TY - JOUR
T1 - Effects of metrifonate on impairment of learning and dysfunction of cholinergic neuronal system in basal forebrain-lesioned rats
AU - Itoh, Akio
AU - Nitta, Atsumi
AU - Hirose, Mitsuhiko
AU - Hasegawa, Takaaki
AU - Nabeshima, Toshitaka
N1 - Funding Information:
This work was partly supported by an SRF Grant for Biomedical Research, by Grants-in-Aid for Scientific Research from Ministry of Education, Science, and Culture of Japan (07557009), a grant for Gerontological Science Research from the Ministry of Health and Welfare of Japan (91A-2406) and a grant from the Uehara Memorial Foundation.
PY - 1997/2
Y1 - 1997/2
N2 - 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.
AB - 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.
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U2 - 10.1016/S0166-4328(97)86062-7
DO - 10.1016/S0166-4328(97)86062-7
M3 - Article
C2 - 9062677
AN - SCOPUS:19244372524
SN - 0166-4328
VL - 83
SP - 165
EP - 167
JO - Behavioural Brain Research
JF - Behavioural Brain Research
IS - 1-2
ER -
