behavior in zebrafish. These findings offer novel insights into the toxicological effects and addiction mechanisms of 5-MeO-MiPT. Moreover, it presents promising avenues for investigating other tryptamine-based NPS and offers a new direction for diagnosing and treating liver-brain pathway-related diseases. • The study investigated 5-MeO-MiPT's impact on zebrafish. • It caused oxidative stress and behavioral inhibition. • RNA-seq and qPCR analyses revealed gene expression changes. • Gα q/11 -PLC β signaling mediated these effects.
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
Cites 7
- Serotonin, But Not N -Methyltryptamines, Activates the Serotonin 2A Receptor Via a β-Arrestin2/Src/Akt Signaling Complex In Vivo Journal of Neuroscience October 6, 2010
- Active Metabolite of Aeruginascin (4-Hydroxy-N,N,N-trimethyltryptamine): Synthesis, Structure, and Serotonergic Binding Affinity ACS Omega July 2, 2020
- Study of the in vitro and in vivo metabolism of the tryptamine 5‐MeO‐MiPT using human liver microsomes and real case samples Drug Testing and Analysis July 5, 2017
- New Psychoactive Substance 5-MeO-MiPT In vivo Acute Toxicity and Hystotoxicological Study. Balkan Medical Journal 2021
- Pharmaco-toxicological effects of the novel tryptamine hallucinogen 5-MeO-MiPT on motor, sensorimotor, physiological, and cardiorespiratory parameters in mice-from a human poisoning case to the preclinical evidence. Psychopharmacology March 1, 2024
and 2 more in the library