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Open Access item Clozapine and olanzapine, but not haloperidol, suppress serotonin efflux in the medial prefrontal cortex elicited by phencyclidine and ketamine

Authors:Amargós-Bosch, Mercè
López-Gil, Xavier
Artigas, Francesc
Adell, Albert
Keywords:Clozapine, haloperidol, ketamine, phencyclidine, serotonin
Issue Date:Oct-2006
Publisher:Cambridge University Press
Citation:International Journal of Neuro-Psychopharmacology 9 (5) : 565-573 (2006)
Abstract:N-methyl-D-aspartate (NMDA) receptor antagonists such as phencyclidine (PCP) and ketamine can evoke psychotic symptoms in normal individuals and schizophrenic patients. Here, we have examined the effects of PCP (5 mg/kg) and ketamine (25 mg/kg) on the efflux of serotonin (5-HT) in the medial prefrontal cortex (mPFC) and their possible blockade by the antipsychotics, clozapine, olanzapine and haloperidol, as well as ritanserin (5-HT2A/2C receptor antagonist) and prazosin (alpha1-adrenoceptor antagonist). The systemic administration, but not the local perfusion, of the two NMDA receptor antagonists markedly increased the efflux of 5-HT in the mPFC. The atypical antipsychotics clozapine (1 mg/kg) and olanzapine (1 mg/kg), and prazosin (0.3 mg/kg), but not the classical antipsychotic haloperidol (1 mg/kg), reversed the PCP- and ketamine-induced increase in 5-HT efflux. Ritanserin (5 mg/kg) was able to reverse only the effect of PCP. These findings indicate that an increased serotonergic transmission in the mPFC is a functional consequence of NMDA receptor hypofunction and this effect is blocked by atypical antipsychotic drugs.
Publisher version (URL):http://journals.cambridge.org/download.php?file=/PNP/PNP9_05/S1461145705005900a.pdf&code=9fa66f23418f833fe5fb4dfe7e2a40f0
E-ISSNmetadata.dc.identifier.doi = DOI:1469-5111
Appears in Collections:(IIBB) Artículos

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