Lamotrigine enhances the neuroprotective effects of memantine on aluminum chloride-induced behavioral changes in rats

Abstract

Background and aimAlzheimer's disease (AD) is the most common reason for dementia in the aged population. AD increases the risk of seizures. Management of epilepsy in AD is difficult because of the possibility of drug interactions. Moreover, antiepileptic drug selection in the elderly needs special attention due to numerous pharmacokinetic factors. In the present study, the effect of lamotrigine (LTG) on the neuroprotective effect of memantine (MEM) was assessed. Materials and methodsA total of 32 adult male Wistar rats were divided into four groups: saline-treated group, aluminum chloride (AlCl3)-treated group, AlCl3+ MEM-treated group, and AlCl3+ MEM + LTG-treated group. AD was induced by intraperitoneal injection of AlCl3 (75 mg/kg/day) for 60 days, then the rats were evaluated using the Morris water maze, radial arm maze, novel object recognition, and passive avoidance tests. After accomplishing the behavioral tests, the rats were killed and their kidneys and brains were used for estimation of acetyl cholinesterase levels and histopathological studies. ResultsAlCl3 significantly impaired the performance in the Morris water maze, radial arm maze, novel object recognition test, and passive avoidance test and elevated acetyl cholinesterase levels in the cerebral cortex, hippocampus, serum, and kidneys. Moreover, the brain of AlCl3-treated rats showed an increased number of damaged neurons and glial cells. Concurrent administration of MEM and LTG significantly reversed behavioral and cognitive deficits induced by AlCl3. ConclusionLTG significantly potentiated the behavioral and cognitive improvement induced by MEM, a finding that suggests a neuroprotective profile of LTG and may hold promise in the management of dementia with epilepsy.