TY - JOUR
T1 - Donepezil-induced improvement in delayed matching accuracy by young and old rhesus monkeys
AU - Buccafusco, Jerry J.
AU - Terry, Alvin V.
N1 - Funding Information:
The authors would like to thank primate technicians Nancy Kille and Ritu Duhan for their skillful contributions. We would also like to thank Dr. Michael W. Decker of Abbott Labs for suggesting this study and for his supportive comments and suggestions. This work was supported in part by the Institute for the Study of Aging, Abbott Labs, and the Office of Research and Development, Medical Research Service, Department of Veterans Affairs.
PY - 2004/8
Y1 - 2004/8
N2 - Donepezil (Aricept®), a long-acting cholinesterase inhibitor, is widely used in the treatment of Alzheimer's disease to improve cognition and memory. Many drugs within the class of cognition-enhancing agents, both currently approved medications and those under development, have clinical indications narrowly relegated to Alzheimer's disease. The purpose of this study was to determine whether the efficacy attributed to donepezil in its ability to improve delayed matching accuracy by monkeys was independent of age. Male and female rhesus monkeys (n = 17) ranging from 9 to 29 yr of age were administered donepezil (10, 25, 50, and 100 μg/kg, im) during 4 discrete test days. Donepezil treatment improved average task accuracy, but intersubject variability prohibited statistical significance. When animals were considered individually, the most effective dose of donepezil was associated with a highly significant increase in group task performance that was consistent with enhanced recall during testing. The variability associated with the dose-response analysis was attributable primarily to subject age, such that older monkeys required higher doses of donepezil. Yet at doses that were effective in all subjects, there was no relationship between age and the improvement in task accuracy. Likewise, there was no association between baseline task proficiency and improvement in task accuracy.
AB - Donepezil (Aricept®), a long-acting cholinesterase inhibitor, is widely used in the treatment of Alzheimer's disease to improve cognition and memory. Many drugs within the class of cognition-enhancing agents, both currently approved medications and those under development, have clinical indications narrowly relegated to Alzheimer's disease. The purpose of this study was to determine whether the efficacy attributed to donepezil in its ability to improve delayed matching accuracy by monkeys was independent of age. Male and female rhesus monkeys (n = 17) ranging from 9 to 29 yr of age were administered donepezil (10, 25, 50, and 100 μg/kg, im) during 4 discrete test days. Donepezil treatment improved average task accuracy, but intersubject variability prohibited statistical significance. When animals were considered individually, the most effective dose of donepezil was associated with a highly significant increase in group task performance that was consistent with enhanced recall during testing. The variability associated with the dose-response analysis was attributable primarily to subject age, such that older monkeys required higher doses of donepezil. Yet at doses that were effective in all subjects, there was no relationship between age and the improvement in task accuracy. Likewise, there was no association between baseline task proficiency and improvement in task accuracy.
KW - Aging
KW - Cholinesterase inhibitor
KW - Cognition
KW - Delayed matching
KW - Donepezil
KW - Memory
KW - Nonhuman primate
KW - Recall
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U2 - 10.1385/jmn:24:1:085
DO - 10.1385/jmn:24:1:085
M3 - Article
C2 - 15314255
AN - SCOPUS:16544394141
VL - 24
SP - 85
EP - 91
JO - Molecular and Chemical Neuropathology
JF - Molecular and Chemical Neuropathology
SN - 0895-8696
IS - 1
ER -