Metrifonate treatment enhances acquisition of eyeblink conditioning in aging rabbits

M. A. Kronforst-Collins, P. L. Moriearty, M. Ralph, R. E. Becker, B. Schimdt, L. T. Thompson, J. F. Disterhoft*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


The cholinergic system is known to show deterioration during aging and Alzheimer's disease. In response, a therapeutic approach to Alzheimer's disease has been to attempt to compensate for the decrease in central cholinergic function by potentiating the activity of the remaining intact cholinergic cells with cholinesterase inhibitors. In this study treatment with the long-lasting cholinesterase inhibitor metrifonate enhanced acquisition of eyeblink conditioning in aging rabbits without producing interfering side effects. The effects of metrifonate on central and peripheral cholinesterase activity were evaluated, as was the involvement of plasma atropine esterase activity on the central and peripheral response to metrifonate. Results demonstrate that metrifonate can produce predictable, dose-dependent ChE inhibition. Associative learning in the aging rabbit was improved by metrifonate-induced steady state ChE inhibition within a range of 30-80%. Metrifonate was behaviorally effective in the absence of the severe side effects which typically plague cholinesterase inhibitors, suggesting that metrifonate is a possible treatment for the cognitive deficits resulting from normal aging and Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)103-110
Number of pages8
JournalPharmacology Biochemistry and Behavior
Issue number1
StatePublished - Jan 1996


  • aging
  • cholinesterase
  • cholinesterase inhibitor
  • dichlorvos
  • eyeblink conditioning
  • learning
  • metrifonate
  • rabbits

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience


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