Persistent behavioral consequences of neonatal chlorpyrifos exposure in rats
Persistent behavioral consequences of neonatal chlorpyrifos exposure in rats
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DOI：
10.1016/s0165-3806(01)00215-2
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发表时间：
2001-09-23
期刊：
影响因子：
--
通讯作者：
Slotkin, TA
中科院分区：
文献类型：
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作者：
Levin, ED;Addy, N;Slotkin, TA
毒死蜱(CPF)是一种广泛使用的杀虫剂，已被证明能改变脑细胞的发育。本研究旨在探讨大鼠生后早期[1 mg/kg/d生后1~4天]或晚期(5 mg/kg/d，11~14天)CPF暴露是否具有持续性行为效应。我们测试了T形迷宫中的自发交替，8字形装置中的运动活动，以及从青春期到成年期的16臂放射状迷宫中的学习。在任何一个新生儿期暴露都会对认知行为产生显著的长期影响。在放射臂迷宫中，正如前面已经看到的，对照雄性比对照雌性表现得更准确。出生后早期的CPF暴露逆转了这一效应。在PND 1-4上暴露，CPF组的雌性在径向迷宫中的工作和参考记忆错误减少，将她们的错误率降低到对照组男性；相反，在训练的初始阶段，暴露于CPF的雄性表现出错误的增加。当动物暴露在PND 11-14上，然后在青春期和成年期进行测试时，雄性在T迷宫中的反应潜伏期显著减慢，在8字形装置中的习惯化速度在两性中都减慢了。当女性受到毒扁豆碱拮抗剂东莨菪碱的剧烈刺激时，她们没有表现出参照记忆的损害，而对照组有；这些结果表明，在CPF暴露后发生了适应，导致了毒碱胆碱能对参照记忆的控制丧失。而烟碱型胆碱能拮抗剂(甲戊胺)则没有这种变化。这些结果表明，早期新生儿暴露于CPF会导致认知能力的长期变化，与以前看到的神经化学变化一致，具有明显的性别选择性。其他缺陷可能会通过类似的策略来揭示，这些策略使动物受到尖锐的挑战，从而揭示了维持基本表现的适应机制。(C)2001爱思唯尔科学公司保留所有权利。
Chlorpyrifos (CPF) is a widely used insecticides which has been shown to alter brain cell development. The current project was conducted to determine whether there are persistent behavioral effects of early [1 mg/kg/day postnatal days (PNDs) 1-4] or late (5 mg/kg/day PNDs 11-14) postnatal CPF exposure in rats. We tested spontaneous alternation in a T-maze, locomotor activity in the Figure-8 apparatus and learning in the 16-arm radial maze, throughout adolescence and into adulthood. Exposure during either neonatal period elicited significant long-term effects on cognitive behavior. In the radial-arm maze, as has been seen previously, control male performed more accurately than control females. Early postnatal CPF exposure reversed this effect. With exposure on PNDs 1-4, females in the CPF group showed a reduction in working and reference memory errors in the radial maze, reducing their error rate to that seen in control males; in contrast, CPF-exposed males exhibited an increased in errors during the initial stages of training. When animals were exposed on PNDs 11-14 and then tested in adolescence and adulthood, males showed a significant slowing of response latency in the T-maze and the rate of habituation in the Figure-8 apparatus was slowed in both sexes. When females were challenged acutely with the muscarinic antagonist, scopolamine, they did not show reference memory impairment, whereas controls did;, these results suggest that adaptations occur after CPF exposure that lead to loss of muscarinic cholinergic control of reference memory. No such changes were seen with a nicotinic cholinergic antagonist (mecamylamine). These results indicate that early neonatal exposure to CPF induces long-term changes in cognitive performance that, in keeping with the neurochemical changes seen previously, are distinctly gender-selective. Additional defects may be revealed by similar strategies that subject the animals to acute challenges, thus uncovering the adaptive mechanisms that maintain basal performance. (C) 2001 Elsevier Science BY All rights reserved.