Esketamine Exposure Affects Neurodevelopment and Glutamate-NMDAR Signaling in Zebrafish Larvae.

Abstract

Esketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has become a preferred option for perioperative use in infants and young children with low compliance due to its rapid onset and convenient administration. However, concerns regarding its potential neurotoxic effects during development warrant further investigation. This study aimed to elucidate the impact of esketamine on neurodevelopment and function in zebrafish larvae. Five days post-fertilization (dpf) zebrafish larvae were exposed to esketamine at concentrations of 10 mg/L and 100 mg/L for 2 and 6 h. The results demonstrated that esketamine exposure induced hyperlocomotion and increased dark preference in the larvae. Additionally, it elevated glutamate levels and significantly altered the expression of genes related to NMDAR and neurodevelopment. N-methyl-D-aspartate (NMDA) is an agonist of the NMDAR that reverses esketamine-induced hyperactivity and manf overexpression. In conclusion, esketamine exerts discernible effects on neurodevelopment and function in zebrafish larvae, with glutamatergic signaling potentially serving as a key underlying mechanism. These findings provide novel insights into the potential effects of clinical use of esketamine in pediatric populations, facilitating its safer application.

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