Langston Jeffrey L, Adkins Angela L, Moran Anita V, Rockwood Gary A, Deford Michelle S
Drug Assessment Division, US Army Medical Research Institute of Chemical Defense, MCMR-UV-DA, Aberdeen Proving Ground, MD 21010-5400, USA.
Neurotoxicol Teratol. 2005 Nov-Dec;27(6):841-53. doi: 10.1016/j.ntt.2005.06.015. Epub 2005 Jul 19.
The present study evaluated the dose-response effects of subacute exposure to sublethal doses of the organophosphorus (OP) chemical warfare nerve agent (CWNA) sarin (GB) on the operant behavior of guinea pigs. Dietary restricted guinea pigs, trained to respond for food under a progressive ratio (PR) schedule of reinforcement, were injected five times per week (Monday-Friday) for 2 weeks with fractions (0.1, 0.2, and 0.4) of the established LD(50) of GB (42 microg/kg). Changes in body weight, whole blood (WB) acetylcholinesterase (AChE) levels, and operant performances were monitored over the 2 weeks of GB exposure and for an additional 2 weeks following the termination of exposures. There were dose-related changes in body weight and WB AChE levels throughout the exposure and post-exposure periods. Several parameters of PR performance were disrupted during exposure to 0.4 LD50 GB, however, concurrent weight loss indicated the presence of overt toxicity. PR performance recovered following the termination of exposures. Lower doses (0.1 and 0.2 LD50) of GB failed to produce reliable effects on operant performance during the exposure period. Overall responding decreased during exposure to 0.4 LD50 GB, resulting in reduced response rates and break points. The decrease in overall response rates was attributed to an increase in pausing since there was no decrease in running rate. Motor effects of 0.4 LD50 GB were evident as an increase in the proportion of lever press durations > or = 1.0 s. In the present study, doses of GB lower than 0.4 LD50 produced no marked alteration of operant performance in guinea pigs, although WB AChE levels were maximally inhibited to 20% of control.
本研究评估了亚急性暴露于亚致死剂量的有机磷（OP）化学战神经毒剂（CWNA）沙林（GB）对豚鼠操作性行为的剂量反应效应。对饮食受限的豚鼠进行训练，使其在渐进比率（PR）强化程序下为获取食物做出反应，每周（周一至周五）注射5次，持续2周，注射剂量为已确定的GB半数致死剂量（LD50，42微克/千克）的几分之一（0.1、0.2和0.4）。在GB暴露的2周期间以及暴露终止后的另外2周内，监测体重、全血（WB）乙酰胆碱酯酶（AChE）水平和操作性行为表现的变化。在整个暴露期和暴露后期间，体重和WB AChE水平存在剂量相关变化。在暴露于0.4 LD50 GB期间，PR行为的几个参数受到干扰，然而，同时出现的体重减轻表明存在明显毒性。暴露终止后，PR行为表现恢复。较低剂量（0.1和0.2 LD50）的GB在暴露期间未能对操作性行为产生可靠影响。在暴露于0.4 LD50 GB期间，总体反应减少，导致反应率和断点降低。总体反应率的降低归因于停顿增加，因为奔跑速度没有降低。0.4 LD50 GB的运动效应表现为按压杠杆持续时间≥1.0秒的比例增加。在本研究中，低于0.4 LD50的GB剂量对豚鼠的操作性行为没有产生明显改变，尽管WB AChE水平被最大程度抑制至对照的20%。
