Decreased anxiety in juvenile rats following exposure to low levels of chlorpyrifos during development.
Decreased anxiety in juvenile rats following exposure to low levels of chlorpyrifos during development.
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DOI：
10.1016/j.neuro.2015.11.016
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发表时间：
2017-03
期刊：
影响因子：
3.4
通讯作者：
Nail CA
中科院分区：
文献类型：
--
作者：
Carr RL;Armstrong NH;Buchanan AT;Eells JB;Mohammed AN;Ross MK;Nail CA
毒死蜱（CPF）暴露于大鼠断奶前晚期期间抑制内源性大麻素代谢酶脂肪酸水解酶（FAAH）和单酰基甘油脂肪酶（MAGL），导致其各自的底物花生四烯酸（AEA）和2-花生四烯酸甘油（2-AG）的积累。这种情况发生在1.0毫克/公斤，但在较低的剂量（0.5毫克/公斤），只有FAAH和AEA的影响，没有可测量的抑制胆碱酯酶（胆碱酯酶）或MAGL。内源性大麻素系统在神经系统发育中起重要作用，可能是CPF的重要发育靶点。内源性大麻素系统在焦虑的调节中起着重要作用，并且在较高剂量下，发育暴露于CPF会改变焦虑样行为。然而，目前尚不清楚暴露于低剂量的CPF，不抑制胆碱酯酶是否会导致任何持续的影响焦虑样行为。为了确定是否发生这种情况，10日龄大鼠幼仔每天经口灌胃暴露于玉米油或0.5、0.75或1.0 mg/kg CPF，持续7天。在最后一次CPF给药后12 h，1.0 mg/kg导致FAAH、MAGL和ChE的显著抑制，而0.5和0.75 mg/kg仅导致FAAH的显著抑制。在所有三个处理组中，AEA水平显著升高，棕榈酰乙醇胺和油酰乙醇胺也是FAAH的底物。0.75和1.0 mg/kg剂量组2-AG水平显著升高，但0.5 mg/kg剂量组无显著升高。在第25天，测量从黑暗容器进入高度照明的新开放视野的潜伏期作为焦虑的指标。与对照组相比，所有三个CPF治疗组在出现之前在黑暗容器中花费的时间显著更少，表明焦虑水平降低。这表明，重复断奶前暴露于不抑制脑胆碱酯酶的剂量的CPF可以诱导在断奶后早期可检测到的焦虑水平下降。
Exposure to chlorpyrifos (CPF) during the late preweanling period in rats inhibits the endocannabinoid metabolizing enzymes fatty acid hydrolase (FAAH) and monoacylglycerol lipase (MAGL), resulting in accumulation of their respective substrates anandamide (AEA) and 2-arachidonylglycerol (2-AG). This occurs at 1.0 mg/kg, but at a lower dosage (0.5 mg/kg) only FAAH and AEA are affected with no measurable inhibition of either cholinesterase (ChE) or MAGL. The endocannabinoid system plays a vital role in nervous system development and may be an important developmental target for CPF. The endocannabinoid system plays an important role in the regulation of anxiety and, at higher dosages, developmental exposure to CPF alters anxiety-like behavior. However, it is not clear whether exposure to low dosages of CPF that do not inhibit ChE will cause any persistent effects on anxiety-like behavior. To determine if this occurs, 10-day old rat pups were exposed daily for 7 days to either corn oil or 0.5, 0.75, or 1.0 mg/kg CPF by oral gavage. At 12 h following the last CPF administration, 1.0 mg/kg resulted in significant inhibition of FAAH, MAGL, and ChE, whereas 0.5 and 0.75 mg/kg resulted in significant inhibition of only FAAH. AEA levels were significantly elevated in all three treatment groups as were palmitoylethanolamide and oleoylethanolamide, which are also substrates for FAAH. 2-AG levels were significantly elevated by 0.75 and 1.0 mg/kg but not 0.5 mg/kg. On day 25, the latency to emerge from a dark container into a highly illuminated novel open field was measured as an indicator of anxiety. All three CPF treatment groups spent significantly less time in the dark container prior to emerging as compared to the control group, suggesting a decreased level of anxiety. This demonstrates that repeated preweanling exposure to dosages of CPF that do not inhibit brain ChE can induce a decline in the level of anxiety that is detectable during the early postweanling period.
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作者：
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