title: Effects of the anti-multiple sclerosis immunomodulator laquinimod on anxiety and depression in rodent behavioral models.
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.
authors: Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel.
authors: Irit
authors: I
authors: Gil-Ad
authors: Ben H
authors: BH
authors: Amit
authors: Liat
authors: L
authors: Hayardeni
authors: Igor
authors: I
authors: Tarasenko
authors: Michal
authors: M
authors: Taler
authors: Ravit Uzan
authors: RU
authors: Gueta
authors: Abraham
authors: A
authors: Weizman
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D003863:Depression / Q000188:drug therapy*; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use; D006624:Hippocampus / Q000378:metabolism; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008807:Mice, Inbred BALB C; D015363:Quinolones / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D007155:Immunologic Factors; D015363:Quinolones; D005473:Fluoxetine; C476223:laquinimod