TY - JOUR T1 - 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 JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1408 LP - 1414 VL - 281 IS - 3 AU - Hideo Tsukada AU - Takeharu Kakiuchi AU - Ichiro Ando AU - Yasuomi Ouchi Y1 - 1997/06/01 UR - http://jpet.aspetjournals.org/content/281/3/1408.abstract N2 - 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. The American Society for Pharmacology and Experimental Therapeutics ER -