High-Dose of oral Montelukast Induces Monoamines Depletion and brain-Derived Neurotrophic Factor BDNF Upregulation in male Rat's Brain

Background: Montelukast, a leukotriene D4 antagonist used for asthma and allergic rhinitis, has been increasingly linked to neuropsychiatric effects, including mood disorders and suicidality. Its impact on central monoamine neurotransmitters and neurotrophic factors remains unclear.Objective: This study aimed to evaluate the impact of montelukast on monoamine neurotransmitters and brain-derived neurotrophic factor (BDNF) in rats, in conjunction with a histological analysis of brain tissue. Methods: Thirty-five male albino rats were randomly assigned to five groups (n=7 each): a negative control, a positive control given reserpine (0.2 mg/kg, i.p.), and three groups receiving oral montelukast at 5, 10, and 20 mg/kg/day for 14 days. Monoamines (dopamine, serotonin, norepinephrine) and BDNF were measured using ELISA. Histopathological changes were examined with H&E staining. Results: Montelukast treatment resulted in a dose-dependent decrease in dopamine, serotonin, and norepinephrine, akin to the monoamine depletion caused by reserpine. Notably, BDNF levels were markedly increased in both the reserpine group and the high-dose montelukast group (20 mg/kg). Histological analysis demonstrated normal neuronal morphology at low dose, but higher doses (10 and 20 mg/kg/day) resulted in moderate vascular congestion and neuronal edema without necrosis.Conclusion: Montelukast causes considerable monoamine depletion and a counterintuitive increase in BDNF at elevated dosages, with initial neurotoxic histopathological alterations in the brain tissues of male rats. Further detailed studies are warranted to determine whether these modifications contribute to the neuropsychiatric side effects observed in clinical environments.