The Role of Ethanol Pre-Exposure in Ethanol-Induced Behavioral Responses and Reward Pathways in Zebrafish (Danio rerio)

Alcohol exposure in adolescence is thought to be a contributing factor toward reward- seeking behavior in adulthood. This reward-seeking behavior may be assessed in animal models using the conditioned place preference (CPP) paradigm. In this study, ethanol-induced change in time spent on the initially non-preferred tank side in zebrafish was studied by conditioning adult zebrafish to ethanol dissolved in water (0.00% 1.00%; 1.25%; 1.50%; 1.60%; 1.75% vol/vol) paired with an initially non-preferred environment. Following a single conditioning cycle, fish were allowed to swim unrestricted in the CPP chamber to assess changes in preference. Immunohistochemical changes in dopaminergic and GABAergic circuitry within the brain were examined to determine possible mechanisms through which the experience of alcohol exposure in early life may alter preference for an alcohol-paired environment. Western Blots were also used to quantify neurochemical changes in the brain of these same individual subjects. Daily 20-minute pre-exposure to ethanol for 1 week during the juvenile stage starting at either 20 days post fertilization (dpf) or 40 dpf altered percent time spent on the ethanol-paired side in adulthood in a dose-dependent and sex-dependent manner. Ethanol pre-exposure also altered localization and levels of tyrosine hydroxylase (TH) in the zebrafish brain, suggesting that zebrafish may be utilized as an effective model in which to investigate behavioral correlates of ethanol-induced changes in neural circuits implicated in reward.