2024-03-29T00:09:08Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1596652018-06-30T04:30:47Zcom_10261_105com_10261_1col_10261_358
Opposite control of mesocortical and mesoaccumbal dopamine pathways by serotonin2B receptor blockade: Involvement of medial prefrontal cortex serotonin1A receptors
Devroyea, Céline
Haddjeri, Nasser
Cathala, Adeline
Rovera, Renaud
Drago, Filippo
Piazza, Pier Vincenzo
Artigas, Francesc
Spampinato, Umberto
Institut National de la Santé et de la Recherche Médicale (France)
Université de Bordeaux
Instituto de Salud Carlos III
Ministerio de Economía y Competitividad (España)
European Commission
Università degli Studi di Catania
5-HT2B receptor
5-HT1A receptor
Dopamine release
5-HT firing
Mesocorticolimbic dopamine system
Dorsal raphe nucleus
Recent studies have shown that serotonin2B receptor (5-HT2BR) antagonists exert opposite facilitatory and inhibitory effects on dopamine (DA) release in the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAc), respectively, thereby leading to the proposal that these compounds could provide an interesting pharmacological tool for treating schizophrenia. Although the mechanisms underlying these effects remain unknown, several data in the literature suggest that 5-HT1ARs located into the mPFC could participate in this interaction. The present study, using in vivo microdialysis and electrophysiological recordings in rats, assessed this hypothesis by means of two selective 5-HT1AR (WAY 100635) and 5-HT2BR (RS 127445) antagonists. WAY 100635, administered either subcutaneously (0.16 mg/kg, s.c) or locally into the mPFC (0.1 μM), blocked the changes of mPFC and NAc DA release induced by the intraperitoneal administration of RS 127445 (0.16 mg/kg, i.p.). The administration of RS 127445 (0.16 mg/kg, i.p.) increased both dorsal raphe nucleus (DRN) 5-HT neuron firing rate and 5-HT outflow in the mPFC. Likewise, mPFC 5-HT outflow was increased following the intra-DRN injection of RS 127445 (0.032 μg/0.2 μl). Finally, intra-DRN injection of RS 127445 increased and decreased DA outflow in the mPFC and the NAc, respectively, these effects being reversed by the intra-mPFC perfusion of WAY 100635. These results demonstrate the existence of a functional interplay between mPFC 5-HT1ARs and DRN 5-HT2BRs in the control of the DA mesocorticolimbic system, and highlight the clinical interest of this interaction, as both receptors represent an important pharmacological target for the treatment of schizophrenia.
This work was supported by grants from the Institut National de la Recherche et de la Santé (INSERM), Bordeaux University, the Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM and grant SAF2015-68346-P (MINECO-FEDER). C. Devroye was a fellowship recipient from the International Ph.D. program in Neuropharmacology, University of Catania Medical School, Catania, Italy, during the course of this study.
Peer reviewed
2018-01-25T12:18:18Z
2018-01-25T12:18:18Z
2017-06
artículo
http://purl.org/coar/resource_type/c_6501
Neuropharmacology 119: 91-99 (2017)
0028-3908
http://hdl.handle.net/10261/159665
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100004587
http://dx.doi.org/10.13039/501100006251
http://dx.doi.org/10.13039/501100001677
http://dx.doi.org/10.13039/501100000780
en
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info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-68346-P
Postprint
Sí
open
Elsevier