EXTRACELLULAR DOPAMINE AND CATABOLITES IN RAT STRIATUM DURING LACTIC-ACID PERFUSION AS DETERMINED BY IN-VIVO MICRODIALYSIS

Many experimental studies concerning hypoxia or ischemia have reported a decrease in intra/extracellular pH and massive dopamine (DA) releas e in the striatum. The present work investigated whether the increase in striatal extracellular DA is related to acidification or to lactate production. Striatal perfusion of lactic acid (pH 5.5) by microdialys is in conscious freely-moving rats induced an increase in extracellula r concentrations of DA and catabolites, homovanillic acid (HVA) and 3, 4-dihydroxyphenylacetic acid (DOPAC), as a probable result of acidific ation. Perfusion with sodium lactate (pH 7.4) failed to modify DA and catabolite release, whereas orthophosphoric acid produced the same eff ect as lactic acid. As lactic acidosis is known to induce a displaceme nt of iron from its uptake sites, the possible role of this metal in r esponse to acidosis was studied by perfusing ferrozine, an iron comple xing agent, at the same time as lactic acid. The results showed that f errous ions are involved in the process and suggested that oxygen free radicals play a role in the extracellular release of DA. Thus, lactic acid perfusion in rat striatum would appear to be a useful model for in vivo studies of the mechanisms responsible for increases in extrace llular DA during hypoxia and ischemia. (C) 1998 Published by Elsevier Science B.V. All rights reserved.