ATP-sensitive K + channel openers block sulpiride-induced dopamine release in the rat striatum

Abstract

In vivo brain microdialysis was used to investigate the role of ATP-sensitive K + (K ATP) channel openers in dopamine release regulated by dopamine autoreceptors in the rat striatum. Local infusion of two K ATP channel openers, nicorandil (10 −5–10 −3 M) and cromakalim (10 −5–10 −3 M), into the striatum thorough the dialysis membrane produced dose-dependent decreases in extracellular concentrations of dopamine. Local application of the dopamine D 2 receptor antagonist, (−)-sulpiride (10 −5 M), produced significant increases in extracellular concentrations of dopamine. Both nicrorandil (10 −5 M) and cromakalim (10 −4 M) blocked significantly (−)-sulpiride (10 −5 M)-induced increases in dopamine levels in the striatum. These results suggest that activation of K ATP channels in the striatum causes decreases in endogenous dopamine release in vivo. Furthermore, the sulpiride-induced increases in dopamine levels caused by blocking the tonic activation of dopamine autoreceptors were inhibited by activation of K ATP channel. These data indicate that K ATP channels may be present in nigrostriatal dopaminergic terminals and that striatal dopamine autoreceptors inhibit dopamine release tonically by activation of K ATP channels.