Pharmacological (ethanol) and mutation (sam2 KO) induced impairment of novelty preference in zebrafish quantified using a new three-chamber social choice task

Abstract

Social behavior is a fundamental aspect of our own species, a feature without which our society would not function. There are numerous human brain disorders associated with abnormal social behavior, among them are the autism spectrum disorders whose causal factors include a genetic component. Environmental factors, including drugs of abuse such as alcohol, also contribute to numerous abnormalities related to social behavior. Several such disorders have been modeled using laboratory animals. Perhaps one of the newest among them is the zebrafish. However, the paucity of standardized behavioral assays specifically developed for the zebrafish have hindered progress. Here, we present a newly developed zebrafish behavioral paradigm, the three-chamber social choice task. This task, which was adapted from a murine model, assesses sociality and social novelty preference in zebrafish in three phases: habituation, phase-I to evaluate sociality, and phase-II to quantify social novelty preference. Test fish are placed in the middle chamber, while conspecifics are introduced to the flanking chambers during phase-I and II. Both male and female zebrafish displayed sociality (preference for conspecifics) during phase-I and social novelty preference (preference for unfamiliar conspecifics) during phase-II. We found the paradigm to be able to detect both environmentally (alcohol) as well as genetically (targeted knock out of sam2) induced alterations of behavioral phenotypes. Although ethanol-treated fish displayed similar levels of sociality to those of control (not alcohol exposed) male and female zebrafish, they were found to exhibit significantly impaired social novelty preference, a finding compatible with altered motivational or perhaps mnemonic processes. Moreover, we found that knock out of sam2, previously shown to lead to emotional dysregulation, also disrupted social novelty preference, while leaving sociality relatively intact. We conclude that our novel behavioral paradigm is appropriate for the modeling and quantification of social behavior deficits in zebrafish.

Keywords: Ethanol; Memory; Social novelty; Sociality; Zebrafish; sam2 chemokine.