TY - JOUR
T1 - Effects of memantine and donepezil on amyloid β-induced memory impairment in a delayed-matching to position task in rats
AU - Yamada, Kiyofumi
AU - Takayanagi, Masanori
AU - Kamei, Hiroyuki
AU - Nagai, Taku
AU - Dohniwa, Misato
AU - Kobayashi, Kana
AU - Yoshida, Shigeru
AU - Ohhara, Tatsuo
AU - Takauma, Kazuhiro
AU - Nabeshima, Toshitaka
N1 - Funding Information:
We would like to thank Drs. Wojciech Danysz and Yoshiharu Yamanishi for critical reading of the manuscript. We also thank Merz Pharmaceuticals and Eisai Co. Ltd. for providing us with memantine and donepezil, respectively. This study was supported in part by Grant-in-aid for Scientific Research 14370031 from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by a Grant from the Smoking Research Foundation.
PY - 2005/7/30
Y1 - 2005/7/30
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbr.2005.02.036
DO - 10.1016/j.bbr.2005.02.036
M3 - Article
C2 - 15904984
AN - SCOPUS:20444481258
SN - 0166-4328
VL - 162
SP - 191
EP - 199
JO - Behavioural Brain Research
JF - Behavioural Brain Research
IS - 2
ER -