Examining the Efficacy of Montelukast in Behavioral Models in Rats

Introduction. Accumulative data suggests that inflammation contributes to the pathophysiology of mental disorders. Leukotrienes (LTs) are inflammatory mediators that strongly affect the function of tissues including the brain; almost nothing is known about their involvement in the pathophysiology of mental illnesses. Leukotrienes-modifying agents (LTMAs) are medications used for the treatment of inflammation-and-allergy-related disorders. Circumstantial evidence has suggested that treatment with LTMAs, such as montelukast (MTK), may induce various adverse neuropsychiatric events in humans.

Objective. Examine the behavioral effects and inflammatory mediator levels of chronic MTK treatment in male and female.

Methods. Rats were exposed to a chronic-unpredictable-mild-stress (CUMS) protocol for four weeks. Thereafter, rats were treated once daily, for two weeks, with either vehicle or 5 or 20mg/kg MTK. During the protocol, behavior tests were conducted and brain regions were evaluated for inflammatory mediators: interleukin (IL)-6, prostaglandin (PG)-E2 and tumor necrosis factor (TNF)-α.

Results. MTK did not induce negative behavioral phenotypes in control or CUMS-subjected rats, except for an aggression-inducing effect of MTK in males. However, positive behavioral outcomes were observed: reduction in aggressive behavior in females, reduction in manic/hyperactive-like behavior in males; and, increase sucrose consumption of the CUMS-induced males. Furthermore, in control males, MTK increased IL-6 levels in the HT and TNF-α levels in the FC. While, in control females, MTK decreased IL-6 and TNF-α levels in all brain regions.

Conclusion. Overall, the results indicate that MTK may actually be associated with some beneficial behavioral outcomes. Moreover, the results shows that MTK differentially affects male vs. female rats.