Effects of Short‐Term 5‐MeO‐DiPT Exposure on the Brain Metabolome of Zebrafish ( Danio rerio )

Abstract

5-MeO-DiPT (5-methoxy-N,N-diisopropyltryptamine) has been preliminarily reported to exhibit short-term hallucinogenic effects on humans. However, the connection between its toxic mechanism and behavioral changes remains unexplored. Therefore, this study used zebrafish as the research subject to investigate the metabolic characteristics of 5-MeO-DiPT and its perturbation effects on the metabolic network of organisms and verified the specific impacts of this perturbation through behavioral studies. It is shown that 27 metabolites with significant changes were detected in the brain of zebrafish after being exposed to 5-MeO-DiPT for a short period. The concentration of eight metabolites is increased, whereas the other 19 show a downward trend. Additionally, nine core metabolic pathways were significantly perturbed (p < 0.05). It is indicated that 5-MeO-DiPT disrupted the homeostasis of neurotransmitters, interfered with amino acid metabolism and lipid peroxidation reactions, causing a series of damages to the organism's neural conduction, immune response, and energy metabolism. Its potential carcinogenic risk and the mechanism of inducing metabolic syndrome deserve attention. Filling the theoretical gap in the research of the metabolic mechanism of this drug provides a reference basis for the next step of its research direction.