WANG, YUEXIANG
(2012)
EXPLORING EXTRACELLULAR DOPAMINE CONCENTRATION AND ITS
REGULATION ON DOPAMINE RELEASE BY VOLTAMMETRY.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Extracellular dopamine (DA) is critical in regulating DA release as well as interacting with other
neurotransmission systems. Microdialysis and voltammetry are the major techniques for extracellular DA
measurement in vivo. These two techniques provide distinct results due to their different detection
volumes. Carbon fiber microelectrode is 10,000 times smaller than that of a microdialysis probe. With
such a small size, carbon fiber microelectrode provides a high spatial resolution and causes unobservable
damage to the brain which paints a completely different picture of DA release in the brain as compared to
the knowledge obtained by microdialysis.
In Chapter I, with the high temporal and spatial resolution provided by carbon fiber
microelectrode in conjunction with fast scan cyclic voltammetry (FSCV), we are able to detect DA
terminal populations with different autoinhibition levels in rat striatum. We revealed a coupling between
resting DA and local autoinhibition level. The recording sites with high resting DA concentration (micromolar)
exhibit a high autoinhibition on evoked DA release induced by medial forebrain bundle (MFB)
stimulation, and vice versa. These different types of DA release will never be observed by microdialysis
due to its large dimension. On the contrary, microdialysis result is an average of all the DA release sites
(high and low) that the microdialysis probe goes through. This averaging method could contribute to the
low measurement of the DA concentration by microdialysis.
In Chapter II, we examined the resting DA by a carbon fiber microelectrode at ~200 micron away
from a microdialysis probe. We found TTX-insensitive DA was decreased by microdialysis probe
implantation. This reduction contributes to the low DA measurement by microdialysis.
In Chapter III, we monitored evoked DA induced by MFB stimulation in the tissue near
microdialysis probe. We found DA terminals near a microdialysis probe are hyper-sensitive to D2
receptor antagonist and DA transporter inhibitor. This suggests that the DA terminals in the tissue near
microdialysis probe are under an altered neurochemical state with a loss of DA homeostasis.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
5 July 2012 |
| Date Type: |
Publication |
| Defense Date: |
12 January 2012 |
| Approval Date: |
5 July 2012 |
| Submission Date: |
2 February 2012 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
86 |
| 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: |
dopamine, voltammetry, microdialysis, autoinhibition, medial forebrain bundle, kynurenate, heterogeneity |
| Date Deposited: |
05 Jul 2012 18:33 |
| Last Modified: |
15 Nov 2016 13:55 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/10955 |
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