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, and choline acetyltransferase (ChAT) activity in basal forebrain (BF)-lesioned rats were studied in comparison with those of tacrine. Bilateral BF lesions with ibotenic acid impaired the performance in passive avoidance (PA) tasks. Single administration of MCI-225 (10 mg/kg, PO) after a 2-week postoperative recovery period, increased the escape latencies in the PA task, but was not statistically significant. Repeated administration of MCI-225 (0.3 and 1 mg/kg, PO for 6 days) significantly reversed the PA failure. The BF-lesioned rat exhibited a marked decrease in the local cerebral glucose utilization (LCGU) in the frontal cortex, parietal cortex, and caudate-putamen. MCI-225 (1 mg/kg, PO for 5 days) significantly ameliorated the reduction of the LCGU in the parietal 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 decrement in the LCGU and the ChAT activity. These results suggest that MCI-225 could be effective in the treatment of senile dementia of the Alzheimer type, which is accompanied with both deficit in the BF-cortex cholinergic neuron and cerebral glucose hypometabolism.
Eguchi
J
J
Pharmaceuticals Laboratory I, Yokohama Research Center, Mitsubishi Chemical Corporation, Japan.
Iwai
K
K
Yuasa
T
T
Egawa
M
M
Komatsu
T
T
Saito
K
K
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects*; D010296:Parietal Lobe / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D016548:Prosencephalon / Q000502:physiology*; D011619:Psychotropic Drugs / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013619:Tacrine / Q000494:pharmacology
D010879:Piperazines; D011619:Psychotropic Drugs; D011743:Pyrimidines; C085298:MCI 225; D013619:Tacrine; D002795:Choline O-Acetyltransferase; D005947:Glucose