Clozapine and haloperidol differentially alter the constitutive activity of central serotonin2C receptors in vivo.

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Navailles S, De Deurwaerdere P, Spampinato U

Clozapine and haloperidol differentially alter the constitutive activity of central serotonin2C receptors in vivo.

Biol Psychiatry. 2006 Mar 15;59(6):568-75. Epub 2005 Sep 22.

PubMed ID

16182256 [ View in PubMed

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Abstract

BACKGROUND: Central serotonin2C (5-HT2C) receptors are known to play a role in the mechanism of action of the antipsychotic drugs (APDs) clozapine and haloperidol. However, evidence for the involvement of the constitutive activity of 5-HT2C receptors in the dopamine (DA)ergic effects of APDs is lacking in vivo. METHODS: Using in vivo microdialysis in halothane-anesthetized rats, we assessed the ability of selective 5-HT2C compounds to modulate the release of DA induced by haloperidol and clozapine in the nucleus accumbens and striatum. RESULTS: Both APDs induced a dose-dependent increase in accumbal and striatal DA extracellular levels. The effect of .01 mg/kg haloperidol was potentiated by the 5-HT2C inverse agonist SB 206553 (5 mg/kg) but unaltered by the 5-HT2C antagonists SB 243213 and SB 242084 (1 mg/kg). Conversely, the effect of 1 mg/kg clozapine, a dose able to reverse the decrease in DA outflow induced by the 5-HT2C agonist Ro 60-0175 (3 mg/kg), was unaffected by SB 206553 but blocked by SB 243213 (1 mg/kg) and SB 242084 (.3 and 1 mg/kg). CONCLUSIONS: These results show that clozapine and haloperidol differentially alter the constitutive activity of 5-HT2C receptors and suggest that clozapine behaves as a 5-HT2C inverse agonist in vivo.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Clozapine	5-hydroxytryptamine receptor 2C	Protein	Humans	Unknown	Antagonist	Details