The effects of pyridostigmine bromide and permethrin, alone or in combination, on response acquisition in male and female rats

It has been hypothesized that concurrent exposure to pyridostigmine bromide and permethrin may have contributed to the development of neurocognitive s ymptoms in Gulf War veterans. The present experiment was designed to invest igate the effects of pyridostigmine bromide and permethrin alone, or in com bination, on the acquisition of a novel response, one measure of normal cog nitive functioning. Male and female Sprague-Dawley rats were treated with p yridostigmine bromide (1.5 mg/kg/day, by gavage in a volume of 5 ml/kg) or its vehicle for 7 consecutive days. They then also received an intraperiton eal injection of permethrin (0, 15, or 60 mg/kg) before they were exposed t o an experimental session during which they could earn food by pressing a l ever in an operant chamber. Serum permethrin levels increased as a function of its dose, and were higher in rats treated with pyridostigmine bromide. Sex differences were observed as permethrin levels were higher in female ra ts than in male rats following the highest dose. Pyridostigmine bromide del ayed response acquisition in male and female rats, and resulted in higher r esponse rates on the inactive lever in female rats than in male rats. Altho ugh permethrin levels were higher in subjects treated with pyridostigmine b romide than in those treated with vehicle, there were no differences in the behavioral effects of permethrin. Whether or not these behavioral effects of pyridostigmine bromide are of central or peripheral origin will need to he determined in future studies, as its effects on motor activity and/or ga stro-intestinal motility may have affected response acquisition. (C) 2000 E lsevier Science Inc.