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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Publicado:	2018
Materias:	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 indole derivative serotonin 2 agonist 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 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
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0893133X_v43_n7_p1623_Belmer http://hdl.handle.net/20.500.12110/paper_0893133X_v43_n7_p1623_Belmer
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paper:paper_0893133X_v43_n7_p1623_Belmer2023-06-08T15:47:30Z Positive regulation of raphe serotonin neurons by serotonin 2B receptors 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 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. 2018 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0893133X_v43_n7_p1623_Belmer http://hdl.handle.net/20.500.12110/paper_0893133X_v43_n7_p1623_Belmer
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 Positive regulation of raphe serotonin neurons by serotonin 2B receptors
topic_facet	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
description	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.
title	Positive regulation of raphe serotonin neurons by serotonin 2B receptors
title_short	Positive regulation of raphe serotonin neurons by serotonin 2B receptors
title_full	Positive regulation of raphe serotonin neurons by serotonin 2B receptors
title_fullStr	Positive regulation of raphe serotonin neurons by serotonin 2B receptors
title_full_unstemmed	Positive regulation of raphe serotonin neurons by serotonin 2B receptors
title_sort	positive regulation of raphe serotonin neurons by serotonin 2b receptors
publishDate	2018
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0893133X_v43_n7_p1623_Belmer http://hdl.handle.net/20.500.12110/paper_0893133X_v43_n7_p1623_Belmer
_version_	1768546403304341504

Positive regulation of raphe serotonin neurons by serotonin 2B receptors

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