Positive regulation of raphe serotonin neurons by serotonin 2B receptors
Serotonin is a neurotransmitter involved in many psychiatric diseases. In humans, a lack of 5-HT 2B receptors is associated with serotonin-dependent phenotypes, including impulsivity and suicidality. A lack of 5-HT 2B receptors in mice eliminates the effects of molecules that directly target seroton...
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Nature Publishing Group
2018
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| 024 | 7 | |2 cas |a 1 [5 (2 thienylmethoxy) 3 indolyl] 2 propanamine, 160521-72-2; 4 iodo 2,5 dimethoxyamphetamine, 64584-34-5; fluoxetine, 54910-89-3, 56296-78-7, 59333-67-4; midomafetamine, 42542-10-9; 2 dipropylamino 8 hydroxytetralin, 78950-78-4; 3,4 methylenedioxyamphetamine, 4764-17-4; 1-(5-(2-thenyloxy)-1H-indol-3-yl)propan-2-amine; 3,4-Methylenedioxyamphetamine; 4-iodo-2,5-dimethoxyphenylisopropylamine; 8-Hydroxy-2-(di-n-propylamino)tetralin; Amphetamines; Fev protein, mouse; Fluoxetine; Indoles; Receptor, Serotonin, 5-HT2B; Serotonin 5-HT2 Receptor Agonists; Thiophenes; Transcription Factors | |
| 040 | |a Scopus |b spa |c AR-BaUEN |d AR-BaUEN | ||
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| 100 | 1 | |a Belmer, A. | |
| 245 | 1 | 0 | |a Positive regulation of raphe serotonin neurons by serotonin 2B receptors |
| 260 | |b Nature Publishing Group |c 2018 | ||
| 270 | 1 | 0 | |m Maroteaux, L.; INSERM UMR-S 839France; email: luc.maroteaux@upmc.fr |
| 506 | |2 openaire |e Política editorial | ||
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| 520 | 3 | |a Serotonin is a neurotransmitter involved in many psychiatric diseases. In humans, a lack of 5-HT 2B receptors is associated with serotonin-dependent phenotypes, including impulsivity and suicidality. A lack of 5-HT 2B receptors in mice eliminates the effects of molecules that directly target serotonergic neurons including amphetamine derivative serotonin releasers, and selective serotonin reuptake inhibitor antidepressants. In this work, we tested the hypothesis that 5-HT 2B receptors directly and positively regulate raphe serotonin neuron activity. By ex vivo electrophysiological recordings, we report that stimulation by the 5-HT 2B receptor agonist, BW723C86, increased the firing frequency of serotonin Pet1-positive neurons. Viral overexpression of 5-HT 2B receptors in these neurons increased their excitability. Furthermore, in vivo 5-HT 2B -receptor stimulation by BW723C86 counteracted 5-HT 1A autoreceptor-dependent reduction in firing rate and hypothermic response in wild-type mice. By a conditional genetic ablation that eliminates 5-HT 2B receptor expression specifically and exclusively from Pet1-positive serotonin neurons (Htr2b 5-HTKO mice), we demonstrated that behavioral and sensitizing effects of MDMA (3,4-methylenedioxy-methamphetamine), as well as acute behavioral and chronic neurogenic effects of the antidepressant fluoxetine, require 5-HT 2B receptor expression in serotonergic neurons. In Htr2b 5-HTKO mice, dorsal raphe serotonin neurons displayed a lower firing frequency compared to control Htr2b lox/lox mice as assessed by in vivo extracellular recordings and a stronger hypothermic effect of 5-HT 1A -autoreceptor stimulation was observed. The increase in head-twitch response to DOI (2,5-dimethoxy-4-iodoamphetamine) further confirmed the lower serotonergic tone resulting from the absence of 5-HT 2B receptors in serotonin neurons. Together, these observations indicate that the 5-HT 2B receptor acts as a direct positive modulator of serotonin Pet1-positive neurons in an opposite way as the known 5-HT 1A -negative autoreceptor. © 2018 American College of Neuropsychopharmacology. |l eng | |
| 593 | |a INSERM UMR-S 839, Paris, 75005, France | ||
| 593 | |a Sorbonne Universités, UPMC Univ Paris 6, Paris, 75005, France | ||
| 593 | |a Institut du Fer À Moulin, Paris, 75005, France | ||
| 593 | |a Translational Research Institute, Queensland University of Technology, Brisbane, QLD 4059, Australia | ||
| 593 | |a Instituto de Biología Celular y Neurociencia, Fac. de Cs. Exactas, Químicas y Naturales, Universidad de Morón, UBA-CONICET, Paraguay 2155, 3o piso Argentina, Buenos Aires, C1121ABG, Argentina | ||
| 593 | |a Research Center on Animal Cognition, Center for Integrative Biology, Toulouse, 31062, France | ||
| 593 | |a Université Paul Sabatier, Toulouse, 31062, France | ||
| 593 | |a UMR5169 CNRS, Toulouse, 31062, France | ||
| 593 | |a IPMC - CNRS UMR7275 660 Route des Lucioles Sophia-Antipolis, Valbonne, 06560, France | ||
| 593 | |a Université Clermont Auvergne, INSERM, NEURO-DOL, Clermont-Ferrand, 63000, France | ||
| 593 | |a Department of Biology and Center for Tissue Regeneration and Engineering at Dayton (TREND), University of Dayton, Dayton, OH, United States | ||
| 593 | |a Dept. Fundamental Neurosciences (DNF) the University of Lausanne, Lausanne, Switzerland | ||
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