Effects of Repeated Injection of Sublethal Doses of Soman on Behavior and on Brain Acetylcholine and Choline Concentrations in the Rat

摘要

The effects of repeated administration of soman (60 ug/kg; 0.4 LD 50) on brain regional acetylcholine (ACh) and choline (Ch) levels and on water consumption, body weight and gross behavioral changes were examined. Rats were dosed once a week or three times a week and selected brain tissue examined at 24 hr after 2, 4 or 6 weeks of chronic dosing. During the 6-week period, there was no difference between control and soman-dosed rats in water consumption or body weight under either treatment regimen. The animals treated once a week exhibited no change in the levels of ACh or Ch in any of the brain areas when examined at the end of 2, 4 or 6 weeks, nor did they show any obvious signs of poisoning. In animals treated three times a week, the levels of ACh did not change, when measured at 2, 4 or 6 weeks; however, at the end of 6 weeks, the levels of Ch were significantly elevated in the brainstem, cerebral cortex, hippocampus, midbrain, and cerebellum (57%, 147%, 68%, 46%, and 91% respectively) but not in the striatum. Some of the soman-treated rats showed a hyperreactivity syndrome that consisted of an exaggerated reaction to mild tactile stimuli. These results suggest that Ch metabolism in neuronal membranes may be altered following repeated low dose soman exposure.