The use of the zebrafish model in stress research

Abstract

The study of the causes and mechanisms underlying psychiatric disorders requires the use of non-human models for the test of scientific hypotheses as well as for use in pre-clinical drug screening and discovery. This review argues in favor of the use of zebrafish as a novel animal model to study the impact of early (stressful) experiences on the development of differential stress phenotypes in later life. This phenomenon is evolutionary conserved among several vertebrate species and has relevance to the etiology of psychiatric disorders. Why do we need novel animal models? Although significant progress has been achieved with the use of traditional mammalian models, there are major pitfalls associated with their use that impedes progress on two major fronts: 1) uncovering of the molecular mechanisms underlying aspects of compromised (stress-exposed) brain development relevant to the etiology of psychiatric disorders, and 2) ability to develop high-throughput technology for drug discovery in the field of psychiatry. The zebrafish model helps resolve these issues. Here we present a conceptual framework for the use of zebrafish in stress research and psychiatry by addressing three specific domains of application: 1) stress research, 2) human disease mechanisms, and 3) drug discovery. We also present novel methodologies associated with the development of the zebrafish stress model and discuss how such methodologies can contribute to remove the main bottleneck in the field of drug discovery.