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Objective: Montelukast is a leukotriene receptor antagonist used for the treatment of chronic asthma and to relieve symptoms of seasonal allergies. The Food and Drug Administration Committee issued a warning with regard to the correlation between suicide, psychiatric symptoms and the use of Montelukast. This report is entirely based on information from case reports on asthma patients. However, there may be a link between asthma and depression, which is the most important risk factor for suicide. Therefore, the increased suicide rate reported in asthma patients may not be dependent on Montelukast use. Likewise, a retrospective evaluation of clinical data found no elevated risk of suicide in patients treated with Montelukast. Therefore, there is a controversy about the proposed association. The aim of present study is to research the effect of Montelukast treatment on depressive and anxiety behaviors in healthy rats.
Methods: Twenty-two female Wistar albino rats (150–200 g) were used in this research. The rats were divided into two groups: a Montelukast-treated group (n=10) and a saline-treated control group (n=10). Montelukast was intraperitoneally injected at a dose of 10mg/100µl/kg for 10 days. A forced swimming test and open field test was performed on day 10 to evaluate the depressive and anxiety behaviors of rats. In the forced swimming test, rats were placed individually in a cylindrical tank (30cm width × 50cm height containing 25cm of water at 24±1oC) for 6min. In the open field test, rats were placed in a box (100×100×25cm) containing 16 equal squares for 5min. In the forced swimming test, total mobility time was determined as the sum of the time spent in climbing and swimming behaviors. The rats were judged to be immobile when they remained in the water without struggling. In the open field analyses, the time spent in the center squares, the time spent grooming, as well as the number of rearing, defecation and line crossing, were determined. The drugtreated group was compared to the control group. A Student’s two-tailed t-test and Mann-Whitney U test were used for parametric and non-parametric data, respectively. Data were expressed as means with±standard error of the mean.
Results: Montelukast treatment induced depressive behavioral responses, with a significant increase in immobility time (Montelukast: 187±9 s versus 125±4 s for the control, p<0.001) and decrease in swimming time (Montelukast: 34±7 s versus 90±7 s for the control, p<0.001) and total mobility time (Montelukast: 52±9 s versus 110±13 s for the control, p<0.001). Montelukast treatment did not change any data regarding anxiety behaviors.
Conclusion: These results reveal that Montelukast treatment induced depressive behaviors in healthy rats, but it did not cause anxiety behaviors. These findings support the warning with regard to the correlation between suicide, psychiatric symptoms and the use of Montelukast. However, further studies are needed to test the effects of Montelukast on depression and anxiety in rats with experimentallyinduced asthma, and to elucidate the mechanism of the effects of Montelukast.