Abstract: AIM: To investigate the effects of montelukast on learning memory and cholinergic system in model mice induced by scopolamine.METHODS: Mice were randomly divided into 5 groups: vehicle plus vehicle (Veh+Veh), scopolamine plus vehicle(Scop+Veh), scopolamine plus donepezil (Scop+Done 2.0 mg/kg), scopolamine plus montelukast 1.0 mg·kg^-1·d^-1 (Scop+Mon 1.0 mg/kg) and scopolamine plus montelukast 2.0 mg·kg^-1·d^-1 (Scop+Mon 2.0 mg/kg). The drugs were intragastrically administered for 14 consecutive days at 0.5 h after intraperitoneal injection with scopolamine (1.0 mg·kg^-1·d^-1) in mice. Mice were submitted to Morris water maze (MWM) test and Y maze test. Changes in cholinergic system reactivity were also examined by measuring the acetylcholine and acetylcholinesterase in the hippocampus and cortex.RESULTS: Scopolamine injection induced learning memory impairment in the MWM test and Y maze test and severe decrease of cholinergic system reactivity, as indicated by reduced acetylcholine levels and increased acetylcholinesterase activity. Daily administration of montelukast significantly decreased the escape latency times to the platform during acquisition trials, increased the times in target quadrant and the number of crossing times in the probe trial, and times of correct response in Y maze test. This treatment also significantly decreased TChE activity and increased ACh levels in hippocampus and cortex.CONCLUSION: Montelukast demonstrates a significant neuroprotective effect against scopolamine-induced learning memory impairment resulting from Ach elevation through decreasing TChE activity.

Key words: montelukast, scopolamine, learning-memory, acetylcholine, acetylcholinesterase