Synergistic effects of selegiline and donepezil on cognitive impairment induced by amyloid beta (25-35)

Hiroko Tsunekawa, Yukihiro Noda, Akihiro Mouri, Fumio Yoneda, Toshitaka Nabeshima

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)


Selegiline, an irreversible inhibitor of monoamine oxidase B used in the treatment of Parkinson's disease, has been demonstrated to have a potential cognition-improving effect in patients with Alzheimer's disease (AD) undergoing treatment with an acetylcholinesterase inhibitor donepezil. To confirm such clinical events, we investigated whether co-administration of donepezil with selegiline had a synergistic cognition-improving effect in an animal model of AD. Intracerebroventricular injection of amyloid beta protein fragment 25-35 [Aβ(25-35)] induced impairment of learning and memory in a Y-maze, novel object recognition and contextual fear conditioning tests. Either donepezil or selegiline alone improved the cognitive impairments in the Y-maze and conditioned fear learning tasks in Aβ(25-35)-injected mice, whereas donepezil, but not selegiline, failed to improve the impairment in a novel object recognition task. Co-administration of donepezil with selegiline, at doses that do not exert efficacy individually, significantly improved the deficits in all three tests, indicating a synergistic cognition-improving effect. These alleviating effects were antagonized by pretreatment with a muscarinic receptor antagonist scopolamine and a dopamine receptor antagonist haloperidol. These results suggest that selegiline potentiates the effect of donepezil on the cognitive impairment, and that the synergistic effect may be mediated through both the cholinergic and dopaminergic systems.

Original languageEnglish
Pages (from-to)224-232
Number of pages9
JournalBehavioural Brain Research
Issue number2
Publication statusPublished - 19-07-2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience


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