Effects Of The Synthetic Cannabinoid MDMB-4en-PINACA On Zebrafish Behavior And Metabolomic Alterations Associated With Neurotransmitter Systems

Objective: This study was performed to evaluate the behavioral alterations of in male zebrafish of acute exposure MDMB-4en-PINACA.The current study utilized targeted metabolomics analysis of neurotransmitters and related compounds to assess the influence of acute exposures to different doses of MDMB-4en-PINACA on neuro-transmitter systems.Methods: In this experiment,six intervention groups at concentration doses equal to 25、50、75、125、250、500 μg/kg,and a vehicle control group(0.4% DMSO)were used.MDMB-4en-PINACA was injected intraperitoneally.Zebrafish were acutely exposed to MDMB-4en-PINACA for 15 min and their locomotion,exploratory activity,and aggression towards mirror were further assessed.Thus,the present study was undertaken with the aim of its influence on the targeted metabolomics profile associated with neurotransmission in zebrafish brain.Results:1.As compared to vehicle,the zebrafish locomotion did not change after acute exposure,MDMB-4en-PINACA increased circling behavior.2.In the novel tank test,ANOVA revealed a significant drug effect on time spent in top,number of entries to top,but not distance traveled,velocity,acceleration,angular velocity,turn angle.3.MDMB-4en-PINACA(25μg/kg)increased aggression-related phenotypes.While 75-500μg/kg reduced aggression and hyperlocomotion.4.Acute MDMB-4en-PINACA exposures induced metabolomic alterations associated with the neurotransmitter systems,and the 5-hydroxytryptamine pathway,the dopaminergic pathway,the cholinergic pathway,the histaminergic pathway.Conclusions:1.Taken together,these results indicate that MDMB-4en-PINACA,exhibits unique and potent effects,independently from its motor activity,suggesting the usefulness of the zebrafish model to study aggression and hallucinatory behavior.2.These effects appear mediated by activation of cannabinoid CB1 receptors.