Effects of memantine and donepezil on amyloid β-induced memory impairment in a delayed-matching to position task in rats

Kiyofumi Yamada, Masanori Takayanagi, Hiroyuki Kamei, Taku Nagai, Misato Dohniwa, Kana Kobayashi, Shigeru Yoshida, Tatsuo Ohhara, Kazuhiro Takauma, Toshitaka Nabeshima

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Abstract

We investigated the effects of memantine and donepezil on amyloid β (Aβ)-induced memory impairment in rats, which was assessed by a delayed-matching to position (DMPT) paradigm in three-lever operant chambers. Aggregated Aβ1-40 was microinjected bilaterally (1 nmol/side) into both CA1 and CA3 subfields of the hippocampus in rats that had previously performed the DMTP task. Memantine (20 mg/(kg day), s.c.) was continuously infused by an osmotic minipump for 4 weeks from 3 days before the microinjection of Aβ. Donepezil (2.5 mg/kg, p.o.) was administered 60 min before the DMTP test session. Bilateral microinjections of Aβ1-40 into the hippocampus resulted in a delayed, but persistent impairment of DMTP performance, which appeared more than 50 days after the injection. Memantine prevented the development of Aβ-induced memory impairment, while donepezil symptomatically alleviated the deficits. Because of a ceiling effect, the combination of donepezil with memantine failed to produce any additive or synergic effects. These results support the clinical data showing that memantine and donepezil are effective for the treatment of Alzheimer's disease. Moreover, it is suggested that memantine is effective for preventing Aβ-induced short-term memory impairment.

Original languageEnglish
Pages (from-to)191-199
Number of pages9
JournalBehavioural Brain Research
Volume162
Issue number2
DOIs
Publication statusPublished - 30-07-2005
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience

Cite this

Yamada, K., Takayanagi, M., Kamei, H., Nagai, T., Dohniwa, M., Kobayashi, K., Yoshida, S., Ohhara, T., Takauma, K., & Nabeshima, T. (2005). Effects of memantine and donepezil on amyloid β-induced memory impairment in a delayed-matching to position task in rats. Behavioural Brain Research, 162(2), 191-199. https://doi.org/10.1016/j.bbr.2005.02.036