Journal
BEHAVIOURAL BRAIN RESEARCH
Volume 190, Issue 2, Pages 224-232Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbr.2008.03.002
Keywords
Alzheimer's disease (AD); amyloid beta (25-35) [A beta((25-35))]; cognitive impairment; cholinergic systems; donepezil dopaminergic systems; selegiline
Categories
Ask authors/readers for more resources
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 [A beta((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 A beta((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. (C) 2008 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available