Bushnell P J, Rice D C
Neurotoxicology Division, United States Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Neurotoxicol Teratol. 1999 Jul-Aug;21(4):381-92. doi: 10.1016/s0892-0362(99)00006-9.
Evidence from humans suggests that cognitive dysfunction may result from perinatal exposure to polychlorinated biphenyls (PCBs), and the results of some animal research with PCBs have been interpreted in terms of possible impairment of attention. Long-Evans rats were fed 3,3',4,4',5-pentachlorobiphenyl (PCB 126), a coplanar congener, at doses of 0.25 or 1 microgram/kg/day [corrected] throughout gestation and nursing. Male offspring of these rats were trained as adults to perform 2 tests of attention for food reward. First, a cued target-detection task, modeled after Posner's covert orienting method for humans, was used to assess visuospatial attention. In this task, a visual target stimulus was presented in 1 visual hemifield on each trial, preceded either by a valid cue, an invalid cue, or no cue. A valid cue appeared in the same hemifield as the target, and an invalid cue appeared in the opposite hemifield. As expected, valid cues increased accuracy and speed of target detection and invalid cues decreased accuracy and speed; moreover, these effects were systematically related to changes in cue intensity and target duration. However, perinatal exposure to PCB 126 did not affect acquisition or performance of this task. The second task assessed sustained attention by means of a signal detection method in which a brief, spatially-constant but temporally unpredictable, visual signal indicated which of 2 responses would yield food. Varying the intensity of the signal greatly affected the probability of correctly reporting the signal. Perinatal exposure to PCB 126 did not affect acquisition of the response rule or performance of the task. Finally, all rats were challenged with chlordiazepoxide (CDP) at doses of 0, 3, 5, 8, or 12 mg/kg SC, 20 min before testing in the sustained attention task. In control rats, low doses (3, 5, and 8 mg/kg) of CDP reduced accuracy at low signal intensities only, suggesting an increase in visual threshold. The high dose of CDP reduced accuracy at all signal intensities and increased the false-alarm rate as well, suggesting an impairment of attention. The rats exposed perinatally to PCB 126 at 0.25 micrograms/kg [corrected] were unaffected by CDP, and those exposed to PCB 126 at 1 microgram/kg [corrected] showed a smaller decrement in performance after CDP than did the controls. Taken together, these data provide little support for the possibility that perinatal exposure to PCB 126 causes deficits in attention, but suggest that PCB 126 may alter GABA-mediated pathways in the CNS during development.
来自人类的证据表明,围产期接触多氯联苯(PCBs)可能导致认知功能障碍,一些关于PCBs的动物研究结果被解释为可能存在注意力受损。在整个妊娠期和哺乳期,给Long-Evans大鼠喂食3,3',4,4',5-五氯联苯(PCB 126,一种共面同系物),剂量为0.25或1微克/千克/天[已校正]。这些大鼠的雄性后代成年后接受训练,以进行两项获取食物奖励的注意力测试。首先,采用一种模仿人类波斯纳隐蔽定向方法的线索目标检测任务来评估视觉空间注意力。在这项任务中,每次试验在一个视觉半视野中呈现一个视觉目标刺激,之前要么有一个有效线索、一个无效线索,要么没有线索。有效线索出现在与目标相同的半视野中,无效线索出现在相反的半视野中。正如预期的那样,有效线索提高了目标检测的准确性和速度,无效线索降低了准确性和速度;此外,这些效应与线索强度和目标持续时间的变化系统相关。然而,围产期接触PCB 126并未影响该任务的习得或表现。第二项任务通过信号检测方法评估持续注意力,在该方法中,一个短暂的、空间恒定但时间不可预测的视觉信号指示两种反应中的哪一种会获得食物。改变信号强度极大地影响了正确报告信号的概率。围产期接触PCB 126并未影响反应规则的习得或任务表现。最后,在持续注意力任务测试前20分钟,所有大鼠分别接受0、3、5、8或12毫克/千克皮下注射氯氮卓(CDP)的挑战。在对照大鼠中,低剂量(3、5和8毫克/千克)的CDP仅在低信号强度下降低了准确性,表明视觉阈值增加。高剂量的CDP在所有信号强度下均降低了准确性,并增加了误报率,表明注意力受损。围产期以0.25微克/千克[已校正]接触PCB 126的大鼠不受CDP影响;以1微克/千克[已校正]接触PCB 126的大鼠在接受CDP后表现出比对照组更小的性能下降。综上所述,这些数据几乎不支持围产期接触PCB 126会导致注意力缺陷的可能性,但表明PCB 126可能在发育过程中改变中枢神经系统中γ-氨基丁酸介导的通路。