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Closed Access item Antipsychotic drugs reverse the AMPA receptor-stimulated release of 5-HT in the medial prefrontal cortex

Authors:Amargós-Bosch, Mercè
Adell, Albert
Artigas, Francesc
Keywords:5-HT2A receptors, α1-adrenoceptors, Antipsychotic, Glutamate, Prefrontal cortex, Schizophrenia
Issue Date:Jul-2007
Citation:Journal of Neurochemistry 102(2): 550–561 (2007)
Abstract:The prefrontal cortex (PFC) is involved in the pathophysiology of schizophrenia. PFC neuronal activity is modulated by monoaminergic receptors for which antipsychotic drugs display moderate-high affinity, such as 5-HT2A and α1-adrenoceptors. Conversely, PFC pyramidal neurons project to and modulate the activity of raphe serotonergic neurons and serotonin (5-HT) release. Under the working hypothesis that atypical antipsychotic drugs may partly exert their action in PFC, we assessed their action on the in vivo 5-HT release evoked by increasing glutamatergic transmission in rat medial PFC (mPFC). This was achieved by applying S-AMPA in mPFC (reverse dialysis) or by disinhibiting thalamic excitatory afferents to mPFC with bicuculline. The application of haloperidol, chlorpromazine, clozapine and olanzapine in mPFC by reverse dialysis (but not reboxetine or diazepam) reversed the S-AMPA-evoked local 5-HT release. Likewise, the local (in mPFC) or systemic administration of these antipsychotic drugs reversed the increased prefrontal 5-HT release produced by thalamic disinhibition. These effects were shared by the 5-HT2A receptor antagonist M100907 and the α1-adrenoceptor antagonist prazosin. However, raclopride (DA D2 antagonist) had very modest effects. These results suggest that, besides their action in limbic striatum, antipsychotic drugs may attenuate glutamatergic transmission in PFC, possibly by interacting with 5-HT2A and/or α1-adrenoceptors.
Publisher version (URL):http://dx.doi.org/10.1111/j.1471-4159.2007.04532.x
E-ISSNmetadata.dc.identifier.doi = DOI:1471-4159
Appears in Collections:(IIBB) Artículos

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