Zebrafish (Danio rerio) as a Model Organism for Dopamine Transporter Deficiency Syndrome

Dopamine transporter deficiency syndrome (DTDS) is a pharmacoresistant transportopathy in which the patient has a loss of function mutation in the dopamine transporter. Fast scan cyclic voltammetry (FSCV) is an electrochemical technique that allows the detection of the release and reuptake of neurotransmitters. This project aims to use FSCV to characterise the electrically stimulated release and reuptake of dopamine in the zebrafish (Danio rerio) dopamine transporter mutant (dat/slc6a3) aided by comparison to the AB/AB wild-type zebrafish. This characterisation of dopaminergic signalling aims to establish zebrafish as a model organism for dopamine transporter deficiency syndrome and to provide a basis for exploration of the pathophysiological mechanism of the disease. The first results chapter focuses on optimising FSCV for dopamine detection in the zebrafish brain. The second chapter evaluates the ability of a calibration set of cyclic voltammograms to resolve the neurochemical composition of solutions via principal component regression analysis. The third chapter focuses on characterising the DTDS mutant line using FSCV. There are currently few treatments available for this disorder and more animal models are needed for research. The general discussion will aim to explore future outlooks for further exploration and treatment. There were limitations with FSCV in the zebrafish brain, which raises interesting possibilities for analytical approaches in novel models and the importance of tools that separate individual neurotransmitter contributions. This thesis is believed to be the first to use FSCV in a mutant zebrafish line.