Effects of metrifonate on impairment of learning and dysfunction of cholinergic neuronal system in basal forebrain-lesioned rats

Akio Itoh, Atsumi Nitta, Mitsuhiko Hirose, Takaaki Hasegawa, Toshitaka Nabeshima

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Several studies have indicated the possibility of using cholinesterase (ChE) inhibitors as therapeutic drugs for Alzheimer's disease. Metrifonate (MTF) is an organophosphorus compound that has been used in the treatment of schistosomiasis. In this study, we investigated the effects of MTF on the impairment of learning and memory, decreased ChE activity and extracellular acetylcholine (ACh) levels in basal forebrain (BF)-lesioned rats. The oral administration of MTF improved the BF-lesion-induced impairment of performance on passive avoidance task. Further, MTF reduced ChE activity in the cerebral cortex. In vivo brain microdialysis studies showed that MTF significantly increased the release of ACh, but decreased that of choline (Ch) in the cerebral cortex of BF-lesioned rats. These results indicated that MTF ameliorates the impairment of performance on passive avoidance task in BF-lesioned rats by increasing the extracellular ACh levels by inhibiting ChE. This suggested that MTF may be useful as a therapeutic drug for Alzheimer's disease.

Original languageEnglish
Pages (from-to)165-167
Number of pages3
JournalBehavioural Brain Research
Issue number1-2
Publication statusPublished - 02-1997
Externally publishedYes


All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience

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