Behavioral Effects of Buspirone in Juvenile Zebrafish of Two Different Genetic Backgrounds.

Amira Abozaid,Robert Gerlai

doi:10.3390/toxics10010022

Abstract

Anxiety continues to represent a major unmet medical need. Despite the availability of numerous anxiolytic drugs, a large proportion of patients do not respond well to current pharmacotherapy, or their response diminishes with chronic drug application. To discover novel compounds and to investigate the mode of action of anxiolytic drugs, animal models have been proposed. The zebrafish is a novel animal model in this research. It is particularly appropriate, as it has evolutionarily conserved features, and drug administration can be employed in a non-invasive manner by immersing the fish into the drug solution. The first step in the analysis of anxiolytic drugs with zebrafish is to test reference compounds. Here, we investigate the effects of buspirone hydrochloride, an anxiolytic drug often employed in the human clinic. We utilize two genetically distinct populations of zebrafish, ABSK, derived from the quasi-inbred AB strain, and WT, a genetically heterogeneous wild-type population. We placed juvenile (10–13-day, post-fertilization, old) zebrafish singly in petri dishes containing one of four buspirone concentrations (0 mg/L control, 5 mg/L, 20 mg/L or 80 mg/L) for 1 h, with each fish receiving a single exposure to one concentration, a between subject experimental design. Subsequently, we recorded the behavior of the zebrafish for 30 min using video-tracking. Buspirone decreased distance moved, number of immobility episodes and thigmotaxis, and it increased immobility duration and turn angle in a quasi-linear dose dependent but genotype independent manner. Although it is unclear whether these changes represent anxiolysis in zebrafish, the results demonstrate that behavioral analysis of juvenile zebrafish may be a sensitive and simple way to quantify the effects of human anxiolytic drugs.

Highlights

Anxiety represents a large unmet medical need as despite decades of research and the development of numerous anxiolytic drugs, a large number of patients suffer from this disorder [1]
We report significant and dose-dependent behavioral changes induced by buspirone that were independent of the genotype of the juvenile zebrafish we tested
At this proof-of-concept stage we cannot ascertain whether the behavioral alterations induced by buspirone represent reduced anxiety, our results demonstrate that juvenile zebrafish may be an appropriate tool with which brain-function-altering effects of human anxiolytic drugs may be detected and screened efficiently

Summary

Introduction

Anxiety represents a large unmet medical need as despite decades of research and the development of numerous anxiolytic drugs, a large number of patients suffer from this disorder [1]. To tackle the above complex questions, well-controlled laboratory research using a variety of animal models has been proposed The majority of these studies employ traditional laboratory research organisms, i.e., the house mouse and the rat [7,8,9,10,11,12,13,14,15,16,17]. The zebrafish exhibits several evolutionarily conserved features, including high (on average about 70%) nucleotide sequence homology of its genes to that of mammalian, including human, orthologs [27,28,29] Another advantage of the zebrafish is the non-invasive and simple drug administration possible with this species. The effects of mutations and drugs can be efficiently detected by the growing number of behavioral test paradigms developed for this species [19,31,32,33,34,35]

Methods

Results

Conclusion