Embryonic exposure to fentanyl induces behavioral changes and neurotoxicity in zebrafish larvae

The use of fentanyl during pregnancy, whether by prescription or illicit use, may result in high blood levels that pose an early risk to fetal development. However, little is known regarding the neurotoxicity that might arise from excessive fentanyl exposure in growing organisms, particularly drug-related withdrawal symptoms. In this study, zebrafish embryos were exposed to fentanyl solutions (0.1, 1, and 5 mg/L) for 5 days post fertilization (dpf), followed by a 5-day recovery period, and then the larvae were evaluated for photomotor response, anxiety behavior, shoaling behavior, aggression, social preference, and sensitization behavior. Fentanyl solutions at 1 and 5 mg/L induced elevated anxiety, decreased social preference and aggressiveness, and behavioral sensitization in zebrafish larvae. The expression of genes revealed that embryonic exposure to fentanyl caused substantial alterations in neural activity (bdnf, c-fos) and neuronal development and plasticity (npas4a, egr1, btg2, ier2a, vgf). These results suggest that fentanyl exposure during embryonic development is neurotoxic, highlighting the importance of zebrafish as an aquatic species in research on the neurobehavioral effects of opioids in vertebrates.