Wolthuis O L, Philippens I H, Vanwersch R A
Medical Biological Laboratory TNO, Rijswijk, The Netherlands.
Pharmacol Biochem Behav. 1991 Aug;39(4):851-8. doi: 10.1016/0091-3057(91)90043-2.
Several earlier studies showed that, in contrast with DFP, repeated injections with soman did not lead to behavioral tolerance in rats. The reason for the difference between the effects of these two organophosphate cholinesterase inhibitors was not clear and a neurophysiological approach was undertaken. Four experiments (A, B, C and D) were carried out, each consisting of three groups of rats, SC injected with saline, DFP (600 micrograms/kg) or soman (60 micrograms/kg) respectively. In Experiment B and D the rats were trained to criterion in a two-way shuttlebox. Thereafter, the animals of Experiment B were fitted with suitable electrodes and two days later their EEGs and visual evoked responses (VERs) were recorded, 1 and 24 h after a single dose of the above-mentioned compounds. In Experiment D the trained animals were subsequently injected 3 times per week for 4 weeks with the same doses and their performance was tested 5 days per week, 1 and 24 h after injection. After those 4 weeks, when the DFP-treated animals had developed behavioral tolerance, electrodes were fitted and EEGs and VERs were recorded after two days, again 1 and 24 h after injection, as in Experiment B. The difference with Experiments A and C was that these animals were not trained. Otherwise, treatment schedules and recording procedures of Experiment A were identical to those of Experiments B and of Experiment C to those of Experiment D. In all cases the EEGs and VERs were recorded from animals slowly walking in a rotating hollow transparent wheel. The results show a similar pattern in all four experiments.(ABSTRACT TRUNCATED AT 250 WORDS)
几项早期研究表明,与二异丙基氟磷酸酯(DFP)不同,反复给大鼠注射梭曼不会导致行为耐受性。这两种有机磷酸酯胆碱酯酶抑制剂作用差异的原因尚不清楚,因此采用了神经生理学方法。进行了四个实验(A、B、C和D),每个实验都由三组大鼠组成,分别皮下注射生理盐水、DFP(600微克/千克)或梭曼(60微克/千克)。在实验B和D中,大鼠在双向穿梭箱中训练至标准。此后,实验B的动物安装了合适的电极,两天后记录它们在单次注射上述化合物后1小时和24小时的脑电图(EEG)和视觉诱发电位(VER)。在实验D中,训练过的动物随后每周注射3次,共4周,注射相同剂量,每周5天测试其行为表现,分别在注射后1小时和24小时进行。4周后,当DFP处理的动物产生行为耐受性时,安装电极,两天后记录脑电图和视觉诱发电位,同样在注射后1小时和24小时记录,与实验B相同。与实验A和C的不同之处在于,这些动物没有经过训练。否则,实验A的治疗方案和记录程序与实验B相同,实验C与实验D相同。在所有情况下,脑电图和视觉诱发电位都是在动物在旋转的空心透明轮中缓慢行走时记录的。所有四个实验的结果都呈现出相似的模式。(摘要截断于250字)