Abstract
1215
Objectives Positron emission tomography using [18F]fluoro-2-deoxyglucose (FDG-PET) is a useful tool for measuring cerebral glucose metabolism (CMRglc), which is an index of neuronal activity. Donepezil, an acetylcholine esterase inhibitor (AChEI), has been used as a standard treatment for Alzheimer’s disease (AD). The aim of present study was to characterize the effects of donepezil on CMRglc using FDG-PET in rhesus monkeys.
Methods We investigated the effects of donepezil 500 µg/kg, scopolamine, a non-selective muscarinic ACh receptor (mAChR) antagonist, 30 µg/kg, and the effect of coadministration of both drugs on CMRglc in three male rhesus monkeys (5 - 6 y). Drugs were intramuscularly administered 45 min prior to PET measurements. PET scans were performed using a high-resolution animal PET scanner (SHR-7700; Hamamatsu Photonics K.K., Hamamatsu, Japan). Sixty minutes of emission data consist of 22 dynamic frames were collected following an intravenous injection of FDG (~ 370 MBq).
Results Donepezil increased CMRglc in all regions of interest (ROIs), and mAChR blockade by scopolamine also increased the CMRglc in all ROIs, while coadministration of donepezil and scopolamine showed no increased CMRglc.
Conclusions The present results demonstrated that administration of donepezil or scopolamine alone increased the CMRglc in rhesus monkeys, however donepezil-induced increase was abolished by simultaneous administration of scopolamine. This suggests that mAChR function plays an important role in the effect of donepezil on CMRglc.
- © 2009 by Society of Nuclear Medicine