EFFECTS OF METRIFONATE ON MEMORY IMPAIRMENT AND CHOLINERGIC DYSFUNCTION IN RATS

Metrifonate is an organophosphorous compound that has been used in the treatment of schistosomiasis. In this study, we investigated the effe cts of metrifonate on the impairment of learning and on central cholin ergic dysfunction in scopolamine-treated and basal forebrain-lesioned rats. Oral administration of metrifonate (5.0-15.0 mg/kg) ameliorated the scopolamine- and basal forebrain lesion-induced learning impairmen t in the water maze and passive avoidance tasks. Metrifonate (50 and 1 00 mg/kg) also significantly increased extracellular acetylcholine lev els but decreased choline levels in the cerebral cortex of the basal f orebrain-lesioned rats. The basal forebrain lesion decreased the choli nesterase activity in the cerebral cortex, and metrifonate (100 mg/kg) further reduced the cholinesterase activity. However, cholinesterase inhibition was not observed at the dose that ameliorated learning impa irments. These results indicated that metrifonate ameliorated the impa irment of learning in both scopolamine-treated and basal forebrain-les ioned rats by not only increasing extracellular acetylcholine levels b y inhibiting cholinesterase, but also by undefined other mechanism(s). This finding suggests the usefulness of metrifonate for the therapy o f Alzheimer's disease.