Cognitive and regional cerebral blood flow consequences of cholinergic antagonism in healthy human adults.
Item
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Title
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Cognitive and regional cerebral blood flow consequences of cholinergic antagonism in healthy human adults.
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Identifier
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AAI8914793
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identifier
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8914793
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Creator
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Smith, Gwenn Susan.
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Contributor
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Adviser: Richard J. Bodnar
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Date
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1988
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Language
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English
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Publisher
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City University of New York.
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Subject
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Psychology, Psychobiology | Biology, Neuroscience
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Abstract
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The interrelation of neurochemical function, cerebral metabolism and behavior has been largely unexplored in the human. The purpose of this investigation was to elucidate such interactions within the cholinergic system, a system implicated in the cognitive deficits of such neurodegenerative disorders as Alzheimer's disease. Neurochemical manipulation was performed by administration of scopolamine, a muscarinic cholinergic receptor antagonist. The effects of cholinergic receptor blockade on cerebral perfusion were assessed by measurements of regional cerebral blood flow (rCBF), using the {dollar}\sp{lcub}133{rcub}{dollar}Xenon inhalation technique, with 16 detectors over each cerebral hemisphere. Neuropsychological assessment was conducted to evaluate scopolamine's effects on attention and memory.;To establish the dose response and time course of scopolamine's effects, subjects were administered either low dose (6.1{dollar}\mu{dollar}g/kg, IV) or high dose (7.3{dollar}\mu{dollar}g/kg, IV) scopolamine. The high dose group manifested significant declines in global grey matter profusion, maximal at 25 minutes post-infusion, which were not observed in the low dose group. The greatest regional decline was observed in anterior cortex. Deficits in memory, but not attention were found in both groups. The aspect of memory most impaired was the consistent retrieval of words from long term memory.;The efficacy of physostigmine and neostigmine (centrally and peripherally acting cholinesterase inhibitors, respectively) in reversing scopolamine's effects was examined, to assess the specificity of scopolamine's effects. Physostigmine (0.02mg/kg) or neostigmine (0.01mg/kg or 0.007mg/kg) was administered to coincide with the maximal scopolamine effect, 25 minutes post-infusion.;Physostigmine antagonized the further global and anterior reduction in rCBF from 5 to 25 minutes post-scopolamine administration. Global and anterior CBF continued to decline after neostigmine administration. The memory impairment persisted after administration of both agents and again, consistent retrieval was most affected.;Cholinergic antagonism exerts widespread influence on cerebral perfusion and mnestic function and may influence the central nervous system by interacting with other neurotransmitter systems.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
