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

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.