METRIFONATE TREATMENT ENHANCES ACQUISITION OF EYEBLINK CONDITIONING IN AGING RABBITS

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 centr al 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 cen tral and peripheral cholinesterase activity were evaluated, as was the involvement of plasma atropine esterase activity on the central and p eripheral response to metrifonate. Results demonstrate that metrifonat e can produce predictable, dose-dependent ChE inhibition. Associative learning in the aging rabbit was improved by metrifonate-induced stead y state ChE inhibition within a range of 30-80%. Metrifonate was behav iorally effective in the absence of the severe side effects which typi cally plague cholinesterase inhibitors, suggesting that metrifonate is a possible treatment for the cognitive deficits resulting from normal aging and Alzheimer's disease. Copyright (C) 1997 Elsevier Science In c.