Publications

Latest publication 10/30/2013

Antidepressant and anxiolytic potential of the multimodal antidepressant vortiox

Vortioxetine (Lu AA21004) is an investigational novel antidepressant with multimodal activity that functions as a 5-HT3, 5-HT7 and 5-HT1D receptor...

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    [title] => Antidepressant and anxiolytic potential of the multimodal antidepressant vortiox
    [paragraph] => Antidepressant and anxiolytic potential of the multimodal antidepressant vortioxetine (Lu AA21004) assessed by behavioural and neurogenesis outcomes in mice
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Authors
Jean-Philippe Guillouxa, Indira Mendez-Davida, Alan Pehrsonb, Bruno P. Guiard et al.

 Lab
Univ. Paris-Sude, France - Lundbeck Research, USA
Journal
Neuropharmacology Volume 73
Abstract
Vortioxetine (Lu AA21004) is an investigational novel antidepressant with multimodal activity that functions as a 5-HT3, 5-HT7 and 5-HT1D receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist and inhibitor of the 5-HT transporter in vitro. Here we explore its anxiolytic and antidepressant potential in adult mice. Vortioxetine was assessed in BalB/cJ@RJ mice using the open-field and forced-swim tests (acute: p.o. 1 h, repeated: daily p.o. 21 days), and in 129S6/SvEvTac mice using the novelty suppressed feeding paradigm (acute: p.o. 1 h, sustained: daily p.o. 14 or 21 days). Fluoxetine and diazepam were controls. Acute and repeated dosing of vortioxetine produced more pronounced anxiolytic- and antidepressant-like activities than fluoxetine. Vortioxetine significantly increased cell proliferation and cell survival and stimulated maturation of immature granule cells in the subgranular zone of the dentate gyrus of the hippocampus after 21 days of treatment. After 14 days, a high dose of vortioxetine increased dendritic length and the number of dendrite intersections, suggesting that vortioxetine accelerates the maturation of immature neurons. Vortioxetine displays an antidepressant and anxiolytic profile following repeated administration associated with increased neurogenesis at several stages. Vortioxetine effects were observed at low levels of 5-HT transporter occupancy, suggesting an alternative mechanism of action to 5-HT reuptake inhibition.
BIOSEB Instruments Used
Tail Suspension Test - Wireless (BIO-TST5),Forced Swimming Test: New FST DUAL SENSOR (BIO-FST-DSM)
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Experiment manager, analysis module, replay possibilities and the TYC algorithm are some of the features that make FST DUAL SENSOR a very innovative and easy to use instrument for both mice or rats studies (up to 4 animals can be tested at a time), based on the famous Porsolt Test, or "behavioral despair" test

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