Vol. 281, Issue 3, 1408-1414, 1997

Functional Activation of Cerebral Blood Flow Abolished by Scopolamine Is Reversed by Cognitive Enhancers Associated with Cholinesterase Inhibition: A Positron Emission Tomography Study in Unanesthetized Monkeys

Hideo Tsukada , Takeharu Kakiuchi, Ichiro Ando and Yasuomi Ouchi

Central Research Laboratory, Hamamatsu Photonics K.K., Shizuoka, Japan (H.T., T.K., I.A.), Subfemtomole Biorecognition Project, Japan Science and Technology Corporation, Osaka, Japan (H.T.), and Positron Medical Center, Hamamatsu Medical Center, Shizuoka, Japan (Y.O.)

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, using ¹⁵O-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.