Changes in the kinetics of dopamine release and uptake have differential effects on the spatial distribution of extracellular dopamine concentration in rat striatum

The objective of this study was to examine whether the limited diffusion di stance of dopamine in rat striatum produces spatial heterogeneity in the ex tracellular dopamine concentration on a dimensional scale of a few micromet ers. Such heterogeneity would be significant because it would imply that th e concentration of dopamine at a given receptor depends on the receptor's u ltrastructural location. Spatially resolved measurements of extracellular d opamine were performed in the striatum of chloral hydrate-anesthetized rats with carbon fiber microdisk electrodes. Dopamine was monitored during elec trical stimulation of the nigrostriatal pathway before and after administra tion of drugs that selectively affect the kinetics of evoked dopamine relea se and dopamine uptake. The effects of nomifensine (20 mg/kg), L-DOPA (250 mg/kg), and alpha-methyl-p-tyrosine (250 mg/kg) on the amplitude of the sti mulation responses were examined. The outcome of these experiments was comp ared with predictions derived from a mathematical model that combines diffu sion with the kinetics of release and uptake. The results demonstrate that the extracellular dopamine concentration is spatially heterogeneous on a mi crometer scale and that changing the kinetics of dopamine release and uptak e has different effects on this spatial distribution. The impact of these r esults on brain neurochemistry is considered.