Chapter 36 - Use of zebrafish embryos to study molecular and cellular neurotoxic effects of drugs: A focus on signaling and ketamine

Abstract

Ketamine, a phencyclidine derivative, and a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) receptor, is a pediatric anesthetic. Studies have shown that ketamine exposure during early development can be neurotoxic in zebrafish, rodents, and nonhuman primates. Despite many reports showing ketamine-induced neurotoxicity in mammals, reversal of the adverse effects through intervention of cell signaling pathways that could reveal relevant mechanisms of such toxicities remains scarce. Lately, zebrafish embryos have become an attractive model for chemical-induced toxicity assays and for conducting mechanistic studies that reveal signaling/molecular pathways involved, often in vivo. Since the signaling pathways and genetic makeup are conserved between mammals and zebrafish, the predictive capability of the zebrafish embryo model, with respect to drug effects, fares well in revealing the cellular and molecular mechanisms. This chapter provides a brief review of such mechanisms potentially involved in ketamine-induced neurotoxicity based on zebrafish embryo research.