Theory for the impact of basal turnover on dopamine clearance kinetics in the rat striatum after medial forebrain bundle stimulation and pressure ejection

• Published in: Journal of neurochemistry 2005-09, Vol.94 (5), p.1202-1211
• Main Authors: Michael, Adrian C., Borland, Laura M., J. Mitala, Joseph, Willoughby, Bridget M., Motzko, Christina M.
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Corpus Striatum - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dopamine - administration & dosage; Dopamine - metabolism; Dopamine - pharmacokinetics; dopamine uptake; Electric Stimulation; evoked release; Extracellular Space - metabolism; Fundamental and applied biological sciences. Psychology; Injections, Jet; kinetic model; Kinetics; Medial Forebrain Bundle - physiology; Medical sciences; Models, Neurological; Neurology; Neurotransmitters; pressure ejection; Rats; Rodents; striatum; Time Factors; Vertebrates: nervous system and sense organs; voltammetry
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2005.03265.x

Although microdialysis measurements suggest that extracellular dopamine concentrations in the rat striatum are in the low nanomolar range, some recent voltammetry studies suggest that the concentration may be considerably higher, perhaps in the micromolar range. The presence of such high dopamine levels in the extracellular space has to be rationalized with the rapid, linear clearance of extracellular dopamine observed after electrical stimulation of the medial forebrain bundle. Kinetic analysis of dopamine clearance after evoked release suggests that the basal extracellular dopamine concentration is below the KM of dopamine uptake, which is near 0.2 µm. However, dopamine clearance after pressure ejection of dopamine into the rat striatum is slow and non‐linear, which may alternatively be a sign that basal dopamine release is only slightly slower than the maximal velocity of dopamine uptake, Vmax. A high basal extracellular dopamine concentration would exist if basal dopamine release were only slightly slower than the Vmax of uptake. This report introduces a new kinetic analysis of dopamine uptake that sheds light on the possible source of the different clearance rates observed following evoked dopamine release and dopamine pressure ejection. Furthermore, the analysis rationalizes the rapid dopamine clearance after evoked release with the possibility that basal extracellular dopamine levels are above the KM of the transporter.