RT Journal Article
SR Electronic
T1 Persistently Exaggerated Startle Responses in Rats Treated with Pyridostigmine Bromide
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1020
OP 1028
VO 287
IS 3
A1 Richard J. Servatius
A1 John E. Ottenweller
A1 Dawn Beldowicz
A1 Weidun Guo
A1 Guanping Zhu
A1 Benjamin H. Natelson
YR 1998
UL http://jpet.aspetjournals.org/content/287/3/1020.abstract
AB Troops in the Persian Gulf War have registered complaints consistent with CNS dysfunction that emerged after returning from the Gulf. A common experience among Persian Gulf War veterans was exposure to pyridostigmine bromide (PB) for prophylaxis against nerve gas exposure. To determine whether PB causes emergent CNS dysfunction, Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats were given PB for 7 consecutive days in their drinking water. The WKY, but not the SD, rats exhibited a delayed-onset, persistently exaggerated startle response. The WKY rats exhibited exaggerated startle responses that appeared 15 days after the end of PB treatment and were still evident 22 days after the end of treatment. Both the duration and the magnitude of the exaggerated startle responses were related to the dosage of PB. The PB-treated rats exhibited normal short-term and long-term habituation. However, exaggerated 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 that appeared sooner and dissipated faster than was evident after the first PB treatment. Inasmuch as the WKY rat has inherently low butyrylcholinesterase activity, a scavenger for PB, these results suggest that prophylactic PB may influence CNS function in individuals with low butyrylcholinesterase activity. Elaboration of the factors that mediate enhanced sensitization in the WKY rat may provide insight into some of the complaints registered by veterans of the Persian Gulf War. The American Society for Pharmacology and Experimental Therapeutics