Determination of release and uptake parameters from electrically evoked dopamine dynamics measured by real-time voltammetry

Quantifying mechanisms underlying extracellular signaling by the neurotransmitter dopamine (DA) is a difficult task, particularly in the complex extracellular microenvironment of the intact brain. In this study, two methods for evaluating release and uptake from DA dynamics monitored by real-time vo...

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Bibliographic Details
Published in:Journal of neuroscience methods 2001-12, Vol.112 (2), p.119-133
Main Authors: Wu, Qun, Reith, Maarten E.A., Wightman, R.Mark, Kawagoe, Kirk T., Garris, Paul A.
Format: Article
Language:English
Subjects:
Action Potentials - drug effects
Action Potentials - physiology
Animals
Biological and medical sciences
Caudate-putamen
Cocaine - pharmacology
Corpus Striatum - drug effects
Corpus Striatum - metabolism
Dopamine
Dopamine - metabolism
Dopamine - pharmacology
Dopamine Plasma Membrane Transport Proteins
Dopamine Uptake Inhibitors - pharmacology
Electric Stimulation - instrumentation
Electric Stimulation - methods
Electrophysiology - instrumentation
Electrophysiology - methods
Extracellular Space - drug effects
Extracellular Space - metabolism
Fundamental and applied biological sciences. Psychology
General aspects. Models. Methods
Kinetics
Male
Membrane Glycoproteins
Membrane Transport Modulators
Membrane Transport Proteins - antagonists & inhibitors
Membrane Transport Proteins - metabolism
Models, Neurological
Neostriatum - drug effects
Neostriatum - metabolism
Nerve Tissue Proteins
Nomifensine - pharmacology
Nonlinear Dynamics
Nucleus accumbens
Nucleus Accumbens - drug effects
Nucleus Accumbens - metabolism
Presynaptic Terminals - drug effects
Presynaptic Terminals - metabolism
Rats
Rats, Sprague-Dawley
Release
Synaptic Transmission - drug effects
Synaptic Transmission - physiology
Uptake
Vertebrates: nervous system and sense organs
Voltammetry
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Description
Summary:Quantifying mechanisms underlying extracellular signaling by the neurotransmitter dopamine (DA) is a difficult task, particularly in the complex extracellular microenvironment of the intact brain. In this study, two methods for evaluating release and uptake from DA dynamics monitored by real-time voltammetry are described. Both are based on a neurochemical model characterizing electrically evoked levels of DA as a balance between these opposing mechanisms. The theoretical basis of what is called here nonlinear regression and single curve analyses is given. Fitting simulated data tests the reliability of the methods. The two analyses are also compared with an experimental data set describing the effects of pharmacologically inhibiting the DA transporter in the caudate-putamen (CP) and nucleus accumbens (NAc). The results indicate that nonlinear regression and single curve analyses are suitable for quantifying release and uptake mechanisms underlying DA neurotransmission. Additionally, the most important experimental finding of this technical study was the independent confirmation of high affinity (≈0.2 μM) DA uptake in the intact striatum.
ISSN:0165-0270
1872-678X
DOI:10.1016/S0165-0270(01)00459-9