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+ (KATP) channel openers in dopamine release regulated by dopamine autoreceptors in the rat striatum. Local infusion of two KATP 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 D2 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 KATP 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 KATP channel. These data indicate that KATP channels may be present in nigrostriatal dopaminergic terminals and that striatal dopamine autoreceptors inhibit dopamine release tonically by activation of KATP channels.