Melatonin and Vitamin C modulate cholinergic neurotransmission and oxidative stress in scopolamine-induced rat model of memory impairment

Abstract

Background: Cognitive dysfunction which characterizes dementia is reportedly caused by multiple factors including oxidant-antioxidant imbalance, inflammation, alteration in synaptic neurotransmission. Despite the arrays of drugs available in managing dementia, it appears no single drug can effectively treat dementia. Since it is multifactorial, combining potential drugs may provide neuroprotective impact. As such, this study investigated the neuroprotective effects of melatonin and vitamin C on scopolamine model of cognitive impairment in rats and the possible mechanism of action.

Methods: Thirty male Wistar rats were divided to receive either normal saline (5 ml/kg, p.o), scopolamine (1 mg/kg, i.p.), donepezil (2 mg/kg, p.o), melatonin (10 mg/kg, p.o), vitamin C (100 mg/kg. p.o) or melatonin plus vitamin C. Cognitive impairment was induced by daily injection of scopolamine (1 mg/kg, i.p.), after which different treatment regimen were administered for 15 days. Spatial memory was assessed using Morris Water Maze and modified light and dark box. The brain was processed for malondialdehyde (MDA), reduced glutathione (GSH) and acetylcholinesterase (AchE) activity.

Results: Scopolamine-treated rats with no intervention showed impaired learning and memory as depicted by a significant (p<0.05) increase in escape latency, reduction in the frequency of visit to the escape aperture, increased MDA, decreased GSH and elevated acetylcholinesterase activity when compared to other groups. Interventions with melatonin or/and vitamin C reversed these responses respectively. The melatonin plus vitamin C treated group compared favorably with donepezil (reference group).

Conclusion: Melatonin and vitamin C show neuroprotective effect in attenuating cognitive impairment in scopolamine-induced model by modulating oxidative stress pathway and enhancing cholinergic neurotransmission.

Keywords: Dementia, Melatonin, Vitamin C, Memory, Scopolamine.