Effects of New Psychoactive Substance Esketamine on Behaviors and Transcription of Genes in Dopamine and GABA Pathways in Zebrafish Larvae.

Esketamine (ESK), the S-enantiomer of ketamine, alters behaviors and gene transcription in zebrafish larvae at environmentally relevant concentrations. At 12.4 ng L⁻¹, ESK reduced touch response at 48 hours post-fertilization and decreased swimming time and distance in the outer zone during light periods, suggesting reduced anxiety. ESK also increased transcription of dopamine pathway genes (th, ddc, drd1a, drd3, drd4a) and GABA pathway genes (slc6a1b, slc6a13, slc12a2). These results indicate that ESK can cause neurotoxicity in early-stage zebrafish by affecting heart rate, behaviors, and gene expression in dopamine and GABA pathways.

Study at a glance

Abstract

Esketamine (ESK) is the S-enantiomer of ketamine racemate (a new psychoactive substance) that can result in illusions, and alter hearing, vision, and proprioception in human and mouse. Up to now, the neurotoxicity caused by ESK at environmental level in fish is still unclear. This work studied the effects of ESK on behaviors and transcriptions of genes in dopamine and GABA pathways in zebrafish larvae at ranging from 12.4 ng L- 1 to 11141.1 ng L- 1 for 7 days post fertilization (dpf). The results showed that ESK at 12.4 ng L- 1 significantly reduced the touch response of the larvae at 48 hpf. ESK at 12.4 ng L- 1 also reduced the time and distance of larvae swimming at the outer zone during light period, which implied that ESK might potentially decrease the anxiety level of larvae. In addition, ESK increased the transcription of th, ddc, drd1a, drd3 and drd4a in dopamine pathway. Similarly, ESK raised the transcription of slc6a1b, slc6a13 and slc12a2 in GABA pathway. This study suggested that ESK could affect the heart rate and behaviors accompanying with transcriptional alterations of genes in DA and GABA pathways at early-staged zebrafish, which resulted in neurotoxicity in zebrafish larvae.