Wu, Han-Chen
(2017)
DISCOVERING THE ROLE OF AUTOINHIBITION IN KINETICS HETEROGENEITY OF EVOKED DOPAMINE RESPONSES.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
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.
Share
| Citation/Export: |
|
| Social Networking: |
|
Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
22 September 2017 |
| Date Type: |
Publication |
| Defense Date: |
15 November 2016 |
| Approval Date: |
22 September 2017 |
| Submission Date: |
29 July 2017 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
54 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Chemistry |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Dopamine, electrochemistry, autoinhibition, dopamine kinetic |
| Date Deposited: |
22 Sep 2017 20:48 |
| Last Modified: |
13 Mar 2019 18:35 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/32935 |
Metrics
Monthly Views for the past 3 years
Plum Analytics
Actions (login required)
 |
View Item |
![[feed]](/images/feed-icon-32x32.png){kind=icon}