Neuroprotective effects of citidine-5-diphosphocholine on impaired spatial memory in a rat model of cerebrovascular dementia

Citidine-5-diphosphocholine or citicoline (cdp-choline) is used as a neuroprotective and memory-enhancing drug in cerebral stroke,alzheimer's disease,and other neurovascular diseases. non-clinical studies have demonstrated the neuroprotective effects of cdp-choline in ischemic animal models. however,the relationship between the neuroprotective effect and the memory enhancing effect of cdp-choline is still unknown. no studies have demonstrated the ameliorative effect on impaired spatial memory and the suppressive effect on neuronal cell death of cdp-choline in the same model. in this study,we examined the effect of cdp-choline on impaired spatial memory and hippocampal ca1 neuronal death in rats subjected to repeated cerebral ischemia,and we compared the mechanism of cdp-choline to that of donepezil. seven days post administration of cdp-choline (100,300,1000 mg/kg per day,p.o.) or donepezil increased correct choices and reduced error choices in an eight-arm radial maze task in a dose-dependent manner. neuronal cell death of caspase-3 protein-positive neurons in the hippocampus were reduced by repeated administration of cdp-choline at the highest dose. these results suggest that cdp-choline has ameliorative effects on the impairment of spatial memory via hippocampal neuronal cell death in a rat model of cerebral ischemia. © the japanese pharmacological society.