کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4181348 | 1276656 | 2006 | 8 صفحه PDF | دانلود رایگان |
BackgroundCentral 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.MethodsUsing 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.ResultsBoth 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).ConclusionsThese 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.
Journal: Biological Psychiatry - Volume 59, Issue 6, 15 March 2006, Pages 568–575