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Changes in the Kinetics of Dopamine Release and Uptake Have Differential Effects on the Spatial Distribution of Extracellular Dopamine Concentration in Rat Striatum
Author(s) -
Peters Jennifer L.,
Michael Adrian C.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0741563.x
Subject(s) - dopamine , striatum , nomifensine , chemistry , medicine , extracellular , biophysics , stimulation , catecholamine , endocrinology , microdialysis , biology , dopaminergic , biochemistry
The objective of this study was to examine whether thelimited diffusion distance of dopamine in rat striatum produces spatialheterogeneity in the extracellular dopamine concentration on a dimensionalscale of a few micrometers. Such heterogeneity would be significant because itwould imply that the concentration of dopamine at a given receptor depends onthe receptor's ultrastructural location. Spatially resolved measurements ofextracellular dopamine were performed in the striatum of chloralhydrate‐anesthetized rats with carbon fiber microdisk electrodes. Dopamine wasmonitored during electrical stimulation of the nigrostriatal pathway beforeand after administration of drugs that selectively affect the kinetics ofevoked dopamine release and dopamine uptake. The effects of nomifensine (20mg/kg), L‐DOPA (250 mg/kg), and α‐methyl‐ p ‐tyrosine (250 mg/kg) on the amplitude of the stimulation responses were examined. The outcome of these experiments was compared with predictions derived from a mathematical model that combines diffusion with the kinetics of release and uptake. The results demonstrate that the extracellular dopamine concentration is spatially heterogeneous on a micrometer scale and that changing the kinetics of dopamine release and uptake has different effects on this spatial distribution. The impact of these results on brain neurochemistry is considered.