In Vivo Evidence that 5-HT2C Receptor Antagonist but not Agonist Modulates Cocaine-Induced Dopamine Outflow in the Rat Nucleus Accumbens and Striatum
Neuropsychopharmacol. 2003-10-15; 29(2): 319-326
DOI: 10.1038/sj.npp.1300329
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During recent years, much attention has been devoted at investigating the
modulatory role of central 5-HT(2C) receptors on dopamine (DA) neuron activity,
and it has been proposed that these receptors modulate selectively DA exocytosis
associated with increased firing of DA neurons. In the present study, using in
vivo microdialysis in the nucleus accumbens (NAc) and the striatum of
halothane-anesthetized rats, we addressed this hypothesis by assessing the
ability of 5-HT(2C) agents to modulate the increase in DA outflow induced by
haloperidol and cocaine, of which the effects on DA outflow are associated or not
with an increase in DA neuron firing, respectively. The intraperitoneal
administration of cocaine (10-30 mg/kg) induced a dose-dependent increase in DA
extracellular levels in the NAc and the striatum. The effect of 15 mg/kg cocaine
was potentiated by the mixed 5-HT(2C/2B) antagonist SB 206553 (5 mg/kg i.p.) and
the selective 5-HT(2C) antagonist SB 242084 (1 mg/kg i.p.) in both brain regions.
The mixed 5-HT(2C/2B) agonist, Ro 60-0175 (1 mg/kg i.p.), failed to affect
cocaine-induced DA outflow, but reduced significantly the increase in DA outflow
induced by the subcutaneous administration of 0.1 mg/kg haloperidol. The obtained
results provide evidence that 5-HT(2C) receptors exert similar effects in both
the NAc and the striatum, and they modulate DA exocytosis also when its increase
occurs independently from an increase in DA neuron impulse activity. Furthermore,
they show that 5-HT(2C) agonists, at variance with 5-HT(2C) antagonists, exert a
preferential control on the impulse-stimulated release of DA.