Multigenerational effects of alcohol: A behavioral study in three zebrafish populations

Fetal alcohol exposure can result in fetal alcohol spectrum disorder (FASD), which encompasses a range of cognitive and behavioral impairments. Although zebrafish have been used as a reliable model to study FASD, little is known about the ontogeny of this disorder and population differences in subsequent generations not directly exposed to alcohol. In this study, we evaluated the behavioral outcomes of zebrafish populations AB, Outbred (OB), and Tubingen (TU), offspring of parents exposed to alcohol during embryonic development. The offspring of adult fish with FASD (exposed to 1 % alcohol at the embryonic stage) was compared to the offspring of unexposed parental fish (0 % alcohol at the embryo phase). The behavioral profile of the offspring was assessed at 6 days post-fertilization (dpf) and 45 dpf. At 6dpf, the AB FASD offspring exhibited hyperactivity and increased time at the edge of the tank, while the TU and OB FASD offspring showed hypoactivity. At 45dpf, TU fish maintained the larval locomotor pattern, characterized by decreased average speed and total distance traveled and increased immobility. However, AB and OB fish did not show alterations in locomotor activity and anxiety-related responses at 45dpf. Our results demonstrate, for the first time, that FASD zebrafish offspring display behavioral differences, which were most evident during the early ontogenetic phase (6dpf) but may vary throughout animal ontogeny. TU fish exhibited the most consistent behavioral pattern across different developmental stages. These findings provide insights into the multigenerational and persistent behavioral consequences of embryonic alcohol exposure in zebrafish. Further research should focus on other features that can be inherited and the development of treatments for the offspring affected by it.