We tested the hypothesis that
pyridostigmine bromide (PB) intake and/or low-level
sarin exposure, suggested by some as causes of the symptoms experienced by Persian Gulf War veterans, induce neurobehavioral dysfunction that outlasts their effects on
cholinesterase. Adult male Sprague-Dawley rats were treated during 3 weeks with s.c. saline, PB in
drinking water (80 mg/l),
sarin (62.5 microg/kg; 0.5x LD(50), three times/week s.c.), or PB in
drinking water +
sarin. Animals were tested for passive avoidance, nociceptive threshold, acoustic startle, and open field activity 2, 4, or 16 weeks
after treatment. Two weeks after
sarin, acoustic startle was enhanced, whereas distance explored in the open field decreased. These effects were absent with PB +
sarin or PB by itself. No effect on any variable was found at 4 weeks, whereas at 16 weeks
sarin induced a decrease and PB +
sarin induced an increase in habituation in the open field test. Nociceptive threshold was elevated in the PB +
sarin group at 16 weeks. No effect of treatment on passive avoidance was noted in any group. Brain regional
acetylcholinesterase and cholineacetyltransferase activities were not affected at any time
after treatment, but
muscarinic receptors were down-regulated in hippocampus, caudate putamen, and mesencephalon in the
sarin group at 2 weeks. In conclusion, this study gives further support to the use of PB against
nerve agent poisoning and does not support the hypothesis that delayed symptoms experienced by Persian Gulf War veterans could be due to PB, alone or in association with low-level
sarin exposure.