Regionally and functionally distinct serotonin3 receptors control in vivo dopamine outflow in the rat nucleus accumbens.
Central serotonin(3) (5-HT(3)) receptors control the mesoaccumbens dopamine (DA) pathway. This control is thought to be conditional and might involve regionally distinct subpopulations of 5-HT(3) receptors. Here, using in vivo microdialysis in rats, we assessed the relative contribution of nucleus accumbens (Nacc) 5-HT(3) receptors to the overall influence exerted by 5-HT(3) receptors on accumbal DA release induced by different drugs or treatments. In freely moving rats, pre-treatment with 5-HT(3) antagonists (0.1 mg/kg ondansetron and/or 0.03 mg/kg MDL 72222, s.c.) reduced DA efflux enhanced by morphine (1-10 mg/kg, s.c.) and haloperidol (0.01 mg/kg, s.c.), but not amphetamine (1-2.5 mg/kg, i.p.) or cocaine (10-20 mg/kg, i.p.), the latter two drugs do not trigger depolarization-stimulated DA exocytosis. Intra-Nacc administration of ondansetron (1 microm) in freely moving rats reduced the DA effects elicited by 10 mg/kg morphine, but not 1 mg/kg morphine or haloperidol. The 5-HT(1A) agonist 8-OH-DPAT (0.1 mg/kg, s.c.), known to decrease central 5-HT tone, reduced 10 but not 1 mg/kg morphine-stimulated DA outflow in freely moving rats. In halothane-anaesthetized rats, intra-Nacc ondansetron (1 microm) application reduced dorsal raphe nucleus electrical stimulation (20Hz)-induced DA outflow. Our results show that regionally distinct populations of 5-HT(3) receptors control the depolarization-dependent exocytosis of DA and suggest that the involvement of Nacc 5-HT(3) receptors occurs only when central DA and 5-HT tones are concomitantly increased.
De Deurwaerdère
Philippe
P
Unité Mixte de Recherche-Centre National de la Recherche Scientifique 5541, Université Victor Segalen Bordeaux 2, France.
Moison
Delphine
D
Navailles
Sylvia
S
Porras
Grégory
G
Spampinato
Umberto
U
D000818:Animals; D015314:Dialysis Solutions / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044406:Receptors, Serotonin, 5-HT3 / Q000502:physiology*; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology
D015314:Dialysis Solutions; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists; D004298:Dopamine