The objective of the present experiments was to study the presynaptic effect of 7-hydroxy-N,N-di-n-propyl-2-aminotetraline (7-OH-DPAT, a D(2)-like dopamine receptor agonist) on [3H]-acetylcholine ([3H]-ACh) release induced by potassium (15 mM, 25 mM and 60 mM), potassium channel-blockers (4-aminopyridine, 4-AP; tetraethylammonium, TEA and quinine) and veratridine to gain insight into the mechanisms involved in the activation of the D(2) dopamine-receptor subtype located at striatal cholinergic nerve terminals. 7-OH-DPAT (1 microM) inhibited the evoked [3H]-ACh release induced by K(+) 15 mM in a similar percentage than that obtained during basal conditions (30% and 27%, respectively). Nevertheless, in the presence of 25 mM and 60 mM of K(+) the inhibitory effect of 7-OH-DPAT was completely abolished. 4-AP (1-100 microM) and TEA (1 and 5 mM) significantly enhanced [3H]-ACh release, showing 69.32%+/-7.60% (P<0.001) and 52.27%+/-5.64% (P<0.001), respectively, at the highest concentrations tested. In these conditions, 7-OH-DPAT (1 microM) inhibited the release induced by potassium channel-blockers approximately 25-27%. Quinine (0.1-1 microM) did not alter [3H]-ACh release either in the presence or absence of 7-OH-DPAT. Veratridine 10 microM evoked [3H]-ACh release in the presence of a low-calcium medium, but in such conditions 7-OH-DPAT (1 microM) did not modify the neurotransmitter release in the absence or presence of veratridine. Present data indicate that activation of the presynaptic D(2) dopamine receptor inhibits the [3H]-ACh release by increasing K(+) conductance, as high K(+) concentrations abolished the inhibitory control of 7-OH-DPAT on [3H]-ACh release. This effect could be mediated by potassium channels different from those sensitive to 4-AP, TEA and quinine. In addition, the presynaptic D(2) dopamine-receptor activation seems to not involve changes in intracellular Ca(2+).