Abstract
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 (approximately 0.2 microM) DA uptake in the intact striatum.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Action Potentials / drug effects
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Action Potentials / physiology
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Animals
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Cocaine / pharmacology
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Corpus Striatum / drug effects
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Corpus Striatum / metabolism*
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Dopamine / metabolism*
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Dopamine / pharmacology
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Dopamine Plasma Membrane Transport Proteins
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Dopamine Uptake Inhibitors / pharmacology
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Electric Stimulation / instrumentation
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Electric Stimulation / methods
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Electrophysiology / instrumentation
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Electrophysiology / methods*
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Extracellular Space / drug effects
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Extracellular Space / metabolism
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Kinetics
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Male
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Membrane Glycoproteins*
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Membrane Transport Modulators
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Membrane Transport Proteins / antagonists & inhibitors
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Membrane Transport Proteins / metabolism
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Models, Neurological*
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Neostriatum / drug effects
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Neostriatum / metabolism
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Nerve Tissue Proteins*
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Nomifensine / pharmacology
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Nonlinear Dynamics
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Nucleus Accumbens / drug effects
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Nucleus Accumbens / metabolism
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Presynaptic Terminals / drug effects
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Presynaptic Terminals / metabolism*
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Rats
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Rats, Sprague-Dawley
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology*
Substances
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Dopamine Plasma Membrane Transport Proteins
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Dopamine Uptake Inhibitors
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Membrane Glycoproteins
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Membrane Transport Modulators
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Membrane Transport Proteins
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Nerve Tissue Proteins
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Nomifensine
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Cocaine
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Dopamine