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.
Nakazato
T
T
Department of Physiology, Juntendo University School of Medicine, Tokyo, Japan. nakazato@med.juntendo.ac.jp
Horikawa
H P
HP
Akiyama
A
A
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D017097:Electric Impedance; D004567:Electrodes, Implanted; D010134:Fenclonine / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000032:analysis*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D013469:Sulpiride / Q000494:pharmacology*; D013997:Time Factors
D018492:Dopamine Antagonists; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D013469:Sulpiride; D010134:Fenclonine