Shu, Zhan
(2014)
DOPAMINE IN THE RAT NUCLEUS ACCUMBENS CORE: PATCHWORK OF DOMAINS AND PREFERENTIAL EFFECTS OF NOMIFENSINE.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Dopamine (DA) is critically important in numerous aspects of normal central nervous system (CNS) function and the etiology of several CNS disorders, including Parkinson’s disease, substance abuse, and attention deficit hyperactive disorder. The diversity of DA function and dysfunction means an understanding of the mechanisms that control extracellular DA concentrations and their spatiotemporal dynamics is highly significant. Such mechanisms have been extensively studied in the subregions of the striatum, e.g. the dorsal striatum and nucleus accumbens that play central roles in motor control and reword-addiction.
To measure DA concentration changes in extracellular space, two techniques have been heavily used in the in vivo studies: microdialysis and electrochemistry. Microdialysis sampling of the brain is straightforward and has numerous applications. But implanting microdialysis probe into brain tissue causes a penetration injury. Thus, the probe samples injured tissue. In Chapter I, we used dexamethasone, a potent anti-inflammatory and immunosuppressant drug, to mitigate the effect of the penetration injury and examined its effects using fluorescence imaging and no-net- flux measurement. We conclude that dexamethasone is highly effective at suppressing gliosis and ischemia but is limited in its neuroprotective activity.
In vivo electrochemistry, using carbon fiber microelectrodes with single-digit micrometer diameter and 100-400 micrometer in detecting length coupled with fast-scan cyclic voltammetry, offers high spatial and temporal resolution with minimal tissue damage. Taking these advantages, our group has demonstrated that DA in the rat dorsal striatum is organized as a patchwork of domains that show distinct DA kinetics. In Chapter II, we demonstrated that a patchwork of domains exists in the rat nucleus accumbens core (NAcc), but shows substantial differences between the NAcc domains and those of the dorsal striatum. There are no signs of short-term plasticity during multiple consecutive stimuli nor a domain-dependent autoinhibitory tone in NAcc. In Chapter III, we examine the domain-dependent actions of nomifensine, a competitive DA transport inhibitor, in NAcc and demonstrated that it preferentially enhance evoked DA overflow in slow domains compared with fast domains. We quantified the apparent KM of DA clearance and concluded that nomifensine preferentially increases the apparent KM in NAcc compared with dorsal striatum.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
25 September 2014 |
| Date Type: |
Publication |
| Defense Date: |
13 August 2014 |
| Approval Date: |
25 September 2014 |
| Submission Date: |
14 August 2014 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
122 |
| 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, nucleus accumbens, nomifensine, voltammetry, evoked release, preferential action |
| Date Deposited: |
25 Sep 2014 14:07 |
| Last Modified: |
15 Nov 2016 14:23 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/22735 |
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