Interactions of Subsymptomatic Doses of Sarin with Pyridostigmine - Neurochemical, Behavioral, and Physiological

Abstract

This report describes the effects of treatment with low levels of the cholinesterase (ChE) inhibitors Sarin (0.5 LD50 s.c. 3 times weekly) and pyridostigmine bromide (PB, 80 mg/L in drinking water) alone or in combination for 3 weeks as compared with untreated controls. At 2, 4 and 16 weeks after exposure, the following tests were performed: (1) Conditioned avoidance response (CAR), a test of learning and memory; (2) measurements of arterial blood pressure, heart rate, and baroreceptor reflexes; (3) measurements of regional cerebral blood flow (rCBF). There was a significant decrease in whole blood and RBC cholinesterase activities during treatment that returned to normal between 2 to 3 weeks after treatment. CAR, arterial blood pressure, heart rate, and measurements of baroreceptor mechanism gain did not show significant differences between experimental groups. rCBF indicated significant enhancement of cerebral perfusion in neocortex (face, hindlimb, forelimb, and trunk areas, primary and secondary motor areas, auditory and visual cortex), with a few additional locations with significant elevation of rCBF in entorhinal, ectorhinal, and piriform cortex in animals treated with Sarin+PB 2 weeks after treatment. At 4 weeks after treatment, the same general pattern was found in animals treated with sarin, with more significant locations in piriform and retrosplenial cortex, as well as amygdala. Only few changes in rCBF were found at 16 weeks post-treatment in the three experimental groups. In conclusion, learning, memory and cardiovascular regulations of the animals under study were not altered by the treatments used. Changes in rCBF were observed for sarin, alone or in combination with PB, but did not persist beyond the fourth week after treatment.

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Document Details

Document Type
Technical Report
Publication Date
Mar 01, 2002
Accession Number
ADA416060

Entities

People

  • Donald J. Jenden
  • Oscar U. Scremin
  • Tsung-Ming Shih

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  • Arteries
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