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Clozapine decreases serotonin extracellular levels in the nucleus accumbens by a dopamine receptor independent mechanism

AuthorsFerré, Sergi; Artigas, Francesc CSIC ORCID
Nucleus accumbens
Issue Date24-Feb-1995
CitationNeuroscience Letters 187 (1) : 61-64 (1995)
AbstractBy using brain microdialysis, clear differences in the effects of the systemic administration of clozapine and haloperidol on the extracellular concentration of dopamine (DA) and serotonin (5-HT) were found in the nucleus accumbens of freely moving rats. Haloperidol (0.5 mg/kg s.c.) significantly increased DA (ca. 40%) but did not modify 5-HT extracellular concentration, while clozapine (5 mg/kg s.c.) significantly decreased 5-HT (ca. 40%) but did not change DA concentration. Locally infused, clozapine (10(-5) M) significantly increased DA (75%) and reduced 5-HT extracellular concentration (50%). The reduction of 5-HT cannot be explained by a clozapine-induced blockade of DA receptors, because the local infusion (10(-5) M) of the DA D2-like antagonist raclopride and the DA D1-like antagonist SCH 23390 significantly increased DA (ca. 300% and 200%, respectively) but did not modify 5-HT extracellular concentration. Conversely, the DA D2-like agonist quinpirole and the DA D1-like agonist SKF-38393 significantly decreased (ca. 60% in both cases) DA extracellular concentration without affecting that of 5-HT. The present results indicate that clozapine displays a powerful anti-serotoninergic effect by inhibiting 5-HT release in the nucleus accumbens, an effect probably derived from the reduction of firing activity at the dorsal raphe and by local mechanisms that may involve some 5-HT receptor subtype(s).
Publisher version (URL)http://dx.doi.org/10.1016/0304-3940(95)11338-W
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