Endogenous dopamine release from rat striatal slices and its regulation by D-2 autoreceptors: effects of uptake inhibitors and synthesis inhibition.

The effects of various dopaminergic drugs on the spontaneous and veratrine-stimulated release of endogenous dopamine (DA) from superfused rat striatal slices have been examined using a high-sensitivity HPLC system. The DA uptake inhibitor nomifensine greatly increased both veratrine-stimulated and spontaneous DA release, whilst the effects of the more potent and selective inhibitor GBR 12921 were much smaller. The DA agonists pergolide and LY 171555 reduced both spontaneous and veratrine-stimulated DA release; conversely, the D-2 selective antagonist l-sulpiride stereospecifically increased spontaneous and veratrine-stimulated release, and blocked the effects of pergolide and LY 171555. Inhibition of DA synthesis did not directly influence the actions of either pergolide or sulpiride. These studies indicate that nomifensine may have a DA-releasing action in addition to its uptake blocking action, the regulation of endogenous DA release by D-2 autoreceptors shows properties similar to those reported previously for radiolabelled DA release, with the novel finding that spontaneous release is also regulated, the autoreceptors do not appear to selectively influence newly synthesised DA release.