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d ‐Fenfluramine Increases Striatal Extracellular Dopamine In Vivo Independently of Serotonergic Terminals or Dopamine Uptake Sites
Author(s) -
De Deurwaerdère Philippe,
Bonhomme Norbert,
Le Moal Michel,
Spampinato Umberto
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.65031100.x
Subject(s) - extracellular , dopamine , microdialysis , striatum , chemistry , serotonergic , nomifensine , homovanillic acid , medicine , endocrinology , serotonin , biology , dopaminergic , biochemistry , receptor
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 Ca 2+ from the perfusion medium. The results obtained show that d ‐fenf increases the striatal extracellular DA concentration by a Ca 2+ ‐dependent and TTX‐sensitive mechanism that is independent of striatal 5‐HT itself or DA uptake sites.