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Improving the accuracy of chemical measurements in the brain: new insights into dopaminergic mechanisms by fast-scan cyclic voltammetry and microdialysis

Borland, Laura Mary (2006) Improving the accuracy of chemical measurements in the brain: new insights into dopaminergic mechanisms by fast-scan cyclic voltammetry and microdialysis. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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The neurotransmitter dopamine is implicated in cognitive function, emotion, and movement, as well as multiple disease states, like Parkinson's disease, schizophrenia, and drug abuse. Two commonly used techniques used for in the in vivo measurement of dopamine are microdialysis and voltammetry with carbon fiber microelectrodes. Unfortunately, these techniques yield conflicting results, complicating our understanding of the dopaminergic mechanisms at work in the brain. Microscopy studies reveal significant disruption to the tissue surrounding microdialysis probes, suggesting that alterations in functionality of the damaged tissue might contribute to the discrepancy between microdialysis and voltammetry. In this dissertation, microelectrodes were implanted near microdialysis probes to examine the effect of probe implantation on stimulated dopamine release and uptake in the tissue surrounding microdialysis probes. Voltammetric studies revealed a gradient in the activity of stimulated dopamine release and dopamine uptake near the probe. Additional pharmacological studies revealed a disrupted blood-brain barrier near the probe, suggesting another level of tissue disruption caused by microdialysis probe implantation.Glutamate is implicated alongside dopamine in a number of the same diseases, including schizophrenia and drug abuse. Although dopaminergic and glutamatergic projections into the striatum fail to form direct synaptic contact, an earlier voltammetric study found that local antagonism of ionotropic glutamate receptors caused a decrease in striatal dopamine levels, suggesting that glutamate acts locally within the striatum to regulate extracellular dopamine levels. This dissertation expanded on that study to reveal that ionotropic glutamate receptors control a non-vesicular release process that contributes to the resting level of extracellular dopamine in the brain.Microdialysis and voltammetry results show large discrepancies between levels of dopamine after uptake inhibition. Recent voltammetric studies suggest that D2 receptors participate in a homeostatic feedback mechanism that regulates extracellular dopamine levels after uptake inhibition. In this study, the mechanism of dopamine release after uptake inhibition in rats pretreated with a D2 receptor antagonist was identified. Dopamine released after systemic nomifensine administration in sulpiride-pretreated rats originates from an impulse-dependent (vesicular) pool of dopamine, suggesting that D2 receptors may modulate release by controlling vesicular stores and/or vesicular transport.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Borland, Laura Marylborland@pitt.eduLBORLAND
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairMichael, Adrian Camichael@pitt.eduAMICHAEL
Committee MemberBoutelle, Martyn
Committee MemberAmemiya, Shigeruamemiya@pitt.eduAMEMIYA
Committee MemberWeber, Stephen Gsweber@pitt.eduSWEBER
Date: 17 March 2006
Date Type: Completion
Defense Date: 8 November 2005
Approval Date: 17 March 2006
Submission Date: 3 October 2005
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: microelectrodes; uptake inhibition; voltammetry; dopamine; glutamate; microdialysis
Other ID:, etd-10032005-143533
Date Deposited: 10 Nov 2011 20:02
Last Modified: 15 Nov 2016 13:50


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