January 1999, Volume 126, Issue 1, Pages 235 - 244

Original Article

Improvement by nefiracetam of -amyloid-(1-42)-induced learning and memory impairments in rats Kiyofumi Yamada1, Tomoko Tanaka1,2, Takayoshi Mamiya1, Tadashi Shiotani1, Tsutomu Kameyama2 & Toshitaka Nabeshima1,3 1Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Showa-ku, Nagoya 466-8560, Japan     2Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Tenpaku-ku, Nagoya 468-0077, Japan     3Author for correspondence: E-mail: tnabeshi@tsuru.med.nagoya-u.ac.jp

Keywords

Alzheimer's disease;   amyloid -peptide;   nefiracetam (DM-9384);   reference memory;   voltage-sensitive calcium channels;   working memory

Abstract

1   We have previously demonstrated that continuous i.c.v. infusion of amyloid -peptide (A), the major constituent of senile plaques in the brains of patients with Alzheimer's disease, results in learning and memory deficits in rats. 2   In the present study, we investigated the effects of nefiracetam [N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide, DM-9384] on A-(1-42)-induced learning and memory deficits in rats. 3   In the A-(1-42)-infused rats, spontaneous alternation behaviour in a Y-maze task, spatial reference and working memory in a water maze task, and retention of passive avoidance learning were significantly impaired as compared with A-(40-1)-infused control rats. 4   Nefiracetam, at a dose range of 1 - 10 mg kg-1, improved learning and memory deficits in the A-(1-42)-infused rats when it was administered p.o. 1 h before the behavioural tests. 5   Nefiracetam at a dose of 3 mg kg-1 p.o. increased the activity of choline acetyltransferase in the hippocampus of A-(1-42)-infused rats. 6   Nefiracetam increased dopamine turnover in the cerebral cortex and striatum of A-(1-42)-infused rats, but failed to affect the noradrenaline, serotonin and 5-hydroxyindoleacetic acid content. 7   These results suggest that nefiracetam may be useful for the treatment of patients with Alzheimer's disease.

Received 22 June 1998; Revised 5 October 1998; Accepted 20 October 1998

^© Macmillan Publishers Ltd 1999