relation: http://d-scholarship-dev.library.pitt.edu/32935/
title: DISCOVERING THE ROLE OF AUTOINHIBITION IN KINETICS HETEROGENEITY OF EVOKED DOPAMINE RESPONSES
creator: Wu, Han-Chen
description: Dopamine (DA) contributes to critical functions in the central nervous system. By introducing electrical stimulation in vivo at the rat’s medial forebrain bundle, evoked DA signals can be measured at a carbon fiber electrode with fast scan cyclic voltammetry (FSCV) in rat’s dorsal striatum. Previously, evidence suggested that the heterogeneity in evoked DA responses reflects the difference in inherent kinetics, which might play an important role physiologically.   A restricted diffusion based numerical model produced great fit between simulations and observed responses for stimulation lengths no longer than 3 seconds, using 4 or sometimes 3 adjustable parameters. A study was designed to explore different supra-physiological stimuli and examine these evoked responses in the dorsal striatum after raclopride, a D2 antagonist drug, was given. The effects of raclopride were different based on the kinetic heterogeneity, and a refined DA kinetic model was used to model the responses up to stimulation lengths of 10 seconds. Based on the new model, it seems that the domains are different in autoinhibitory tone, which derives from different basal DA concentration required to activate the D2 receptors.   The parameters can be used to generate delivery and clearance curves that represent the DA being delivered to and cleared from the electrode at each time point. Often, multiple parameters sets will produce good fits to individual evoked responses. In these cases, however, the multiple parameter sets generate similar delivery and clearance curves. For this reason, we conclude that delivery and clearance curves provide an effective tool for investigating the kinetic properties of DA systems.
date: 2017-09-22
type: University of Pittsburgh ETD
type: PeerReviewed
format: application/pdf
language: en
identifier: http://d-scholarship-dev.library.pitt.edu/32935/1/Thesis_ETD_RW_edited.pdf
identifier:   Wu, Han-Chen  (2017) DISCOVERING THE ROLE OF AUTOINHIBITION IN KINETICS HETEROGENEITY OF EVOKED DOPAMINE RESPONSES.  Master's Thesis, University of Pittsburgh.    (Unpublished)