A functional response to D1 dopamine receptor stimulation in the central nervous system: inhibition of the release of [3H]-serotonin from the rat substantia nigra

Abstract

The influence of dopamine receptor agonists on the calcium dependent electrically-evoked release of [3H]-serotonin was studied in the superfused rat substantia nigra. The electrically-evoked overflow of [3H]-serotonin was significantly inhibited by micromolar concentrations of exogenous dopamine and of the D1-selective dopamine receptor agonists, fenoldopam and SKF 38393. The inhibitory effects of dopamine and fenoldopam on [3H]-serotonin release were antagonized by the D1-selective dopamine receptor antagonist SCH 23390. S-sulpiride, an antagonist of D2 receptors failed to antagonize the inhibitory effects of dopamine on [3H]-serotonin release. Moreover, quinperol, the selective D2 receptor agonist did not modify the electrically evoked release of [3H]-serotonin. In the presence of nomifensine, SCH 23390 but not S-sulpiride enhanced in a concentration dependent manner the electrically-evoked release of [3H]-serotonin. Under similar experimental conditions, exposure to fenoldopam did not inhibit the electrically-evoked release of [3H]-serotonin from rat hippocampal or hypothalamic slices. These results indicate that, in rat substantia nigra, exogenous as well as endogenous dopamine causes inhibition of serotonin release by activation of dopamine receptors of the D1-subtype.