Persistently exaggerated startle responses in rats treated with pyridostigmine bromide

Troops in the Persian Gulf War have registered complaints consistent with C NS dysfunction that emerged after returning from the Gulf. A common experie nce among Persian Gulf War veterans was exposure to pyridostigmine bromide (PB) for prophylaxis against nerve gas exposure. To determine whether PB ca uses emergent CNS dysfunction, Wistar-Kyoto (WKY) and Sprague-Dawley (SD) r ats were given PB for 7 consecutive days in their drinking water. The WKY, but not the SD, rats exhibited a delayed-onset, persistently exaggerated st artle response. The WKY rats exhibited exaggerated startle responses that a ppeared 15 days after the end of PB treatment and were still evident 22 day s after the end of treatment. Both the duration and the magnitude of the ex aggerated startle responses were related to the dosage of PB. The PB-treate d rats exhibited normal short-term and long-term habituation. However, exag gerated startle responses were related to the development of enhanced short -term sensitization. Treating the rats for a second time, 7 weeks after the end of the first PB treatment, induced an exaggerated startle response tha t appeared sooner and dissipated faster than was evident after the first PB treatment. Inasmuch as the WKY rat has inherently low butyrylcholinesteras e activity, a scavenger for PB, these results suggest that prophylactic PB may influence CNS function in individuals with low butyrylcholinesterase ac tivity. Elaboration of the factors that mediate enhanced sensitization in t he WKY rat may provide insight into some of the complaints registered by ve terans of the Persian Gulf War.