Contingent-behavior assay to study the neurogenetics of addiction shows zebrafish preference for alcohol is biphasic

Abstract

Alcohol use disorders are poorly understood, complex, multifactorial phenomena with a very large footprint within the global burden of diseases. Methods to study the development of addiction have primarily focused on contingent behaviors in rodents. Here, we report the development of an accessible, two-choice self-administration zebrafish assay (SAZA). Using this assay, we demonstrated that, while zebrafish avoid higher concentrations of alcohol, they are attracted to low concentrations. Pre-exposure to alcohol did not change this relative preference, and acute exposure to a deterrent decreased self-exposure to preferred concentration. A pigment mutant used in whole-brain imaging studies also displayed a similar relative preference profile but administrated substantially larger volumes of alcohol. The presence of a biphasic response (hormesis) in zebrafish validated a key aspect of vertebrate responses to alcohol. Our findings reveal the underappreciated usefulness of zebrafish in studying the neurogenetics of alcohol addiction and the discovery of novel alcohol deterrents.

Whole-Exome Sequencing to Identify Potential Genetic Risk in Substance Use Disorders: A Pilot Feasibility Study

“…The family member who shared the variants with the subject also had higher scores in the severity of dependence (Table 2; Figure 1). A loss-of-function animal model study initiated based on these results suggests that CCSER1 may indeed have a role in alcohol preference, highlighting the value of even this very small-sized trio based WES study [45]. A second point to note is that two subjects among the five with no known genetic relation (Subjects 4 and 5) shared variants in the TAS2R38 taste receptor gene.…”