Dopamine Release and Uptake in Animal Models of Neurological Diseases

Abstract

Fast scan cyclic voltammetry (FSCV) can be utilized to detect neurotransmitter release and uptake in brain slices. When combining this technique with disease state animals models, information for therapeutic targets can be obtained. Herein, the evaluation of stimulated dopamine release and uptake in animal models was used in conjunction with pharmacological agents to assess neurological problems caused by Fragile X syndrome and chemotherapy. Fragile X Syndrome, a genetic form of mental retardation caused by a trinucleotide repeat expansion, was investigated by combining behavioral analysis and FSCV to determine alterations in dopamine release, dopamine uptake, effects of amphetamine treatments, and the functionality of the D2 autoreceptor. Side effects of chemotherapy can include alteration in neurological function and were investigated by using FSCV to monitor for effect on dopamine release and uptake patterns in the striatum of rats being dosed with Carboplatin, a chemotherapeutic drug. Finally, instrumentation was established to use caged compounds to photo release glutamate while collecting FSCV data of dopamine release to evaluate instantaneous effects of glutamate on the dopamine system in brain slices.