Opposite control of mesocortical and mesoaccumbal dopamine pathways by serotonin2B receptor blockade: Involvement of medial prefrontal cortex serotonin1A receptors
| Autor: | Renaud Rovera, Filippo Drago, Nasser Haddjeri, Pier Vincenzo Piazza, Umberto Spampinato, Francesc Artigas, Adeline Cathala, Céline Devroye |
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| Přispěvatelé: | 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 |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Microdialysis RS-127445 Nucleus accumbens 5-HT2B receptor Inhibitory postsynaptic potential 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Dorsal raphe nucleus Dopamine Dopamine release medicine 5-HT1A receptor Prefrontal cortex Pharmacology Mesocorticolimbic dopamine system 5-HT firing 030104 developmental biology medicine.anatomical_structure chemistry nervous system Neuron Psychology Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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