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

Kotaro Takasaki, Kanako Uchida, Risako Fujikawa, Ai Nogami, Kazuya Nakamura, Chihiro Kawasaki, Kazuko Yamaguchi, Masahiko Morita, Koji Morishita, Kaori Kubota, Shutaro Katsurabayashi, Kenichi Mishima, Michihiro Fujiwara, Katsunori Iwasaki

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26 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)232-237
Number of pages6
JournalJournal of Pharmacological Sciences
Issue number2
Publication statusPublished - 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology


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