Dear Editor, Zebrafish (Danio rerio), a small tropical freshwater species, has become a valuable vertebrate model in biomedical research. Recently, its use in anesthesia research has gained attention due to its unique combination of genetic similarity to humans, transparent embryonic development, and affordability. Incorporating zebrafish into anesthesia research could help connect laboratory science with clinical anesthesiology. Zebrafish share about 70% of their genes with humans, including those that regulate neural and cardiovascular functions. Their primary neurotransmitter systems—GABAergic, glutamatergic, and adrenergic—closely resemble those in mammals and are essential for mediating anesthetic effects. Additionally, because zebrafish embryos are transparent and develop outside the body, researchers can observe in real time how anesthetics affect organ development, neuronal activity, and cardiac function using advanced imaging techniques and fluorescent reporter lines.1 This model offers substantial advantages. Zebrafish provide a powerful platform for high-throughput screening of novel anesthetic agents, toxicity evaluation, and the study of developmental neurotoxicity, while involving relatively fewer ethical constraints. Commonly investigated anesthetics, including tricaine (MS-222), propofol, and isoflurane, have been assessed for their effects on behavioral suppression, recovery profiles, and physiological parameters.2 Moreover, their rapid development and remarkable regenerative capacity make zebrafish particularly valuable for examining the long-term consequences of anesthetic exposure, especially in pediatric and neurodevelopmental safety contexts Figure 1. A conceptual overview of the zebrafish model in anesthesia research is provided.Figure 1: A conceptual overview of the zebrafish model in anesthesia research. The figure illustrates the translational relevance of zebrafish for anesthetic research, highlighting genetic similarity to humans, transparent embryonic development enabling real-time imaging, assessment of cardiovascular and neurodevelopmental effects, the use of commonly studied anesthetic agents, ethical alignment with the 3Rs principles, and key advantages and challenges in experimental designHowever, several challenges remain. The pharmacokinetics of anesthetic agents vary in zebrafish due to gill-based absorption and aquatic exposure, making dose extrapolation to humans difficult. Additionally, the absence of standardized criteria for measuring “anaesthetic depth” in zebrafish hampers cross-study comparisons. Behavioral endpoints, such as loss of the startle response or righting reflex, need validation with electrophysiological data.3 Furthermore, physiological differences between larval and adult stages require the creation of stage-specific experimental protocols. To effectively incorporate zebrafish into anesthesia research, standardization is essential. Guidelines defining developmental stages, exposure durations, recovery criteria, and welfare standards should be established. Quantitative pharmacokinetic studies using analytical assays will enable more precise dose–response relationships. A collaboration among anesthesiologists, pharmacologists, and zebrafish biologists is critical for developing reliable methods and ensuring translational relevance. The ethical benefits of zebrafish research also align with the “3Rs” principles of animal testing: Replacement, Reduction, and Refinement. Early-stage embryos are exempt from many animal-use regulations, allowing researchers to study anesthesia mechanisms while reducing the need for higher-order animals.4 This model, therefore, offers an ethical and sustainable supplement to mammalian research. In conclusion, integrating zebrafish into anesthesia research offers a transformative platform for studying anesthetic pharmacology, safety, and developmental effects. With appropriate methodological rigor and interdisciplinary collaboration, the zebrafish model can strengthen preclinical evidence, promote safer anesthetic practices, and stimulate innovation in experimental anesthesiology. I hope this letter encourages more Indian institutions and researchers to explore and adopt zebrafish-based anesthesia studies within academic and translational research frameworks. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Jahangeerbasha et al. (Thu,) studied this question.