Many data suggest that the presence of dopamine (DA) is a prerequisite for the development of neuronal damage in the striatum; neural injury could be initiated by a massive release from dopaminergic nerve terminals during ischemia. The current study was undertaken in order to define the mechanism through which ischemia alters dopaminergic neurotransmission, and to examine the subsequent events early during recirculation. Experiments were performed on 14 male anesthetized Sprague Dawley rats. The ischemic insult consisted of 20 min global cerebral ischemia (4-vessel occlusion) followed by 80 min reperfusion. Cardiac arrest concluded this phase of the experiment, but measurements were continued for 60 min more. Measurements of catechols were made in the striatum using in vivo differential pulse voltammetry (DPV), each 4 min, throughout the experiment and for 60 min post-mortem. DPV data were substantiated with intracerebral dialysis; 20 min dialysate samples were analysed for dopamine (DA) and homovanillic acid (HVA; DA metabolite) using high performance liquid chromatography (HPLC). Repeated in vivo DPV measurements of striatal catechols during ischemia/reperfusion were collected in 11 of 14 experiments. In 6 out of 11 rats, ischemia induced a massive catechols release in the striatum, resulting in a marked increase in extracellular level (350 to 1200% of control), which persisted throughout ischemia. In these rats, a marked rise in extracellular DA was detected in the dialysate sample collected in the contralateral striatum during ischemia, together with a fall in HVA, probably due to ischemic inhibition of the enzymatic oxidation of DA. Catechol was cleared from the extracellular space within minutes of reperfusion, indicating functional catechol uptake.(ABSTRACT TRUNCATED AT 250 WORDS)