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

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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.

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Authors and Affiliations

  1. Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel

    Irit Gil-Ad, Igor Tarasenko, Michal Taler, Ravit Uzan Gueta & Abraham Weizman

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Irit Gil-Ad, Ben H. Amit, Igor Tarasenko, Michal Taler, Ravit Uzan Gueta & Abraham Weizman

  3. Research Unit, Geha Mental Health Center, 1 Helsinky St., Petah Tikva, Israel, 49100

    Ben H. Amit & Abraham Weizman

  4. Teva Pharmaceutical Corporation, Petah Tikva, Israel

    Liat Hayardeni

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  1. Irit Gil-Ad
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  2. Ben H. Amit
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  4. Igor Tarasenko
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Correspondence to Ben H. Amit.

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Irit Gil-Ad and Ben H. Amit are equal contributors and co-authors of this manuscript.

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Gil-Ad, I., Amit, B.H., Hayardeni, L. et al. Effects of the Anti-Multiple Sclerosis Immunomodulator Laquinimod on Anxiety and Depression in Rodent Behavioral Models. J Mol Neurosci 55, 552–560 (2015). https://doi.org/10.1007/s12031-014-0387-3

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  • DOI: https://doi.org/10.1007/s12031-014-0387-3

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