Embryonic ethanol exposure and optogenetic activation of hypocretin neurons stimulate similar behaviors early in life associated with later alcohol consumption

The initiation of alcohol use early in life is one of the strongest predictors of developing a future alcohol use disorder. Clinical studies have identified specific behaviors during early childhood that predict an increased risk for excess alcohol consumption later in life. These behaviors, including increased hyperactivity, anxiety, novelty-seeking, exploratory behavior, impulsivity, and alcohol-seeking, are similarly stimulated in children and adolescent offspring of mothers who drink alcohol during pregnancy. Here we tested larval zebrafish in addition to young pre-weanling rats and found this repertoire of early behaviors along with the overconsumption of alcohol during adolescence to be increased by embryonic ethanol exposure. With hypocretin/orexin (Hcrt) neurons known to be stimulated by ethanol and involved in mediating these alcohol-related behaviors, we tested their function in larval zebrafish and found optogenetic activation of Hcrt neurons to stimulate these same early alcohol-related behaviors and later alcohol intake, suggesting that these neurons have an important role in producing these behaviors. Together, these results show zebrafish to be an especially useful animal model for investigating the diverse neuronal systems mediating behavioral changes at young ages that are produced by embryonic ethanol exposure and predict an increased risk for developing alcohol use disorder.