Regionally and functionally distinct serotonin3 receptors control in vivo dopamine outflow in the rat nucleus accumbens

Philippe De Deurwaerdere, Delphine Moison, Sylvia Navailles, Gregory Porras, Umberto Spampinato
J Neurochem. 2005-07-01; 94(1): 140-149
DOI: 10.1111/j.1471-4159.2005.03174.x

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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.


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