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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 78 (1982), S. 170-175 
    ISSN: 1432-2072
    Keywords: Acetylcholine ; Choline ; Soman ; Organophosphate ; Anticholinesterase ; Toxicity ; Lethality ; CNS ; Brain areas ; Rats ; Gas chromatography ; Mass spectrometry ; Time course ; Cholinergic function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The time course of changes in rat brain levels of acetylcholine (ACh) and choline (Ch) was investigated following a single SC injection of soman (0.9 LD50, 120 μg/kg) to understand the relationship between central neurotransmitter alteration and soman toxicity. Of the animals exposed to the dose of soman, 46% died within 24 h, with maximum mortality occurring during the first 40 min following soman administration. In a second group, surviving rats were killed at various times after treatment by a beam of focused microwave radiation to the head, and ACh and Ch levels were determined by gas chromatography-mass spectrometry. Soman produced a maximal ACh elevation in the brain stem at 20 min (34.4%), in cerebellum at 40 min (51.9%), in cortex and striatum at 2 h (320.3% and 35.2%, respectively), and in hippocampus and midbrain at 3 h (94.5% and 56.8%, respectively). ACh levels remained above normal approximately 30 min in the brain stem; 2 h in the midbrain, cerebellum, and striatum; 8 h in the cortex; and 16 h in the hippocampus. Ch levels were elevated in all areas except the striatum. Ch maxima occurred at 10–40 min and returned to control levels approximately 3 h after injection. Results suggest that perturbation of ACh levels due to soman was not uniform throughout the brain and that soman toxicity may reflect ACh changes in multiple areas, rather than changes in any given area. These data further suggest a possible relationship between elevated Ch levels and soman toxicity.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Soman ; Organophosphorus compounds ; Cholinesterase inhibitors ; Repeated exposure ; Adaptation ; Acetylcholine ; Choline ; Cholinesterase activity ; Toxicity ; Hyper-reactivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of repeated exposure to a sublethal dose (60 µg/kg; 0.4 LD50) of soman on brain regional acetylcholine (ACh) and choline (Ch) levels, spinal cord cholinesterase (ChE) activity and on water consumption, body weight and gross behavioral changes were examined. Male rats were dosed once a week or three times a week and at 24 h after 2, 4 or 6 weeks of dosing, selected brain tissues and behavior were examined. During the 6-week period, there was no difference between control and soman-dosed rats in water consumption or body weight under either treatment regimen. The animals treated once a week adapted to this exposure regimen well. They exhibited no change in the levels of ACh or Ch in any of the brain areas when examined at the end of 2, 4 or 6 weeks, nor did they show any obvious signs of poisoning. The total ChE activity fluctuated between 70 and 100% of control. When treated three times a week, however, survivors (90%) of the somantreated rats developed signs that progressed in severity to a hyper-reactivity syndrome which consisted of an exaggerated reaction to mild tactile stimuli. Brain ACh levels did not change and ChE activity showed inhibition of 40, 58 and 75% when measured at 2, 4 and 6 weeks, respectively. At the end of 6 weeks, the levels of Ch, except in the striatum, were significantly elevated in brainstem, cerebral cortex, hippocampus, midbrain, and cerebellum (52%, 147%, 68%, 46%, and 91%, respectively), indicating that Ch metabolism in neuronal membranes may be altered following more frequent low-dose soman exposures.
    Type of Medium: Electronic Resource
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