Origin of extracellular dopamine increase induced by lactic acid striatal perfusion monitored by microdialysis in the awake rat

IN previous studies we showed that a striatal lactic acid perfusion-induced lactacidosis produces a diphasic increase in extracellular dopamine (DA). In the present study, different pharmacological reagents were used to deter mine the origin of accumulated DA. Our data show that both DA accumulations were totally suppressed by tetrodotoxin and nicardipine, indicating a rela tionship with membrane depolarization and a Ca2+-dependent effect. The firs t A peak was largely reduced by a specific inhibitor of DA uptake such as G BR-12935, and the second was totally suppressed by tyramine and reserpine a nd lowered and delayed by GBR-12935. These results compared to data in the literature suggest that the first increase in extracellular DA resulted mai nly from a release of cytosolic DA by reversal of the DA transporter, while the second was mainly due to a release of vesicular DA by exocytosis. Thes e data indicate that lactic acid perfusion helps clarify the mechanisms inv olved in this process and could be useful for the study of new treatments a gainst the hyperactive dopaminergic reaction occuring during ischemia.