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Effects of MCI-225 on memory and glucose utilization in basal forebrain-lesioned rats.

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.
AuthorsJ Eguchi, K Iwai, T Yuasa, M Egawa, T Komatsu, K Saito
JournalPharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 51 Issue 4 Pg. 935-9 (Aug 1995) ISSN: 0091-3057 [Print] United States
PMID7675880 (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)

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