Monosodium glutamate disrupts zebrafish sleep-like state likely through activation of peripheral nervous system glutamate receptors

Monosodium glutamate (MSG), a widely used flavor enhancer, has raised concerns about its effects on behavior and sleep. This study investigates how MSG influences zebrafish sleep-like state (SLS) and interacts with other substances affecting neurobehavioral responses. Adult zebrafish were exposed to MSG at concentrations of 50, 100, and 150 mg/L, and their swimming speeds and SLS durations were recorded over a 14-hour night period. The results indicated that higher MSG concentrations increased swimming speeds and decreased SLS duration, suggesting heightened excitability and reduced sleep recovery. The study further evaluated how MSG impacts anesthesia sensitivity induced by 2-phenoxyethanol (POE) compared to alcohol and nicotine. Zebrafish were pre-treated with 50 mg/L MSG, 0.5% alcohol, or 0.5 mg/L nicotine before being anesthetized with POE. Nicotine decreased anesthesia sensitivity in a concentration-dependent manner by enhancing neurotransmitter release. In contrast, MSG and alcohol had minimal effects on anesthesia. The limited impact of MSG on anesthesia sensitivity suggests that MSG primarily affects peripheral nervous system functions rather than central nervous system functions, likely due to its poor ability to cross the blood-brain barrier. Overall, the findings demonstrate that MSG disrupts zebrafish behavior through peripheral mechanisms, affecting both swimming activity and sleep patterns. Nicotine, on the other hand, influences behavior through central nervous system interactions. These results highlight the need for further research to better understand how dietary additives like MSG impact neurobehavioral functions in aquatic models, offering insights into their broader implications for sleep and behavior.