title: 5-HT(2B) receptors are required for serotonin-selective antidepressant actions.
abstract: The therapeutic effects induced by serotonin-selective reuptake inhibitor (SSRI) antidepressants are initially triggered by blocking the serotonin transporter and rely on long-term adaptations of pre- and post-synaptic receptors. We show here that long-term behavioral and neurogenic SSRI effects are abolished after either genetic or pharmacological inactivation of 5-HT(2B) receptors. Conversely, direct agonist stimulation of 5-HT(2B) receptors induces an SSRI-like response in behavioral and neurogenic assays. Moreover, the observation that (i) this receptor is expressed by raphe serotonergic neurons, (ii) the SSRI-induced increase in hippocampal extracellular serotonin concentration is strongly reduced in the absence of functional 5-HT(2B) receptors and (iii) a selective 5-HT(2B) agonist mimics SSRI responses, supports a positive regulation of serotonergic neurons by 5-HT(2B) receptors. The 5-HT(2B) receptor appears, therefore, to positively modulate serotonergic activity and to be required for the therapeutic actions of SSRIs. Consequently, the 5-HT(2B) receptor should be considered as a new tractable target in the combat against depression.
authors.affiliation: UMR-S839 INSERM, Paris, France.
authors.forename: S L
authors.initials: SL
authors.lastname: Diaz
authors.forename: S
authors.initials: S
authors.lastname: Doly
authors.forename: N
authors.initials: N
authors.lastname: Narboux-Nême
authors.forename: S
authors.initials: S
authors.lastname: Fernández
authors.forename: P
authors.initials: P
authors.lastname: Mazot
authors.forename: S M
authors.initials: SM
authors.lastname: Banas
authors.forename: K
authors.initials: K
authors.lastname: Boutourlinsky
authors.forename: I
authors.initials: I
authors.lastname: Moutkine
authors.forename: A
authors.initials: A
authors.lastname: Belmer
authors.forename: A
authors.initials: A
authors.lastname: Roumier
authors.forename: L
authors.initials: L
authors.lastname: Maroteaux
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000009:adverse effects; D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D005106:Exploratory Behavior / Q000187:drug effects; D005473:Fluoxetine / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D007035:Hypothermia / Q000139:chemically induced; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017551:Microdialysis; D055495:Neurogenesis / Q000187:drug effects*; D011930:Reaction Time / Q000187:drug effects; D044403:Receptor, Serotonin, 5-HT2B / Q000172:deficiency / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000172:deficiency / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000009:adverse effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013997:Time Factors; D014157:Transcription Factors / Q000172:deficiency
chemical_list: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D001973:Bromodeoxyuridine; D005473:Fluoxetine; D019394:Ki-67 Antigen; D044403:Receptor, Serotonin, 5-HT2B; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D014157:Transcription Factors; C484684:Fev protein, mouse