Stanton M E, Mundy W R, Ward T, Dulchinos V, Barry C C
Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Neurotoxicology. 1994 Spring;15(1):201-8.
On postnatal day 21 (PND21), Long-Evans rat pups received a single subcutaneous injection of either 0 (corn oil vehicle), 90, 120, or 240 mg/kg chlorpyrifos and were then tested for T-maze delayed alternation on PND23 or 26. Acetylcholinesterase (AChE) activity and muscaranic receptor density [i.e., quinuclidinyl benzilate (QNB) binding] were determined in hippocampus and cortex of brains taken from pups 15 hours after the end of behavioral testing (i.e., the morning of PND24, and 27). Pups exposed to the 240 mg/kg dose of chlorpyrifos showed signs of overt toxicity that precluded behavioral testing. Exposure to the 120 mg/kg dose produced a selective memory impairment (ie., a deficit in delayed alternation but not position discrimination) relative to the 90 mg/kg and vehicle groups. This impairment was transient, however, as it appeared on PND23 and was absent by PND26. PND21 exposure to chlorpyrifos produced dose-related inhibition and recovery of brain AChE over the PND24-27 age range. A similar pattern was observed in hippocampus. Binding of [3H]QNB was reduced in frontal cortex on PND27 only at the 240 mg/kg dose. No significant effects were observed in the hippocampus. These results suggest that the neurochemical effects of acute chlorpyrifos administration are more transient, and the behavioral effects are smaller and shorter-lived than what has been reported in adult rats.
在出生后第21天（PND21），Long-Evans大鼠幼崽皮下注射单次剂量为0（玉米油赋形剂）、90、120或240mg/kg的毒死蜱，然后在PND23或26进行T迷宫延迟交替试验。在行为测试结束后15小时（即PND24和27的上午），从幼崽大脑的海马体和皮质中测定乙酰胆碱酯酶（AChE）活性和毒蕈碱受体密度[即，樟柳碱（QNB）结合]。暴露于240mg/kg剂量毒死蜱的幼崽出现明显的毒性迹象，无法进行行为测试。相对于90mg/kg和赋形剂组，暴露于120mg/kg剂量导致选择性记忆障碍（即延迟交替缺陷，但位置辨别无缺陷）。然而，这种障碍是短暂的，因为它出现在PND23，到PND26时消失。PND21暴露于毒死蜱会在PND24 - 27年龄范围内产生与剂量相关的脑AChE抑制和恢复。在海马体中也观察到类似模式。仅在240mg/kg剂量下，PND27时额叶皮质中[3H]QNB的结合减少。在海马体中未观察到显著影响。这些结果表明，急性给予毒死蜱的神经化学效应更短暂，行为效应比成年大鼠中报道的更小且持续时间更短。
