Opposite control of mesocortical and mesoaccumbal dopamine pathways by serotonin2B receptor blockade: Involvement of medial prefrontal cortex serotonin1A receptors

NEUROPHARMACOLOGY

卷:119

Article

Devroye, Celine^1,2  Haddjeri, Nasser^3,4  Cathala, Adeline^1,2  Rovera, Renaud^3,4  Drago, Filippo⁵  Piazza, Pier Vincenzo^1,2  Artigas, Francesc^6,7  Spampinato, Umberto^1,2 

[1] Inserm U1215, Neuroctr Magendie, Physiopathol Addict & Traumat Memories Grp, F-33000 Bordeaux, France

[2] Univ Bordeaux, F-33000 Bordeaux, France

[3] Inserm U1208, Stem Cell & Brain Res Inst, F-69500 Bron, France

[4] Univ Lyon 1, F-69373 Lyon, France

[5] Univ Catania, Sect Pharmacol, Dept Biomed & Biotechnol Sci, I-95125 Catania, Italy

[6] CSIC IDIBAPS, Inst Invest Biomed Barcelona, Dept Neurochem & Neuropharmacol, Rossello 161, Barcelona 08036, Spain

[7] Ctr Invest Biomed Red Salud Mental CIBERSAM, Barcelona, Spain

关键词: 5-HT2B receptor;    5-HT1A receptor;    Dopamine release;    5-HT firing;    Mesocorticolimbic dopamine system;    Dorsal raphe nucleus;   

DOI  :  10.1016/j.neuropharm.2017.04.001

来源: Elsevier

【 摘 要 】

Recent studies have shown that serotonin(2B) 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-HT(1A)Rs 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-HTSAR (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 mu M), 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 mu g/0.2 mu l). 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. (C) 2017 Elsevier Ltd. All rights reserved.

【 授权许可】

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