title: Effect of the multimodal acting antidepressant vortioxetine on rat hippocampal plasticity and recognition memory.
abstract: Depression is frequently associated with cognitive disturbances. Vortioxetine is a multimodal acting antidepressant that functions as a 5-HT3 and 5-HT7 and 5-HT1D receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist and inhibitor of the 5-HT transporter. Given its pharmacological profile, the present study was undertaken to determine whether vortioxetine could modulate several preclinical parameters known to be involved in cognitive processing. In the dorsal hippocampus of anaesthetized rats, the high-frequency stimulation of the Schaffer collaterals provoked a stable long-term potentiation (LTP) of ~25%. Interestingly, vortioxetine (10mg/kg, i.p.) counteracted the suppressant effect of elevated platform stress on hippocampal LTP induction. In the novel object recognition test, vortioxetine (10mg/kg, i.p.) increased the time spent exploring the novel object during the retention test and this pro-cognitive effect was prevented by the partial 5-HT3 receptor agonist SR57227 (1mg/kg, i.p.). Finally, compared to fluoxetine, sustained administration of vortioxetine (5mg/kg/day, s.c.) induced a rapid increase of cell proliferation in the hippocampal dentate gyrus. In summary, vortioxetine prevented the effect of stress on hippocampal LTP, increased rapidly hippocampal cell proliferation and enhanced short-term episodic memory, via, at least in part, its 5-HT3 receptor antagonism. Taken together, these preclinical data suggest that the antidepressant vortioxetine may have a beneficial effect on human cognitive processes.
authors.affiliation: INSERM U846, Stem Cell and Brain Research Institute, Université Lyon 1, Lyon, F-69008, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Bétry
authors.affiliation: INSERM U846, Stem Cell and Brain Research Institute, Université Lyon 1, Lyon, F-69008, France.
authors.forename: Adeline
authors.initials: A
authors.lastname: Etiévant
authors.affiliation: Neuropharmacological Research, Lundbeck Research USA, 215 College Road, Paramus, NJ 07652, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Pehrson
authors.affiliation: Neuropharmacological Research, Lundbeck Research USA, 215 College Road, Paramus, NJ 07652, USA.
authors.forename: Connie
authors.initials: C
authors.lastname: Sánchez
authors.affiliation: INSERM U846, Stem Cell and Brain Research Institute, Université Lyon 1, Lyon, F-69008, France. Electronic address: nasser.haddjeri@inserm.fr.
authors.forename: Nasser
authors.initials: N
authors.lastname: Haddjeri
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D015331:Cohort Studies; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005473:Fluoxetine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D061212:Memory, Episodic; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology*; D016601:RNA-Binding Proteins / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects* / Q000502:physiology; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology*; D013315:Stress, Psychological / Q000188:drug therapy / Q000503:physiopathology; D013440:Sulfides / Q000494:pharmacology*; D000078784:Vortioxetine
chemical_list: D000928:Antidepressive Agents; D010879:Piperazines; D016601:RNA-Binding Proteins; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; C482440:Sert1 protein, rat; D013440:Sulfides; D005473:Fluoxetine; D000078784:Vortioxetine
keywords: Antidepressant; LTP; Memory; Neurogenesis; Novel object recognition; Vortioxetine