EFFECTS OF MCI-225 ON MEMORY AND GLUCOSE-UTILIZATION IN BASAL FOREBRAIN-LESIONED RATS

The effects of MCI-225 on amnesia, the cerebral glucose metabolism, an d choline acetyltransferase (ChAT) activity in basal forebrain (BF)-le sioned rats were studied in comparison with those of tacrine. Bilatera l BF lesions with ibotenic acid impaired the performance in passive av oidance (PA) tasks. Single administration of MCI-225 (10 mg/kg, PO) af ter a 2-week postoperative recovery period, increased the escape laten cies in the PA task, but was not statistically significant. Repeated a dministration of MCI-225 (0.3 and 1 mg/kg, PO for 6 days) significantl y reversed the PA failure. The BF-lesioned rat exhibited a marked decr ease in the local cerebral glucose utilization (LCGU) in the frontal c ortex, parietal cortex, and caudate-putamen. MCI-225 (1 mg/kg, PO for 5 days) significantly ameliorated the reduction of the LCGU in the par ietal cortex. MCI-225 did not change the decrease in the cortical ChAT activity induced by the BF lesion. Repeated administration of tacrine reversed the PA failure (0.3 mg/kg, PO) but failed to prevent the dec rement in the LCGU and the ChAT activity. These results suggest that M CI-225 could be effective in the treatment of senile dementia of the A lzheimer type, which is accompanied with both deficit in the BF-cortex cholinergic neuron and cerebral glucose hypometabolism.