Insights from zebrafish models of glutamatergic and GABAergic dysregulation in neurological and psychiatric disorders.

The zebrafish (Danio rerio) has emerged as a valuable model system in neuroscience due to their genetic tractability, conserved neuroanatomy, sensitivity to pharmacological manipulations, and suitability for high-throughput screening. Among the many applications of zebrafish in neurobiology, the investigation of glutamatergic (glutamate-based) and GABAergic (gamma-aminobutyric acid-based) signaling has gained increasing relevance, as these two neurotransmitter systems maintain the critical excitatory-inhibitory balance crucial for normal brain function. Dysregulation of this balance underlies a range of psychiatric and neurological disorders, such as epilepsy and seizure disorders, schizophrenia, anxiety-related disorders, and autism spectrum disorders. Zebrafish models demonstrate conserved receptor subtypes and behavioral phenotypes paralleling human conditions, as well as predictable responses to clinically relevant drugs, such as N-methyl-D-aspartate (NMDA) receptor antagonists, GABA agonists, and anticonvulsants. In this review, we integrate these findings to highlight how zebrafish research has contributed to understanding glutamate and GABA pathway dynamics at molecular, cellular, and behavioral levels. We critically outline experimental strategies used to model these pathologies in zebrafish and summarize key genetic, biochemical, and behavioral endpoints for assessing neurotransmitter function. Finally, we discuss current limitations and propose future directions to enhance the translational impact of zebrafish models in neuropsychiatric research.