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

Several discrete brain regions were analyzed for regional brain sensitivity to acetylcholinesterase (AChE) inhibition following administration of repeated low-dose soman (39 micrograms/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 greater than hippocampus = cerebellum = thalamus greater than 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.