title: Mice lacking the serotonin 5-HT2B receptor as an animal model of resistance to selective serotonin reuptake inhibitors antidepressants.
abstract: Depressive disorders are among the most prevalent neuropsychiatric dysfunctions worldwide, with high rates of resistance to antidepressant treatment. Genetic factors clearly contribute to the manifestation of depression as well as to the response to antidepressants. Transgenic mouse models appear as seminal tools to disentangle this complex disorder. Here, we analyzed new key aspects of the phenotype of knock-out mice for the gene encoding the serotonin 2B receptor (Htr(2B)(-/-)), including basal phenotype, ability to develop a depressive-like phenotype upon chronic isolation, and effect of chronic exposure to fluoxetine on chronically stressed Htr(2B)(-/-) mice. We find, here, that Htr(2B)(-/-) mice display an antidepressant-like phenotype, which includes reduced latency to feed in the novelty suppressed feeding test, basal increase in hippocampal BDNF levels, no change in TrkB and p75 protein levels, and an increased preference for sucrose consumption compared to wild type (Htr(2B)(+/+)) mice. Nevertheless, we show that these mice can develop depressive-like behaviors when socially isolated during four weeks. Selective serotonin reuptake inhibitors (SSRI) have been previously shown to be ineffective in non-stressed Htr(2B)(-/-) mice. We evaluated, here, the effects of the SSRI fluoxetine in chronically stressed Htr(2B)(-/-) mice and similarly no behavioral or plastic effect was induced by this antidepressant. All together, these results highlight the suitability to study resistance to SSRI antidepressants of this mouse model displaying panoply of conditions among which behavioral, neurotrophic and plastic causative factors can be analyzed.
authors.affiliation: INSERM UMR-S 839, F75005 Paris, France; Université Pierre et Marie Curie, F75005 Paris, France; Institut du Fer à Moulin, F75005 Paris, France.
authors.forename: Silvina Laura
authors.initials: SL
authors.lastname: Diaz
authors.affiliation: INSERM UMR-S 839, F75005 Paris, France; Université Pierre et Marie Curie, F75005 Paris, France; Institut du Fer à Moulin, F75005 Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Narboux-Nême
authors.affiliation: INSERM UMR-S 839, F75005 Paris, France; Université Pierre et Marie Curie, F75005 Paris, France; Institut du Fer à Moulin, F75005 Paris, France.
authors.forename: Katia
authors.initials: K
authors.lastname: Boutourlinsky
authors.affiliation: INSERM UMR-S 839, F75005 Paris, France; Université Pierre et Marie Curie, F75005 Paris, France; Institut du Fer à Moulin, F75005 Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Doly
authors.affiliation: INSERM UMR-S 839, F75005 Paris, France; Université Pierre et Marie Curie, F75005 Paris, France; Institut du Fer à Moulin, F75005 Paris, France. Electronic address: luc.maroteaux@upmc.fr.
authors.forename: Luc
authors.initials: L
authors.lastname: Maroteaux
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D008124:Locomotion / Q000187:drug effects / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D011930:Reaction Time / Q000187:drug effects; D044403:Receptor, Serotonin, 5-HT2B / Q000172:deficiency* / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D013550:Swimming / Q000523:psychology
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D044403:Receptor, Serotonin, 5-HT2B; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors
keywords: 5-HT(2B); Chronic stress; Depression; Receptor; SSRI antidepressants; Serotonin