Psychopharmacology

, Volume 105, Issue 3, pp 400–406 | Cite as

Differential sensitivity of CNS regions to acetylcholinesterase inhibition following chronic low-dose soman treatment in the rat

  • Thomas C. Howerton
  • Michael R. Murphy
  • Stephanie A. Miller
  • Stanley L. Hartgraves
Original Investigations

Abstract

Several discrete brain regions were analyzed for regional brain sensitivity to acetylcholinesterase (AChE) inhibition following administration of repeated low-dose soman (39 µg/kg, SC; once daily for 5 days). The same brain regions were also assayed on days 3 through 7 after the last injection of soman, to examine possible recovery of AChE. The observed regional brain sensitivity to AChE inhibition can be described in the following order: frontal cortex = piriform cortex > hippocampus = cerebellum = thalamus > striatum = hypothalamus. Most brain areas showed only a small recovery from this inhibition through the seventh day following the last soman injection. The progressive nature of the AChE inhibition during the week of soman administration and the failure to find a significant interaction between injection and day indicates that tolerance to soman exposure did not develop in this paradigm. The protocol described here appears to provide a useful method to study prophylactic measures for low-dose repeated soman exposure and evaluation of differential CNS inhibition and recovery from AChE inhibition.

Key words

Soman Cholinesterase Chronic exposure Low-dose Organophosphate Brain areas Time course Anticholinesterase CNS Cholinergic function 

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Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • Thomas C. Howerton
    • 1
  • Michael R. Murphy
    • 2
  • Stephanie A. Miller
    • 2
  • Stanley L. Hartgraves
    • 2
  1. 1.Systems Research Laboratories (A Division of Arvin/Calspan)USA
  2. 2.Radiofrequency Radiation Branch, Occupational and Environmental Health DirectorateArmstrong LaboratoryBrooks AFBUSA

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