Mactutus C F, Fechter L D
Teratology. 1985 Feb;31(1):1-12. doi: 10.1002/tera.1420310102.
The effects of moderate (150 +/- 2 ppm) prenatal carbon monoxide (CO) exposure (maternal HbCO concentrations of 15.6 +/- 1.1%) on learning and memory were assessed in young and aged adult rats using a two-way active avoidance paradigm. In experiment 1, the prenatal CO-exposed rats at 120 days of age acquired a conditioned avoidance response equally well as control animals in a 100-trial session. However, following a 24-hr interval the CO-exposed rats failed to demonstrate significant retention of the task as indicated by the absence of significant improvement in performance over the indicated by the absence of significant improvement in performance over the previous day; control subjects did show significant retention. In experiment 2, in which 120-day-old animals received 50 training trials per day until a criterion of ten consecutive avoidance responses was met, the prenatal CO-exposed subjects again acquired the task as well as control animals. When tested for retention 28 days later, a significant memory impairment was again observed in terms of trials required to reattain the avoidance criterion as well as in total percent avoidance responding. In neither experiment did an analysis of initial or average latency to escape the footshock stimulus reveal any significant alterations. These latter results suggest that the observed performance impairment reflected a memory deficit and not a disruption of sensory, motor, or motivational factors. In experiment 3, prenatal CO-exposed rats approximately 1 year of age (300-360 days of age) showed impairment relative to air-exposed controls in both the original learning and retention of the two-way avoidance response. Again, however, there was no evidence for alterations in performance factors per se. Collectively these data indicate that while young adult rats prenatally exposed to 150 ppm CO demonstrate an associative deficit restricted to memory impairment, aged adults similarly exposed during the prenatal period display a more pronounced deficit similar to that recently reported for animals tested as juveniles. The importance of parametric manipulations in uncovering long-term toxicity is also discussed.
采用双向主动回避范式，评估了中度（150±2 ppm）产前一氧化碳（CO）暴露（母体HbCO浓度为15.6±1.1%）对年轻和老年成年大鼠学习和记忆的影响。在实验1中，120日龄的产前CO暴露大鼠在100次试验中获得条件回避反应的情况与对照动物一样好。然而，在间隔24小时后，CO暴露大鼠未能表现出对该任务的显著记忆保持，表现为与前一天相比，其表现没有显著改善；而对照动物则显示出显著的记忆保持。在实验2中，120日龄的动物每天接受50次训练试验，直至达到连续十次回避反应的标准，产前CO暴露的受试者再次与对照动物一样完成了该任务。在28天后进行记忆保持测试时，再次观察到显著的记忆损伤，表现为重新达到回避标准所需的试验次数以及总的回避反应百分比。在两个实验中，对逃避电击刺激的初始或平均潜伏期进行分析均未发现任何显著变化。后一组结果表明，观察到的表现损伤反映的是记忆缺陷，而非感觉、运动或动机因素的破坏。在实验3中，约1岁（300 - 360日龄）的产前CO暴露大鼠在双向回避反应的原始学习和记忆保持方面相对于空气暴露对照均表现出损伤。然而，同样没有证据表明表现因素本身发生了改变。总体而言，这些数据表明，虽然产前暴露于150 ppm CO的年轻成年大鼠表现出仅限于记忆损伤的联想缺陷，但产前同样暴露的老年成年大鼠表现出更明显的缺陷，类似于最近报道的幼年测试动物的情况。还讨论了参数操作在揭示长期毒性方面的重要性。
