The Effects of Pyridostigmine Bromide and Permethrin, Alone or in Combination, on Response Acquisition in Male and Female Rats

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2000-08, Vol.66 (4), p.739-746
• Main Authors: Van Haaren, Frans, Cody, Bethany, Hoy, James B, Karlix, Janet L, Schmidt, Charles J, Tebbett, Ian R, Wielbo, Donna
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Brain Chemistry - drug effects; Cholinesterase inhibition; Cholinesterase Inhibitors - blood; Cholinesterase Inhibitors - pharmacology; Cognition - drug effects; Conditioning, Operant - drug effects; Female; Gulf War Illness; Injections, Intraperitoneal; Insecticides - blood; Insecticides - pharmacology; Learning; Lever press; Male; male and female rats; Medical sciences; Miscellaneous; Permethrin; Pyrethrins - blood; Pyrethrins - pharmacology; Pyridostigmine bromide; Pyridostigmine Bromide - blood; Pyridostigmine Bromide - pharmacology; Rats; Rats, Sprague-Dawley; Response acquisition; Sex Characteristics; Synergism; Toxicology
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/S0091-3057(00)00282-3

VAN HAAREN, F., B. CODY, J. B. HOY, J. L. KARLIX, C. SCHMIDT, I. R. TEBBETT AND D. WIELBO. The effects of pyridostigmine bromide and permethrin, alone or in combination, on response acquisition in male and female rats. PHARMACOL BIOCHEM BEHAV 66(4) 739–746, 2000.—It has been hypothesized that concurrent exposure to pyridostigmine bromide and permethrin may have contributed to the development of neurocognitive symptoms in Gulf War veterans. The present experiment was designed to investigate the effects of pyridostigmine bromide and permethrin alone, or in combination, on the acquisition of a novel response, one measure of normal cognitive functioning. Male and female Sprague–Dawley rats were treated with pyridostigmine 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 intraperitoneal injection of permethrin (0, 15, or 60 mg/kg) before they were exposed to an experimental session during which they could earn food by pressing a lever 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 rats than in male rats following the highest dose. Pyridostigmine bromide delayed response acquisition in male and female rats, and resulted in higher response rates on the inactive lever in female rats than in male rats. Although permethrin levels were higher in subjects treated with pyridostigmine bromide 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 be determined in future studies, as its effects on motor activity and/or gastro-intestinal motility may have affected response acquisition.