Effect of cocaine and 5-HT3 receptor antagonists on 5-HT-induced [3H]dopamine release from rat striatal synaptosomes.
The effect of serotonin (5-HT) on the release of tritium from striatal synaptosomes previously loaded with [3H]dopamine ([3H]DA) was studied. 5-HT stimulated both the spontaneous and Ca(2+)-evoked efflux of tritium in a concentration-dependent manner. This effect was not mimicked by the non-selective 5-HT agonist, d-lysergic acid diethylamide. Further, the stimulatory effects of 5 muM 5-HT were unaffected by the selective 5-HT3 receptor antagonists, MDL-72222 and GR-38032F. On the other hand, cocaine and the selective DA uptake inhibitor, nomifensine completely antagonized the effect of 5 muM 5-HT on spontaneous tritium efflux with IC50 values of 0.2 and 0.09 muM, respectively. The effect of 5-HT on Ca(2+)-evoked tritium efflux was also blocked by these DA uptake inhibitors, albeit at somewhat higher concentrations. These data support the hypothesis that 5-HT induces the release of DA from striatal nerve terminals via a mechanism involving the transport of 5-HT into the dopaminergic terminal, rather than by activating 5-HT3 receptors as has been proposed to account for the effect of 5-HT observed in striatal slices.
Yi
S J
SJ
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550.
Gifford
A N
AN
Johnson
K M
KM
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D009627:Nomifensine / Q000494:pharmacology; D017294:Ondansetron; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology*; D012702:Serotonin Antagonists; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D014326:Tropanes / Q000494:pharmacology
D007093:Imidazoles; D012702:Serotonin Antagonists; D014326:Tropanes; D009627:Nomifensine; D012701:Serotonin; D017294:Ondansetron; D008238:Lysergic Acid Diethylamide; D003042:Cocaine; C042253:bemesetron; D002118:Calcium; D004298:Dopamine