In vivo brain microdialysis was used to investigate the role of D3 receptors relating to dopamine auto-regulated systems in the rat. A local infusion of the dopamine D3 selective agonist, 7-OH-DPAT (100 nM), into the striatum through the dialysis membrane produced a significant decrease in extracellular concentrations of dopamine. A local application of ATP-sensitive K+ (KATP) channel blocker, quinine (10 microM, 100 microM, 1 mM), produced dose-dependent increases in extracellular concentrations of dopamine. Quinine (100 microM, 1 mM) significantly blocked a 7-OH-DPAT-induced decrease in the striatal dopamine levels in the dose-dependent manner. Because of many previous reports, the autoregulated functions of dopamine release by D3 receptors in the striatum can be regarded mainly as nerve terminal autoreceptors and/or a short-loop negative feedback system. Therefore these results suggest that KATP channels may be present in nigrostriatal dopaminergic terminals and that in the striatum, presynaptic dopamine D3 autoreceptors and/or a post-synaptic D3 related short-loop negative feedback system inhibit dopamine release tonically by the activation of KATP channels.