Neurochemical methods for the sub-second measurement of neurotransmitter release

Abstract

This dissertation is a compilation of work on the development of new methods and models to study neurochemical changes. Using fast-scan cyclic voltammetry to measure electroactive species is the common theme that ties these projects together. This electrochemical technique is the method that we have chosen to either apply to a new animal model for sub-second neurotransmitter release, zebrafish, or in conjunction with photochemistry. In the 1st chapter we discuss work that we have done to develop caged compounds for use in neurochemical experiments. We discuss work on the synthesis of caged thiols and phenols and how we have probed their photochemical mechanisms. We also discuss work we have done on developing a novel probe to measure electrochemical changes while simultaneously carrying out photochemical reactions. In the next two chapters we discuss work we have done in zebrafish studying sub-second dopamine release. We have shown that it is possible to measure dopamine release from both whole brain preparations ex vivo as well as sagittal and coronal slices. We discuss the pharmacology of this release as well as unique characteristics of the uptake plots. We also examine how different uptake inhibitors effect the kinetics of the dopamine uptake. Finally we discuss work we have done on the chemotherapy induced changes in zebrafish dopamine release. We look at 2 drugs, 5-FU and carboplatin, and two treatment pathways, habitat water and food. We show that there is a pathway dependent attenuation for both of the drugs studied that is not correlated with apparent changes in uptake. The food delivery pathway was found to have an effect on dopamine release on a much shorter time scale then the habitat water treatment pathway.