Journal of Molecular Neuroscience

, Volume 55, Issue 2, pp 552–560 | Cite as

Effects of the Anti-Multiple Sclerosis Immunomodulator Laquinimod on Anxiety and Depression in Rodent Behavioral Models

  • Irit Gil-Ad
  • Ben H. Amit
  • Liat Hayardeni
  • Igor Tarasenko
  • Michal Taler
  • Ravit Uzan Gueta
  • Abraham Weizman
Article

Abstract

Laquinimod is a novel oral immunomodulatory drug for the treatment of multiple sclerosis (MS). Considering the frequent co-morbidity of MS with anxiety and depression, we sought to assess the antidepressant and anxiolytic effects of laquinimod in mouse models. Laquinimod (0.5–25 mg/kg), fluoxetine (10 mg/kg) or vehicle were administered for 4–14 days to adult Balb/c mice, followed by behavioral tests and brain BDNF analysis. Following a 4-day administration of laquinimod (5 and 25 mg/kg), an increase in motivated behavior was observed in the forced swim test (p < 0.01 vs. controls). In the open field test, laquinimod (0.5–5 mg/kg), but not fluoxetine, significantly increased motility (p < 0.05), whereas both decreased anxiety behavior (p < 0.01), evident only for laquinimod (5 mg/kg) in the elevated plus maze (p < 0.05). Following 7 days of administration, both drugs decreased anxiety behavior in the elevated plus maze and marble burying tests (p < 0.001 and p < 0.02, respectively). After 14 days, only laquinimod (5 mg/kg) demonstrated anxiolytic efficacy in the open field test (p < 0.05), with evidence of increased BDNF in response to 5–25 mg/kg in the hippocampus, but not frontal cortex (p < 0.05). In conclusion, laquinimod may possess anxiolytic and antidepressant effects, possibly associated with hippocampal BDNF increase, offering promise for MS patients suffering from psychiatric co-morbidity.

Keywords

Laquinimod Fluoxetine Brain-derived neurotrophic factor (BDNF) Multiple sclerosis Anxiety Depression 

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Irit Gil-Ad
    • 1
    • 2
  • Ben H. Amit
    • 2
    • 3
  • Liat Hayardeni
    • 4
  • Igor Tarasenko
    • 1
    • 2
  • Michal Taler
    • 1
    • 2
  • Ravit Uzan Gueta
    • 1
    • 2
  • Abraham Weizman
    • 1
    • 2
    • 3
  1. 1.Laboratory of Biological Psychiatry, Felsenstein Medical Research CenterRabin Medical CenterPetah TikvaIsrael
  2. 2.Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael
  3. 3.Research UnitGeha Mental Health CenterPetah TikvaIsrael
  4. 4.Teva Pharmaceutical CorporationPetah TikvaIsrael

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