The dopamine D2 receptor antagonist sulpiride causes long-lasting serotonin release.

The effects of the dopamine D2 receptor antagonist sulpiride on extracellular levels of serotonin (5-hydroxytryptamine, 5-HT) and the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) were examined by using in vivo voltammetry. Sulpiride (1 or 3 mM, 2 microl over 24 min) was administered to freely moving rats via a cannula implanted in the striatum and 5-hydroxyindole levels were measured by using a carbon fiber voltammetry electrode implanted in the ipsilateral striatum. Six to 8 h after injection, 5-hydroxyindole levels increased 3-fold, peaked 1 to 2 days post-injection, and returned to normal levels within 2 to 4 days. These effects were suppressed by pretreatment with p-chlorophenylalanine. Two days after sulpiride injection, high-performance liquid chromatography of striatal homogenates revealed that although the 5-HT concentration was unchanged, the 5-HIAA concentration was increased significantly. These results suggest that the long-lasting elevation of 5-hydroxyindole concentrations was primarily due to increased 5-HT release.