Contingent stimulus delivery assay for zebrafish reveals a role for CCSER1 in alcohol preference

Alcohol use disorders are complex, multifactorial phenomena with a large footprint within the global burden of diseases. Here, we report the development of an accessible, two-choice self-administration zebrafish assay (SAZA) to study the neurobiology of addiction. Using this assay, we first demonstrated that, although zebrafish avoid higher concentrations of alcohol, they are attracted to low concentrations. Pre-exposure to alcohol did not change this relative preference, but acute exposure to an alcohol deterrent approved for human use decreased alcohol self-administration. A pigment mutant used in whole-brain imaging studies displayed a similar relative alcohol preference profile; however, mutants in CCSER1, a gene associated with alcohol dependence in human genetic studies, showed a reversal in relative preference. The presence of a biphasic response (hormesis) in zebrafish validated a key aspect of vertebrate responses to alcohol. SAZA adds a new dimension for discovering novel alcohol deterrents and studying the neurogenetics of addiction using the zebrafish.

Automated summary

Alcohol use disorders have significant global impact, and the development of a self-administration zebrafish assay provides a new approach to studying the neurobiology of addiction. The study demonstrates that zebrafish are attracted to low concentrations of alcohol, and acute exposure to an alcohol deterrent reduces self-administration. Mutations in the CCSER1 gene associated with alcohol dependence in humans alter the relative preference for alcohol in zebrafish. The biphasic response to alcohol in zebrafish validates the relevance of this model to vertebrate responses to alcohol.