Zebrafish: The Aquatic Pioneers of Brain Research

Zebrafish (Danio rerio) have emerged as a pivotal model organism in translational neuroscience, neuropharmacology and CNS disorder research, leveraging their striking anatomical and physiological parallels to humans. With a brain architecture and functional pathways that are closely similar to those of humans, zebrafish enable critical insights into brain development, neuro-circuitry and disease mechanisms. Notably, zebrafish have a number of benefits over more conventional mammalian models like mice and rats, including their rapid development, optical transparency allowing for real-time imaging and capacity to perform high-throughput genetic and pharmacological screens inexpensively. The combination of vertebrate complexity and experimental tractability that zebrafish possesses renders them uniquely placed for large-scale investigations of brain function and disease. This review synthesizes recent advancements in utilizing zebrafish to model brain disorders such as depression, anxiety, psychoses, autism spectrum disorders, cognitive impairments and drug-induced neurobehavioural alterations. By integrating findings from genetic, pharmacological and behavioural studies, we underscore zebrafish's unique advantages, including genetic tractability, cost-efficiency, high-throughput screening capacity and conserved neuroendocrine and behavioural responses. These features facilitate the exploration of complex neuropsychological processes and drug-brain interactions, bridging gaps between molecular mechanisms and behavioural outcomes. Zebrafish models have proven instrumental in unravelling the neurobiological underpinnings of human psychiatric and neurological disorders, offering a versatile platform for studying gene-environment interactions, neurodevelopmental trajectories and pharmacological interventions. Their translational relevance is further enhanced by rapid developmental cycles, optical transparency during early stages and robust behavioural assays that capture nuanced phenotypes. This review highlights the transformative role of zebrafish in accelerating drug discovery, optimizing neuropharmacological screening and advancing personalized therapeutic strategies. By consolidating evidence from diverse studies, we highlight zebrafish's capacity to address fundamental questions in neuroscience while fostering innovative approaches to diagnose, treat and prevent brain disorders, ultimately driving progress towards precision medicine in neurology and psychiatry.