MKC-231, a choline uptake enhancer, ameliorates working memory deficits and decreased hippocampal acetylcholine induced by ethylcholine aziridinium ion in mice

J Neural Transm Gen Sect. 1994;98(1):1-13. doi: 10.1007/BF01277590.


The effects of acute and chronic administration of MKC-231, a new choline uptake enhancer, and two other nootropic agents, linopiridine (Dup 996) and tetrahydroaminoacridine (THA) on working memory deficits and decreased hippocampal acetylcholine (ACh) content were studied in a delayed non-matching to sample task, using a T-maze, in ethylcholine aziridinium ion (AF64A)-treated mice. Treatment with AF64A (3.5 nmol, i.c.v.) produced memory deficits and decreased hippocampal ACh content. In acute behavioral experiments, MKC-231 and THA had no significant effect on AF64A-induced memory deficits at any doses tested (0.3, 1.0 and 3.0 mg/kg), whereas Dup 996, at a dose of 1.0 mg/kg, significantly improved memory deficits. In chronic experiments, MKC-231 improved memory deficit at all doses tested (0.3, 1.0, or 3.0 mg/kg p.o., once daily for 11 days) and Dup 996 did so only at a dose of 3.0 mg/kg, whereas THA did not improve memory deficit at any doses tested. In acute neurochemical experiments, MKC-231 and THA did not reverse the AF64A-induced hippocampal ACh depletion. Dup 996, however, further decreased hippocampal ACh content compared to that in the AF64A-treated group. In chronic experiments, MKC-231 significantly reversed hippocampal ACh depletion at doses of 0.3 and 1.0 mg/kg, whereas neither Dup 996 nor THA reversed hippocampal ACh depletion at any doses tested. These results indicate that MKC-231 improved the AF64A-induced working memory deficit and hippocampal ACh depletion, probably by recovering reduced high-affinity choline uptake and ACh release.

MeSH terms

  • Acetylcholine / metabolism*
  • Acetylcholinesterase / metabolism
  • Amnesia
  • Animals
  • Aziridines
  • Choline / analogs & derivatives
  • Choline Deficiency
  • Data Interpretation, Statistical
  • Habituation, Psychophysiologic / drug effects
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Indoles / pharmacology
  • Injections, Intraventricular
  • Male
  • Maze Learning
  • Memory / drug effects*
  • Memory Disorders / chemically induced
  • Mice
  • Mice, Inbred Strains
  • Pyridines / pharmacology
  • Quinolines / administration & dosage*
  • Synaptic Transmission*
  • Tacrine / pharmacology


  • Aziridines
  • Indoles
  • Pyridines
  • Quinolines
  • Tacrine
  • ethylcholine aziridinium
  • Acetylcholinesterase
  • linopirdine
  • Choline
  • Acetylcholine
  • MKC 231