d-Fenfluramine Increases Striatal Extracellular Dopamine In Vivo Independently of Serotonergic Terminals or Dopamine Uptake Sites |
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Authors: | Philippe De Deurwaerdè re,Norbert Bonhomme,Michel Le Moal, Umberto Spampinato |
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Affiliation: | Universitéde Bordeaux II, INSERM U. 259, Bordeaux, France |
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Abstract: | Abstract: The effect of various doses of the serotonin (5-HT) release-inducing agent d -fenfluramine ( d -fenf) on extracellular dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) was studied in vivo in the striatum of halothane-anesthetized rats, following systemic and local administration. At 5 and 10 but not 2.5 mg/kg, d -fenf administered intraperitoneally significantly increased DA extracellular concentration and reduced DOPAC outflow. A concentration-dependent enhancement of DA dialysate content was also found following intrastriatal application (5, 10, 25, and 50 µ M ). The bilateral administration of 5,7-dihydroxytryptamine into the dorsal raphe nucleus, which markedly depleted 5-HT in the striatum, did not modify the effect on extracellular DA concentration of 25 µ M d -fenf locally applied into the striatum. The enhancement of extracellular DA level induced by 25 µ M d -fenf was slightly but significantly reduced by the local application of 25 µ M citalopgram. The blockade of DA uptake sites by nomifensine (0.1, 0.3, and 1 µ M ) did not modify significantly the effect of d -fenf. The rise of DA outflow induced by 25 µ M d -fenf was strongly reduced in the presence of 1 µ M tetrodotoxin (TTX) or by the removal of Ca2+ from the perfusion medium. The results obtained show that d -fenf increases the striatal extracellular DA concentration by a Ca2+-dependent and TTX-sensitive mechanism that is independent of striatal 5-HT itself or DA uptake sites. |
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Keywords: | Microdialysis Dopamine outflow d-Fenfluramine Serotonin uptake inhibitor Dopamine uptake inhibitor Striatum Halothane-anesthetized rat |
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