Caffeine-Induced Neurobehavioral, Developmental Alterations and Oxidative Stress in Zebrafish: A Review Focused On Anxiety, Memory and Sleep

Caffeine, one of the most widely consumed psychoactive substances, is known to modulate central nervous system activity, but its developmental and neurotoxic effects remain insufficiently understood. The zebrafish (Danio rerio), a valuable vertebrate model for toxicological and neurobehavioral research, provides an efficient system to evaluate the impact of caffeine exposure during early development. This review investigates the dose-dependent effects of caffeine on zebrafish larvae, focusing on neurobehavioral alterations, oxidative stress markers, and developmental outcomes. Behavioral assays revealed significant changes in locomotor activity, anxiety-like responses, memory performance, and sleep patterns, suggesting alterations in neural circuitry and associated cognitive and physiological processes, suggesting altered neural circuitry. Biochemical analyses indicated increased levels of reactive oxygen species (ROS), lipid peroxidation, and modulation of antioxidant defense enzymes, highlighting oxidative stress as a potential mechanism underlying caffeine-induced toxicity. Furthermore, embryonic exposure was associated with developmental anomalies, including delayed hatching and morphological deformities at higher concentrations. Collectively, this review article highlights that caffeine exposure can disrupt neurobehavioral function, induce oxidative imbalance, and impair normal development in zebrafish, supporting its use as a model for assessing the neurotoxicological risks of psychoactive substances.