Many experimental studies concerning
hypoxia or
ischemia have reported a decrease in intra/extracellular pH and massive
dopamine (DA) release 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 microdialysis in conscious freely-moving rats induced an increase in extracellular concentrations of DA and catabolites,
homovanillic acid (HVA) and
3,4-dihydroxyphenylacetic acid (
DOPAC), as a probable result of acidification. Perfusion with
sodium lactate (pH 7.4) failed to modify DA and catabolite release, whereas
orthophosphoric acid produced the same effect as
lactic acid. As
lactic acidosis is known to induce a displacement of
iron from its uptake sites, the possible role of this
metal in response to
acidosis was studied by perfusing
ferrozine, an
iron complexing agent, at the same time as
lactic acid. The results showed that ferrous
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 extracellular DA during
hypoxia and
ischemia.