D-FENFLURAMINE INCREASES STRIATAL EXTRACELLULAR DOPAMINE IN-VIVO INDEPENDENTLY OF SEROTONERGIC TERMINALS OR DOPAMINE UPTAKE SITES

The effect of various doses of the serotonin (5-HT) release-inducing a gent d-fenfluramine (d-fenf) on extracellular dopamine (DA), 3,4-dihyd roxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) was studied in vivo in the striatum of halothane-anesthetized rats, f ollowing 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 followin g intrastriatal application (5, 10, 25, and 50 mu M). The bilateral ad ministration of 5,7-dihydroxytryptamine into the dorsal raphe nucleus, which markedly depleted 5-HT in the striatum, did not modify the effe ct on extracellular DA concentration of 25 mu M d-fenf locally applied into the striatum. The enhancement of extracellular DA level induced by 25 mu M d-fenf was slightly but significantly reduced by the local application of 25 mu M citalopram. The blockade of DA uptake sites by nomifensine (0.1, 0.3, and 1 mu M) did not modify significantly the ef fect of d-fenf. The rise of DA outflow induced by 25 mu M d-fenf was s trongly reduced in the presence of 1 mu 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 str iatal 5-HT itself or DA uptake sites.