EFFECTS OF REPEATED ADMINISTRATION OF PROPENTOFYLLINE ON MEMORY IMPAIRMENT PRODUCED BY BASAL FOREBRAIN LESION IN RATS

The effects of repeated propentofylline administration on impairments of learning and memory in rats with basal forebrain lesions were inves tigated in several behavioral tasks (water maze, habituation and passi ve avoidance tasks). Rats were subjected to all the tasks in sequence. Basal forebrain lesions produced by bilateral injections of ibotenic acid (approximately 6 mug on each side) severely impaired performance in water maze, habituation and passive avoidance tasks. Repeated admin istration 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 whe n administration began one week after the basal forebrain lesions were produced. The impaired performance in habituation and passive avoidan ce tasks was also markedly ameliorated after repeated administration ( 24 and 26 days) of propentofylline. The rats with basal forebrain lesi ons exhibited a significant decrease in choline acetyltransferase acti vity in the cortex. Propentofylline significantly increased hippocampa l choline acetyltransferase activity in basal forebrain-lesioned rats compared with that in vehicle-treated basal forebrain-lesioned rats. H owever, cortical choline acetyltransferase activity in basal forebrain -lesioned animals was not affected by repeated propentofylline adminis tration. These results indicate that repeated administration of this a gent ameliorated the impaired performance of basal forebrain-lesioned rats in part by increasing hippocampal choline acetyltransferase activ ity. Propentofylline might be useful for the treatment of amensia and dementia.