Repeated coadministrations of pyridostigmine bromide, DEET, and permethrin alter locomotor behavior of rats

Interactions of pyridostigmine bromide (PB), permethrin (PERM), and the insect repellent DEET (DEET) have been suggested as possible causes of Gulf War Syndrome (GWS) in humans. Open field locomotor studies have long been used in behavioral toxicology. Using male and female Sprague-Dawley rats, video-computer analyses, and the isobolographic method we have determined the effects on locomotor speed and thigmotaxis following repeated administration of single-, double-, or triple-drug or vehicle controls in an open field. The effects were measured 24 hours after 7 daily drug administrations. Single-drug administrations caused no significant effects. Double-drug administrations resulted in significant effects in the following cases: males given PB + DEET had a significantly slower locomotion rate; males given DEET + PERM had a significantly faster locomotion rate; females given PB + DEET had a significantly slower locomotion rate; and females given PB + PERM spent significantly more time in the center zone (less thigmotaxis). Triple-drug administration caused no significant effect. These results in comparison with behavioral studies in chickens and insects show certain similarities. The implications of the lasting effects on animal models are relevant to GWS in humans.