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

Behavioural Brain Research
Hiroko TsunekawaToshitaka Nabeshima

Abstract

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 [Abeta(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 Abeta(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 scopolamin...Continue Reading

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