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

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.