The organophosphorus insecticide chlorpyrifos (CPF) is suspected to cause developmental neurotoxicity in children leading to long term effects. Developmental exposure of rat pups to CPF at low levels disrupts degradation of the brain endocannabinoids through the inhibition of fatty acid amide hydrolase (FAAH) and decreases the reactivity of juvenile rats in an emergence test. In this study, we further investigated the effects of developmental CPF exposure on behavior but also included exposure to PF-04457845, a specific inhibitor of FAAH, for comparison of behavior altered by FAAH inhibition with behavior altered by CPF. Ten day old rat pups were exposed orally either to 0.5, 0.75, or 1.0 mg/kg CPF or 0.02 mg/kg PF-04457845 daily for 7 days. In an open field (day 23), the high CPF and PF-04457845 groups exhibited increased motor activity but no differences in the time spent in the field's center. In an elevated plus maze (day 29), all treatment groups had increased open arm activity but ethological behaviors associated with anxiety were not altered. Behaviors in the maze associated with increased general activity and exploratory drive were increased. Social interactions (day 36) were measured and all treatment groups exhibited increased levels of play behavior. The similarities in behavior between PF-04457845 and CPF suggest that enhanced endocannabinoid signaling during the exposure period plays a role in the persistent alteration of behavior observed following developmental CPF exposure.

中文翻译：

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毒死rif对幼年大鼠的脂肪酸酰胺水解酶的抑制作用导致青少年的探索行为和社交行为发生改变。

怀疑有机磷杀虫剂毒死rif（CPF）对儿童造成发育神经毒性，导致长期影响。大鼠幼犬低水平地暴露于CPF的发育暴露通过抑制脂肪酸酰胺水解酶（FAAH）破坏了脑内大麻素的降解，并在出苗试验中降低了幼年大鼠的反应性。在这项研究中，我们进一步研究了发育性CPF暴露对行为的影响，但也包括暴露于PF-04457845（FAAH的特异性抑制剂）中，以比较FAAH抑制作用与CPF改变行为之间的关系。每天将十日龄的幼崽口服0.5、0.75或1.0 mg / kg CPF或0.02 mg / kg PF-04457845，持续7天。在空旷的地方（第23天），高CPF和PF-04457845组的运动能力增强，但在运动中心的时间却没有差异。在高架迷宫中（第29天），所有治疗组的张开臂活动均增加，但与焦虑相关的行为学行为并未改变。迷宫中与一般活动和探索驱动力增加相关的行为有所增加。测量了社交互动（第36天），所有治疗组均表现出较高的游戏行为水平。PF-04457845和CPF之间行为的相似性表明，在暴露期间，增强的内源性大麻素信号在发育性CPF暴露后观察到的行为持续改变中起作用。所有治疗组的张开臂活动都增加了，但与焦虑相关的行为却没有改变。迷宫中与一般活动和探索驱动力增加相关的行为有所增加。测量了社交互动（第36天），所有治疗组均表现出较高的游戏行为水平。PF-04457845和CPF之间行为的相似性表明，在暴露期间，增强的内源性大麻素信号在发育性CPF暴露后观察到的行为持续改变中起作用。所有治疗组的张开臂活动都增加了，但与焦虑相关的行为却没有改变。迷宫中与一般活动和探索驱动力增加相关的行为有所增加。测量了社交互动（第36天），所有治疗组均表现出较高的游戏行为水平。PF-04457845和CPF之间行为的相似性表明，在暴露期间，增强的内源性大麻素信号在发育性CPF暴露后观察到的行为持续改变中起作用。测量了社交互动（第36天），所有治疗组均表现出较高的游戏行为水平。PF-04457845和CPF之间行为的相似性表明，在暴露期间，增强的内源性大麻素信号在发育性CPF暴露后观察到的行为持续改变中起作用。测量了社交互动（第36天），所有治疗组的游戏行为水平均升高。PF-04457845和CPF之间行为的相似性表明，在暴露期间，增强的内源性大麻素信号在发育性CPF暴露后观察到的行为持续改变中起作用。