Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/164978
Title: Selective Enhancement of Mesocortical Dopaminergic Transmission by Noradrenergic Drugs: Therapeutic Opportunities in Schizophrenia
Author: Masana Nadal, Mercè
Bortolozzi Biasoni, Analía
Artigas Pérez, Francesc
Keywords: Antipsicòtics
Escorça frontal
Dopamina
Noradrenalina
Antipsychotic drugs
Prefrontal cortex
Dopamine
Noradrenaline
Issue Date: 12-Aug-2010
Publisher: Oxford University Press
Abstract: The superior efficacy of atypical vs. classical antipsychotic drugs to treat negative symptoms and cognitive deficits in schizophrenia appears related to their ability to enhance mesocortical dopamine (DA) function. Given that noradrenergic (NE) transmission contributes to cortical DA output, we assessed the ability of NE-targeting drugs to modulate DA release in medial prefrontal cortex (mPFC) and nucleus accumbens (NAc), with the aim of selectively increasing mesocortical DA. Extracellular DA was measured using brain microdialysis in rat mPFC and NAc after local/systemic drug administration, electrical stimulation and selective brain lesions. Local GBR12909 [a selective DA transporter (DAT) inhibitor] administration increased DA output more in NAc than in mPFC whereas reboxetine [a selective NE transporter (NET) inhibitor] had an opposite regional profile. DA levels increased comparably in both regions of control rats after local nomifensine (DAT+NET inhibitor) infusion, but this effect was much lower in PFC of NE-lesioned rats (DSP-4) and in NAc of 6-OHDA-lesioned rats. Electrical stimulation of the locus coeruleus preferentially enhanced DA output in mPFC. Consistently, the administration of reboxetine+RX821002 (an α2-adrenoceptor antagonist) dramatically enhanced DA output in mPFC (but not NAc). This effect also occurred when reboxetine+RX821002 were co-administered with haloperidol or clozapine. The preferential contribution of the NE system to PFC DA allows selective enhancement of DA transmission by simultaneously blocking NET and α2-adrenoceptors, thus preventing the autoreceptor-mediated negative feedback on NE activity. Our results highlight the importance of NET and α2-adrenoceptors as targets for treating negative/cognitive symptoms in schizophrenia and related psychiatric disorders.
Note: Reproducció del document publicat a: https://doi.org/10.1017/S1461145710000908
It is part of: International Journal of Neuropsychopharmacology, 2011, vol. 14, num. 1, p. 53-68
URI: http://hdl.handle.net/2445/164978
Related resource: https://doi.org/10.1017/S1461145710000908
ISSN: 1461-1457
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Biomedicina)

Files in This Item:
File Description SizeFormat 
683440.pdf1.95 MBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.