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

研究成果: Article

52 引用 (Scopus)

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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.

元の言語English
ページ(範囲)224-232
ページ数9
ジャーナルBehavioural Brain Research
190
発行部数2
DOI
出版物ステータスPublished - 19-07-2008
外部発表Yes

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All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience

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