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

Pharmacol Biochem Behav. 1995 Aug;51(4):935-9. doi: 10.1016/0091-3057(95)00087-d.

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Avoidance Learning / drug effects
  • Brain Chemistry / drug effects
  • Choline O-Acetyltransferase / metabolism
  • Glucose / metabolism*
  • Hippocampus / drug effects
  • Hippocampus / enzymology
  • Hippocampus / metabolism
  • Male
  • Memory / drug effects*
  • Parietal Lobe / drug effects
  • Parietal Lobe / enzymology
  • Parietal Lobe / metabolism
  • Piperazines / pharmacology*
  • Prosencephalon / physiology*
  • Psychotropic Drugs / pharmacology*
  • Pyrimidines / pharmacology*
  • Rats
  • Rats, Wistar
  • Tacrine / pharmacology

Substances

  • Piperazines
  • Psychotropic Drugs
  • Pyrimidines
  • MCI 225
  • Tacrine
  • Choline O-Acetyltransferase
  • Glucose