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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)552-560
Number of pages9
JournalJournal of Molecular Neuroscience
Volume55
Issue number2
DOIs
StatePublished - Feb 2014

Keywords

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

Fingerprint

Dive into the research topics of 'Effects of the Anti-Multiple Sclerosis Immunomodulator Laquinimod on Anxiety and Depression in Rodent Behavioral Models'. Together they form a unique fingerprint.

Cite this