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Quantitative Voltammetric Analysis in the Brain: Functional Significance of Tonic Extracellular Dopamine Levels

Willoughby, Bridget Mahon (2007) Quantitative Voltammetric Analysis in the Brain: Functional Significance of Tonic Extracellular Dopamine Levels. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Extracellular (EC) dopamine (DA) levels in several regions of the brain are implicated in the rewarding effects of psychostimulants, including cocaine. These DA levels can be referred to as either tonic (long term) or phasic (short term). Microdialysis and voltammetry are currently the most popular methods to determine EC DA levels in vivo. Recently voltammetric work has demonstrated increases in phasic DA following uptake inhibition. Microdialysis studies have monitored a longer term increase in dialysate DA following uptake inhibition, but it has yet to be confirmed whether this is a phasic or tonic increase. The voltammetric procedures in our laboratory are designed to monitor tonic DA levels. In our lab, cocaine and nomifensine only increase tonic DA levels when preceded with a D2 antagonist. In this dissertation, I will discuss my work in determining the role of tonic DA levels following uptake inhibition and the functional significance of tonic DA. Initially I investigated the effect of cocaine and nomifensine on tonic EC DA levels in both the striatum and the nucleus accumbens brain regions of anesthetized animals. Cocaine and nomifensine only increased tonic DA levels when preceded with the D2 antagonist, raclopride. Similar results were found in unanaesthetized animals, leading to the conclusion that the lack of response following uptake inhibition was not an anesthetic effect. These findings introduce the novel concept that tonic DA levels in the striatum and nucleus accumbens are stabilized following uptake inhibition, and this Additionally, voltammetric recordings were conducted in the nucleus accumbens of an unanesthetized rat that received cocaine after pretreatment with raclopride in order to evaluate cocaine-induced hyperactivity. The combination of raclopride and cocaine produced two treatment outcomes, a tonic increase in EC DA levels and locomotor activation. However, these treatment outcomes were mutually exclusive in that individual animals exhibited one outcome or the other but, with one exception, not both. This data suggests that tonic elevations of EC DA suppress cocaine-induced hyperactivity. By quantitatively measuring DA levels via voltammetry, we observe an entirely new phenomenon: an excess of DA in the EC space decreases activity.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Willoughby, Bridget Mahonbrm8@pitt.eduBRM8
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairMichael, Adrianamichael@pitt.eduAMICHAEL
Committee MemberBradberry, Charlesbradberr@pitt.eduBRADBERR
Committee MemberAmemiya, Shigeruamemiya@pitt.eduAMEMIYA
Committee MemberWeber, Stephensweber@pitt.eduSWEBER
Date: 27 September 2007
Date Type: Completion
Defense Date: 5 July 2007
Approval Date: 27 September 2007
Submission Date: 25 June 2007
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: Dopamine; voltammetry
Other ID:, etd-06252007-150351
Date Deposited: 10 Nov 2011 19:48
Last Modified: 15 Nov 2016 13:45


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