Shih T M, Lenz D E, Maxwell D M
Biochemical Pharmacology Branch, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5425.
Psychopharmacology (Berl). 1990;101(4):489-96. doi: 10.1007/BF02244227.
The effects of repeated exposure to a sublethal dose (60 micrograms/kg; 0.4 LD50) of soman on brain regional acetylcholine (ACh) and choline (Ch) levels, spinal cord cholinesterase (ChE) activity and on water consumption, body weight and gross behavioral changes were examined. Male rats were dosed once a week or three times a week and at 24 h after 2, 4 or 6 weeks of dosing, selected brain tissues and behavior were examined. 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 adapted to this exposure regimen well. They 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. The total ChE activity fluctuated between 70 and 100% of control. When treated three times a week, however, survivors (90%) of the soman-treated rats developed signs that progressed in severity to a hyper-reactivity syndrome which consisted of an exaggerated reaction to mild tactile stimuli. Brain ACh levels did not change and ChE activity showed inhibition of 40, 58 and 75% when measured at 2, 4 and 6 weeks, respectively. At the end of 6 weeks, the levels of Ch, except in the striatum, were significantly elevated in brainstem, cerebral cortex, hippocampus, midbrain, and cerebellum (52%, 147%, 68%, 46%, and 91%, respectively), indicating that Ch metabolism in neuronal membranes may be altered following more frequent low-dose soman exposures.
研究了反复暴露于亚致死剂量（60微克/千克；0.4 LD50）梭曼对脑区乙酰胆碱（ACh）和胆碱（Ch）水平、脊髓胆碱酯酶（ChE）活性以及饮水量、体重和总体行为变化的影响。雄性大鼠每周给药一次或三次，在给药2、4或6周后的24小时，检查选定的脑组织和行为。在6周期间，在两种治疗方案下，对照大鼠和梭曼给药大鼠在饮水量或体重方面没有差异。每周给药一次的动物很好地适应了这种暴露方案。在2、4或6周结束时检查时，它们在任何脑区的ACh或Ch水平均无变化，也没有显示出任何明显的中毒迹象。总ChE活性在对照的70%至100%之间波动。然而，当每周给药三次时，梭曼处理大鼠的幸存者（90%）出现了症状，严重程度逐渐发展为一种高反应性综合征，包括对轻度触觉刺激的过度反应。脑ACh水平没有变化，ChE活性在2、4和6周测量时分别显示出40%、58%和75%的抑制。在6周结束时，除纹状体外，脑干、大脑皮层、海马、中脑和小脑的Ch水平显著升高（分别为52%、147%、68%、46%和91%），表明在更频繁的低剂量梭曼暴露后，神经元膜中的Ch代谢可能会发生改变。
