Zebrafish, a Potential Novel Research Tool for the Analysis and Modeling of Anxiety

Abstract

Although numerous medications have been developed for anxiety disorders and related neuropsychiatric conditions including phobias, these diseases still represent a large unmet medical need. This may be because despite the concerted research and drug development efforts by pharmaceutical research companies and academic laboratories alike, the mechanisms of these disorders still remain to be fully elucidated. Animal models have been proposed to accelerate research in this area. The current chapter focuses on a somewhat novel and underutilized laboratory organism, the zebrafish, which may have great utility in anxiety research. Zebrafish have been successfully utilized in developmental biology, a discipline that often employs molecular biology and genetic methods. As a result of the past three decades of intensive investigation with zebrafish, this species has become one of the favourite model organisms of geneticists. The accumulated genetic knowledge about, and the genetic methods specifically developed for the zebrafish now make this species particularly attractive for several research fields other than developmental biology. One of these fields is behavioural neuroscience. Indeed, the number of zebrafish publications in the latter field has started to exponentially increase. This may be because zebrafish strikes an optimal compromise between system complexity and practical simplicity. On the one hand it is a complex organism with brain anatomy, neurophysiology, and molecular characteristics (e.g. nucleotide sequence of its genes) highly similar to those of other vertebrates including mammals. On the other hand, it is small, easy and cheap to maintain in the laboratory and has been highly amenable to high-throughput screening (e.g. forward genetic or drug screens). The latter is particularly noteworthy for the purposes of unravelling of the genetic (and in general the biological) mechanisms of complex brain functions and the disorders of these functions. High-throughput screens may have the ability to identify a good proportion of the potentially large number of molecular players involved in these functions. The chapter discusses how the zebrafish may be utilized in the modeling of human anxiety disorders and in the analysis of the mechanisms of these disorders. Admittedly, the zebrafish is rather novel in this research and does not have a proven track record. The chapter is focussed on behavioural test paradigms that may have the capacity to induce anxiety related behavioural responses. The chapter argues that the foundation of research into the mechanisms of anxiety disorders is such behavioural paradigms as they will allow the quantification of functional changes in the brain induced by mutations or drugs and