title: Effects of memantine and donepezil on amyloid beta-induced memory impairment in a delayed-matching to position task in rats.
abstract: We investigated the effects of memantine and donepezil on amyloid beta (Abeta)-induced memory impairment in rats, which was assessed by a delayed-matching to position (DMPT) paradigm in three-lever operant chambers. Aggregated Abeta1-40 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 Abeta. Donepezil (2.5 mg/kg, p.o.) was administered 60 min before the DMTP test session. Bilateral microinjections of Abeta1-40 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 Abeta-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 Abeta-induced short-term memory impairment.
authors.affiliation: Laboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada
authors.forename: Masanori
authors.initials: M
authors.lastname: Takayanagi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kamei
authors.forename: Taku
authors.initials: T
authors.lastname: Nagai
authors.forename: Misato
authors.initials: M
authors.lastname: Dohniwa
authors.forename: Kana
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yoshida
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Ohhara
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takuma
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nabeshima
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D000077265:Donepezil; D004333:Drug Administration Routes; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage*; D005508:Food Deprivation; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007189:Indans / Q000008:administration & dosage*; D008297:Male; D008559:Memantine / Q000008:administration & dosage*; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D010446:Peptide Fragments / Q000633:toxicity*; D010880:Piperidines / Q000008:administration & dosage*; D051381:Rats; D011916:Rats, Inbred F344; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D007189:Indans; D010446:Peptide Fragments; D010880:Piperidines; C078592:amyloid beta-protein (1-40); D000077265:Donepezil; D008559:Memantine