Brief postnatal PBDE exposure alters learning and the cholinergic modulation of attention in rats
Brief postnatal PBDE exposure alters learning and the cholinergic modulation of attention in rats
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DOI：
10.1093/toxsci/kfi285
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发表时间：
2005-11-01
影响因子：
3.8
通讯作者：
Driscoll, LL
中科院分区：
文献类型：
--
作者：
Dufault, C;Poles, G;Driscoll, LL
多溴联苯醚(PBDEs)是通常用作阻燃剂的化学物质，在环境中普遍存在，并在人类和野生动物中生物积累。然而，人们对它们的潜在毒理学特性知之甚少。在本研究中，雄性Long-Evans大鼠从出生后第6天开始，口服商品多溴二苯醚混合物DE-71或玉米油1周，进行了一项视觉辨别任务和两项持续性注意任务。完成这些任务后，给大鼠注射毒扁豆碱拮抗剂东莨菪碱(0，0.01，0.03，0.05 mg/kg)，在第二次持续性注意任务测试前30min皮下注射。与对照组相比，暴露于DE-71的大鼠表现出学习障碍，但没有持续的注意力。从准确度的下降和遗漏错误的增加可以看出，东莨菪碱削弱了动物在对照组中检测到短暂视觉线索的能力。然而，暴露在DE-71中的大鼠对东莨菪碱对遗漏错误的影响是不敏感的，特别是在提示之前长时间延迟的试验中，这表明持续注意的胆碱能调节发生了变化。对于暴露于DE-71的大鼠，在没有药物的情况下缺乏持续的注意力缺陷，加上对东莨菪碱对持续注意力的影响不敏感，表明尽管这种多溴二苯醚混合物在胆碱能功能方面产生了持久的变化，但要么(1)这些变化的幅度不足以与行为相关，要么(2)这些变化导致的行为缺陷可以通过成年后代偿神经机制或反应策略的发展来克服。
Polybrominated diphenyl ethers (PBDEs), chemicals commonly used as flame retardants, are ubiquitous in the environment and bioaccumulate in humans and wildlife. However, little is known about their potential toxicological properties. In the present study, male Long-Evans rats orally administered the commercial PBDE mixture DE-71 or corn oil for 1 week, beginning at postnatal day (PND) 6, were tested on a visual discrimination task and two sustained attention tasks. After completion of these tasks, the rats were administered a drug challenge with the muscarinic antagonist scopolamine (0, 0.01, 0.03, 0.05 mg/kg), which was injected subcutaneously 30 min prior to testing on the second sustained attention task. The DE-71-exposed rats demonstrated deficits in learning but not in sustained attention when compared to controls. Scopolamine impaired the animals' ability to detect the brief visual cues in controls, as evidenced by decreases in accuracy and increases in omission errors. However, the DE-71-exposed rats were subsensitive to the effects of scopolamine on omission errors, particularly on trials in which a long delay preceded the cue, suggesting alterations in the cholinergic modulation of sustained attention. For the DE-71-exposed rats, the lack of sustained attention deficits in the absence of the drug, coupled with the subsensitivity to scopolamine's effects on sustained attention, suggest that although this PBDE mixture produced lasting alterations in cholinergic functioning, either (1) these alterations were not of sufficient magnitude to be behaviorally relevant, or (2) behavioral deficits resulting from these alterations were overcome by the development of compensatory neural mechanisms or response strategies in adulthood.