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A FRAMEWORK FOR CHARACTERIZING REGIONAL ALTERATIONS IN DOPAMINE NEUROTRANSMISSION IN THE CONTEXT OF DRUGS AND DISEASE USING FAST-SCAN CYCLIC VOLTAMMETRY

Harun, Rashed (2015) A FRAMEWORK FOR CHARACTERIZING REGIONAL ALTERATIONS IN DOPAMINE NEUROTRANSMISSION IN THE CONTEXT OF DRUGS AND DISEASE USING FAST-SCAN CYCLIC VOLTAMMETRY. Doctoral Dissertation, University of Pittsburgh.

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Abstract

Dopamine (DA) has become a sort of buzzword as the ‘pleasure’ neurotransmitter that signals for natural rewards, but is ‘hijacked’ by drugs of abuse and the instant gratification we derive from our phones, Facebook, and fast-food diets in the fast-paced world we live in. In reality, DA has much more nuanced and varied functions that include the regulation of attention, working memory, motivation, movement, and even endocrine functions, which largely depends upon the region DA is acting in the brain. Dysfunction of DA neurotransmission is implicated in conditions like Parkinson’s disease (PD), attention deficit/hyperactivity disorder (ADHD), drug addiction, and traumatic brain injury (TBI) to name just a few. As such, the DAergic system represents a rational pharmaceutical target that act as DA receptor agonists, antagonists, indirect agonists, and DA reuptake inhibitors. Understanding how region-specific DA neurotransmission is altered in pathological states and following both acute and chronic drug administration, requires multi-faceted research approaches but can be significantly driven by advancements in research methodologies. It is for this reason that we hope readers will find the work contained herein particularly timely and important. Although the work contained here represents research conducted using fast-scan cyclic voltammetry (FSCV), an electrochemical method to monitor in vivo electrically stimulated DA neurotransmission that has been around since the mid 1980s, we describe the development of a novel quantitative interpretive framework for FSCV data that enhances the ability to characterize the region-specific DA neurotransmission in the context of drugs and diseases. To illustrate the utility of our framework, we demonstrate how our approach has been used to resolve the mechanistic actions of the most commonly used Parkinsonian drug, L-DOPA, on regiospecific DA neurotransmission. Moreover, our framework was utilized to characterize the regiospecific DAergic dysfunction following an experimental model of TBI and the robust neurorestorative effects of chronic methylphenidate treatment in this model. To this end, we not only describe a theoretical framework for characterizing regiospecific alterations in DA neurotransmission, but we also offer practical examples that may serve as a roadmap for studying DA neurotransmission kinetics in the context of drugs and other diseases.


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Details

Item Type: University of Pittsburgh ETD
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Harun, Rashedrah28@pitt.eduRAH28
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairTorres, Gonzalo Egtorres@pitt.eduGTORRES
Thesis AdvisorWagner, Amy Kwagnerak@upmc.eduAKW4
Committee MemberGrace, Anthony AGraceAA@pitt.eduGRACEAA
Committee MemberDixon, C Edwarddixoec@upmc.edu
Committee MemberBradberry, Charles Wbradberrycw@upmc.edu
Committee MemberGarris, Paul Apagarri@ilstu.edu
Date: 11 December 2015
Date Type: Publication
Defense Date: 27 August 2015
Approval Date: 11 December 2015
Submission Date: 11 December 2015
Release Date: 11 December 2015
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 171
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Neurobiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Fast-scan cyclic voltammetry, Dopamine, Traumatic brain injury, Neurodegeneration, Parkinson's disease, Synaptic transmission
Date Deposited: 11 Dec 2015 19:28
Last Modified: 19 Dec 2016 14:43
URI: http://d-scholarship.pitt.edu/id/eprint/26655

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