The effects of repeated propentofylline administration on impairments of learning and memory in rats with basal forebrain lesions were investigated in several behavioral tasks (water maze, habituation and passive avoidance tasks). Rats were subjected to all the tasks in sequence. Basal forebrain lesions produced by bilateral injections of ibotenic acid (approximately 6 μg on each side) severely impaired performance in water maze, habituation and passive avoidance tasks. Repeated administration of propentofylline (10 and 25 mg/kg per day for 14 days, p.o.) improved the deficits of performance in a water maze task, even when administration began one week after the basal forebrain lesions were produced. The impaired performance in habituation and passive avoidance tasks was also markedly ameliorated after repeated administration (24 and 26 days) of propentofylline. The rats with basal forebrain lesions exhibited a significant decrease in choline acetyltransferase activity in the cortex. Propentofylline significantly increased hippocampal choline acetyltransferase activity in basal forebrain-lesioned rats compared with that in vehicle-treated basal forebrain-lesioned rats. However, cortical choline acetyltransferase activity in basal forebrain-lesioned animals was not affected by repeated propentofylline administration. These results indicate that repeated administration of this agent ameliorated the impaired performance of basal forebrain-lesioned rats in part by increasing hippocampal choline acetyltransferase activity. Propentofylline might be useful for the treatment of amensia and dementia.
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