Abstract |
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.
|
Authors | J Eguchi, K Iwai, T Yuasa, M Egawa, T Komatsu, K Saito |
Journal | Pharmacology, biochemistry, and behavior
(Pharmacol Biochem Behav)
Vol. 51
Issue 4
Pg. 935-9
(Aug 1995)
ISSN: 0091-3057 [Print] United States |
PMID | 7675880
(Publication Type: Comparative Study, Journal Article)
|
Chemical References |
- Piperazines
- Psychotropic Drugs
- Pyrimidines
- MCI 225
- Tacrine
- Choline O-Acetyltransferase
- Glucose
|
Topics |
- Animals
- Avoidance Learning
(drug effects)
- Brain Chemistry
(drug effects)
- Choline O-Acetyltransferase
(metabolism)
- Glucose
(metabolism)
- Hippocampus
(drug effects, enzymology, metabolism)
- Male
- Memory
(drug effects)
- Parietal Lobe
(drug effects, enzymology, metabolism)
- Piperazines
(pharmacology)
- Prosencephalon
(physiology)
- Psychotropic Drugs
(pharmacology)
- Pyrimidines
(pharmacology)
- Rats
- Rats, Wistar
- Tacrine
(pharmacology)
|