Comparison of Extracellular Striatal Acetylcholine and Brain Seizure Activity Following Acute Exposure to the Nerve Agents Cyclosarin and Tabun in Freely Moving Guinea Pigs

Organophosphorus nerve agents like cyclosarin and tabun are potent cholinesterase inhibitors. The inhibition of acetylcholinesterase, which is responsible for breaking down acetylcholine (ACh) at the synapse and neuromuscular junction, leads to a build-up of extracellular ACh and a series of toxic c...

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Bibliographic Details
Main Authors: O'Donnell, John C, Acon-Chen, Cindy, McDonough, John H, Shih, Tsung-Ming
Format: Report
Language:English
Subjects:
ACETYLCHOLINE
ACH(ACETYLCHOLINE)
ACHE(ACETYLCHOLINESTERASE)
AMINO ACIDS
AMN(ATROPINE METHYL NITRATE)
Anatomy and Physiology
ATROPINE
BLOOD
BRAIN
CHE(CHOLINESTERASE)
Chemical, Biological and Radiological Warfare
CHOLINESTERASE
CYCLOSARIN
DIALYSIS
EAA(EXCITATORY AMINO ACIDS)
ELECTROENCEPHALOGRAPHY
GA AGENT
GRAPHS
GUINEA PIGS
HPLC(HIGH PERFORMANCE LIQUID CHROMATOGRAPHY)
IN VIVO ANALYSIS
LETHALITY
LIQUID CHROMATOGRAPHY
NERVE AGENTS
NITRATES
ORGANIC PHOSPHORUS COMPOUNDS
ORGANOPHOSPHORUS COMPOUNDS
Pharmacology
REPRINTS
SEIZURE ACTIVITY
STATISTICAL ANALYSIS
STRIATAL IN VIVO MICRODIALYSIS COLLECTION
TABLES(DATA)
TABUN
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Summary:Organophosphorus nerve agents like cyclosarin and tabun are potent cholinesterase inhibitors. The inhibition of acetylcholinesterase, which is responsible for breaking down acetylcholine (ACh) at the synapse and neuromuscular junction, leads to a build-up of extracellular ACh and a series of toxic consequences including hypersecretion, tremor, convulsion/seizure, respiratory distress, coma, and death. This study employed simultaneous and continuous electroencephalographic recording and striatal microdialysis collection for quantification of ACh changes (via subsequent HPLC analysis) during acute exposure to a 1.0 LD50 subcutaneous dose of either cyclosarin or tabun to investigate differences in cholinergic and behavioral effects. Information about the unique mechanisms and consequences of different nerve agents is intended to aid in the development of broad-spectrum medical countermeasures for nerve agents. At the dose administered, non-seizure and sustained seizure responses were observed in both agent groups and in the tabun-exposed group some subjects experienced an unsustained seizure response. Significant extracellular ACh increases were only observed in seizure groups. Cyclosarin and tabun were found to exhibit some unique cholinergic and ictogenic characteristics. Lethality only occurred in subjects experiencing sustained seizure, and there was no difference in lethality between agent groups that progressed to sustained seizure. Published in Toxicology Mechanisms and Methods, v20 n9 p600-608, 2010.