Investigation of the relationship between chronic montelukast treatment, asthma and depression‑like behavior in mice

Abstract

In 2008, the Food and Drug Administration of the US issued a warning about the neuropsychiatric side effects of montelukast. Previous clinical studies on montelukast have reported conflicting results and, to the best of our knowledge, no experimental studies concerning these side effects had been conducted. In the current study, the effect of montelukast on depression-like behavior in an ovalbumin (OVA)-induced mouse model was investigated. A total of 3 OVA challenges were applied at 2 week intervals for the persistence of asthma. Depression-like behavior was assessed using forced swim tests following each challenge and locomotor activities were evaluated using open field tests. At the end of the current study, plasma montelukast concentrations were measured and the development of asthma and effect of montelukast treatment were histopathologically examined. Inflammation scores that were increased in the OVA mice following all challenges were indicated to be reduced by montelukast treatment. The immobility time of mice increased beginning with the first challenge and this was also reduced by montelukast treatment. Montelukast administration to the control mice did not alter immobility times. Moreover, motor activity of the OVA and montelukast-treated mice were not altered. The results indicated there was no association between chronic montelukast treatment and depression. Furthermore, the chronic administration of montelukast to non-asthmatic mice did not increase immobility. However, depressive behavior increased at all time points in the OVA mice. These results indicated that chronic montelukast treatment is not associated with depression-like behavior and confirmed the association between asthma and depression. Further studies are required to provide an improved understanding of the neuropsychiatric side effects of montelukast.

Chronic allergic lung inflammation negatively influences neurobehavioral outcomes in mice

“…5 B), suggesting changes in depression-like behaviors. The FST was also performed following sensitization to examine the long-term effects of chronic allergic lung inflammation on depression-like behavior [ 23 ]. Immobility times between the PBS group and HDM group in the FST were not significantly increased in during the total 6-min trial or during the final 3-6 min time periods (Fig.…”

Cycloastragenol alleviates airway inflammation in asthmatic mice by inhibiting autophagy

“…10023418, SCRC) for 5 min twice, according to the manufacturer's instructions. Inflammation score of H&E staining ( 33 ) and the percentage of PAS + bronchial cells ( 34 ) were determined as previously described.…”

Leukotriene receptor antagonists and risk of neuropsychiatric events in children, adolescents and young adults: a self-controlled case series

“…Moreover, in asthma patients, the therapeutic effects of montelukast are seen one day after starting the medication, continuously improving over 12 weeks [18]. Interestingly, in mice models of asthma, montelukast treatment did not lead to depression-like behaviour, while mice that received saline showed symptoms of depression [19]. Therefore, the possible risk of LTRA-associated NPEs transiently may increase during the first two weeks and later decrease as asthma/AR symptoms are controlled.…”