Belmer, A.; Quentin, E.; Diaz, S.L.; Guiard, B.P.; Fernandez, S.P.; Doly, S.; Banas, S.M.; Pitychoutis, P.M.; Moutkine, I.; Muzerelle, A.; Tchenio, A.; Roumier, A.; Mameli, M.; Maroteaux, L. "Positive regulation of raphe serotonin neurons by serotonin 2B receptors" (2018) Neuropsychopharmacology. 43(7):1623-1632
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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.


Documento: Artículo
Título:Positive regulation of raphe serotonin neurons by serotonin 2B receptors
Autor:Belmer, A.; Quentin, E.; Diaz, S.L.; Guiard, B.P.; Fernandez, S.P.; Doly, S.; Banas, S.M.; Pitychoutis, P.M.; Moutkine, I.; Muzerelle, A.; Tchenio, A.; Roumier, A.; Mameli, M.; Maroteaux, L.
Filiación:INSERM UMR-S 839, Paris, 75005, France
Sorbonne Universités, UPMC Univ Paris 6, Paris, 75005, France
Institut du Fer À Moulin, Paris, 75005, France
Translational Research Institute, Queensland University of Technology, Brisbane, QLD 4059, Australia
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
Research Center on Animal Cognition, Center for Integrative Biology, Toulouse, 31062, France
Université Paul Sabatier, Toulouse, 31062, France
UMR5169 CNRS, Toulouse, 31062, France
IPMC - CNRS UMR7275 660 Route des Lucioles Sophia-Antipolis, Valbonne, 06560, France
Université Clermont Auvergne, INSERM, NEURO-DOL, Clermont-Ferrand, 63000, France
Department of Biology and Center for Tissue Regeneration and Engineering at Dayton (TREND), University of Dayton, Dayton, OH, United States
Dept. Fundamental Neurosciences (DNF) the University of Lausanne, Lausanne, Switzerland
Palabras clave:1 [5 (2 thienylmethoxy) 3 indolyl] 2 propanamine; 4 iodo 2,5 dimethoxyamphetamine; autoreceptor; fluoxetine; midomafetamine; serotonin 1A receptor; serotonin 2B receptor; 1-(5-(2-thenyloxy)-1H-indol-3-yl)propan-2-amine; 2 dipropylamino 8 hydroxytetralin; 3,4 methylenedioxyamphetamine; 4-iodo-2,5-dimethoxyphenylisopropylamine; amphetamine derivative; Fev protein, mouse; fluoxetine; indole derivative; serotonin 2 agonist; serotonin 2B receptor; thiophene derivative; transcription factor; animal behavior; animal cell; animal experiment; animal tissue; Article; brain electrophysiology; brain slice; brain synaptosome; comparative study; controlled study; dorsal raphe nucleus; ex vivo study; firing rate; forced swim test; gene overexpression; head twitch; hypothermia; immobility time; locomotion; male; mouse; nerve cell excitability; nerve stimulation; nonhuman; prepulse inhibition; priority journal; regulatory mechanism; serotoninergic nerve cell; subgranular zone; action potential; animal; body temperature; central nervous system sensitization; drug effect; female; genetics; knockout mouse; nervous system development; physiology; raphe nucleus; serotoninergic nerve cell; transgenic mouse; 3,4-Methylenedioxyamphetamine; 8-Hydroxy-2-(di-n-propylamino)tetralin; Action Potentials; Amphetamines; Animals; Body Temperature; Central Nervous System Sensitization; Female; Fluoxetine; Indoles; Male; Mice; Mice, Knockout; Mice, Transgenic; Neurogenesis; Prepulse Inhibition; Raphe Nuclei; Receptor, Serotonin, 5-HT2B; Serotonergic Neurons; Serotonin 5-HT2 Receptor Agonists; Thiophenes; Transcription Factors
Página de inicio:1623
Página de fin:1632
Título revista:Neuropsychopharmacology
Título revista abreviado:Neuropsychopharmacology
CAS: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


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---------- APA ----------
Belmer, A., Quentin, E., Diaz, S.L., Guiard, B.P., Fernandez, S.P., Doly, S., Banas, S.M.,..., Maroteaux, L. (2018) . Positive regulation of raphe serotonin neurons by serotonin 2B receptors. Neuropsychopharmacology, 43(7), 1623-1632.
---------- CHICAGO ----------
Belmer, A., Quentin, E., Diaz, S.L., Guiard, B.P., Fernandez, S.P., Doly, S., et al. "Positive regulation of raphe serotonin neurons by serotonin 2B receptors" . Neuropsychopharmacology 43, no. 7 (2018) : 1623-1632.
---------- MLA ----------
Belmer, A., Quentin, E., Diaz, S.L., Guiard, B.P., Fernandez, S.P., Doly, S., et al. "Positive regulation of raphe serotonin neurons by serotonin 2B receptors" . Neuropsychopharmacology, vol. 43, no. 7, 2018, pp. 1623-1632.
---------- VANCOUVER ----------
Belmer, A., Quentin, E., Diaz, S.L., Guiard, B.P., Fernandez, S.P., Doly, S., et al. Positive regulation of raphe serotonin neurons by serotonin 2B receptors. Neuropsychopharmacology. 2018;43(7):1623-1632.