J. Eguchi et al., EFFECTS OF MCI-225 ON MEMORY AND GLUCOSE-UTILIZATION IN BASAL FOREBRAIN-LESIONED RATS, Pharmacology, biochemistry and behavior, 51(4), 1995, pp. 935-939
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.