Abstract
The effects of somatosensory stimulation on the regional cerebral blood flow (rCBF) response were studied in unanesthetized monkeys before and after treatment with scopolamine and three cognitive enhancers (physostigmine, E2020 and tacrine) that inhibit cholinesterase, using15O-labeled water and high-resolution positron emission tomography. Under control conditions, somatosensory stimulation induced a significant increase in the rCBF response in the contralateral somatosensory cortex of monkey brain. Intravenous administration of scopolamine (50 μg/kg) resulted in abolishment of the rCBF response to stimulation. The rCBF response abolished by pretreatment with scopolamine was recovered by administration of physostigmine (1 or 10 μg/kg), E2020 (10 or 100 μg/kg) or tacrine (100 or 1000 μg/kg), in a dose-dependent manner. The effect of E2020 (100 μg/kg) on the rCBF response lasted for >4 hr, whereas the effects of physostigmine and tacrine were of shorter duration. These findings suggest that these compounds reversed the scopolamine-abolished rCBF response to somatosensory stimulation via enhancement of cholinergic neurotransmission, which was mainly induced by cholinesterase inhibition.
Footnotes
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Send reprint requests to: Hideo Tsukada, Ph.D., Central Research Laboratory, Hamamatsu Photonics K.K., 5000 Hirakuchi, Hamakita, Shizuoka 434, Japan.
- Abbreviations:
- AChE
- acetylcholinesterase
- AD
- Alzheimer’s disease
- BuChE
- butyrylcholinesterase
- E2020
- 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride
- PET
- positron emission tomography
- rCBF
- regional cerebral blood flow
- rCMR
- regional cerebral metabolic rate
- ROI
- region(s) of interest
- Received September 23, 1996.
- Accepted January 29, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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