Improvement by nefiracetam of /?-amyloid-(l-42)-induced learning and memory impairments in rats

Kiyofumi Yamada, Tomoko Tanaka, Takayoshi Mamiya, Tadashi Shiotani, Tsutomu Kameyama, Toshitaka Nabeshima

Research output: Contribution to journalArticle

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Abstract

1 We have previously demonstrated that continuous i.c.v. infusion of amyloid /?-peptide (A/5), the major constituent of senile plaques in the brains of patients with Alzheimer1 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-oxol-pyrrolidinyl) acetamide, DM-9384] on A/?-(l-42)-induced learning and memory deficits in rats. 3 In the A/?-(l-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-l)-infused control rats. 4 Nefiracetam, at a dose range of 1-10 mg kg1, improved learning and memory deficits in the A/?-(l-42)-infused rats when it was administered p.o. l h before the behavioural tests. 5 Nefiracetam at a dose of 3 mg kg1 p.o. increased the activity of choline acetyltransferase in the hippocampus of A/?-(l-42)-infused rats. 6 Nefiracetam increased dopamine turnover in the cerebral cortex and striatum of A/?-(l-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 Alzheimer1 s disease.

Original languageEnglish
Pages (from-to)235-244
Number of pages10
JournalBritish Journal of Pharmacology
Volume126
Issue number1
DOIs
Publication statusPublished - 01-01-1999
Externally publishedYes

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Amyloid
Learning
Memory Disorders
Avoidance Learning
Hydroxyindoleacetic Acid
Choline O-Acetyltransferase
Amyloid Plaques
nefiracetam
Short-Term Memory
Cerebral Cortex
Hippocampus
Dopamine
Serotonin
Norepinephrine
Water
Brain

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Yamada, Kiyofumi ; Tanaka, Tomoko ; Mamiya, Takayoshi ; Shiotani, Tadashi ; Kameyama, Tsutomu ; Nabeshima, Toshitaka. / Improvement by nefiracetam of /?-amyloid-(l-42)-induced learning and memory impairments in rats. In: British Journal of Pharmacology. 1999 ; Vol. 126, No. 1. pp. 235-244.
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Improvement by nefiracetam of /?-amyloid-(l-42)-induced learning and memory impairments in rats. / Yamada, Kiyofumi; Tanaka, Tomoko; Mamiya, Takayoshi; Shiotani, Tadashi; Kameyama, Tsutomu; Nabeshima, Toshitaka.

In: British Journal of Pharmacology, Vol. 126, No. 1, 01.01.1999, p. 235-244.

Research output: Contribution to journalArticle

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