Metrifonate treatment enhances acquisition of eyeblink conditioning in aging rabbits

Pharmacology, Biochemistry, and Behavior
M A Kronforst-CollinsJ F Disterhoft

Abstract

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.

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Citations

May 28, 2004·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·Pascale C BougerFranz-Josef van der Staay
Mar 12, 1997·European Journal of Pharmacology·M RiekkinenP Riekkinen
Feb 10, 1998·European Journal of Pharmacology·M RiekkinenP Riekkinen
Jan 7, 1999·European Journal of Pharmacology·F Poindessous-JazatM H Bassant
Feb 18, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Wendy W WuJames Maylie
Jan 1, 2010·Future Neurology·M Matthew Oh, John F Disterhoft
Jun 21, 2014·Pharmacological Reports : PR·Tina Mele, Damijana Mojca Jurič
Feb 7, 2006·Journal of Physiology, Paris·John F Disterhoft, M Matthew Oh
Mar 23, 2005·Brain Research·Toshiro SakamotoMasayoshi Mishina
Sep 1, 2006·Trends in Neurosciences·John F Disterhoft, M Matthew Oh
Apr 20, 2019·Expert Review of Neurotherapeutics·Alexandre A de CastroTeodorico C Ramalho
Feb 15, 2011·Behavioural Brain Research·Lianne RobinsonGernot Riedel

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