A systematic comparison of the effects of iontophoresed dopamine (DA) was carried out in the neostriatum (NS), nucleus accumbens (Acb) and anterior cingulate (ACg), prefrontal (PF) and parietal (Par) cortex of urethane-anesthetized rats, before and after treatment with the specific DA uptake blockers GBR 12909 and Bupropion. Similar experiments were also conducted after DA denervation with 6-hydroxydopamine and after DA depletion with a-methyl-p-tyrosine. The average rate of spontaneous neuronal firing was comparable in all regions, except in the NS after DA depletion. A majority of the units were inhibited by DA in every region and condition tested. As assessed with the ITso index, the responsiveness to DA was not markedly different between regions, indicating that the postsynaptic sensitivity to this amine is independent of the density of DA receptors and of DA innervation. In contrast, the average duration of DA inhibitions (RT,,) was considerably longer (5-fold) in the intact ACg than in the PF, Par, NS, or Acb. Moreover, treatment with both DAuptake blockers reduced the duration of DAinhibitions in ACg (4-to 9-fold); while lengthening it in PF, NS and Acb; and having no apparent effect in Par. DA depletion and DA denervation also reduced the duration of the DA inhibitions in ACg without effect in Par. Taken together, these results provide further evidence for the existence of a presynaptic, positive-feedback mechanism in ACg, triggered by DA, and favouring the futher release of this transmitter upon its reuptake in DA nerve terminals.