Stress does not enable pyridostigmine to inhibit brain cholinesterase after parenteral administration

The peripherally acting cholinesterase inhibitor pyridostigmine was widely used during the Gulf War as a pretreatment against possible chemical warfar e attack. Following consistent reports on long-term illness among Gulf War veterans, pyridostigmine was examined for its possible long-term effects, T hese effects were suggested to be induced by the combination of pyridostigm ine administration and stress exposure that allowed this quaternary compoun d to enter the brain through stress induced changes in blood-brain barrier (BBB) permeability, Recently, pyridostigmine administration was demonstrate d to inhibit brain cholinesterase following acute stress in mice. However, the effect was not replicated under similar conditions in guinea pigs, Beca use of the significant implication of these findings, we tested brain choli nesterase (ChE) inhibition following the administration of pyridostigmine, or the tertiary carbamate physostigmine, with or without stress in mice. Di fferent experiments were performed to examine the contribution of gender, a ge (young and adults), stress (type and intensity), or strain (CD-1 and FVB /n) parameters. No inhibition of brain ChE was detected in any of these exp eriments. At the same time, physostigmine induced the expected decrease in brain ChE in all the experiments, Thus, we could not replicate the findings that suggest pyridostigmine can affect brain cholinesterase following stre ss. (c) 2000 Academic Press.