Nostrandt A C, Padilla S, Moser V C
Curriculum in Toxicology, University of North Carolina, Chapel Hill 27599, USA.
Pharmacol Biochem Behav. 1997 Sep;58(1):15-23. doi: 10.1016/s0091-3057(96)00458-3.
Behavioral changes and tissue cholinesterase (ChE) inhibition were examined in animals treated with the commonly used insecticide chlorpyrifos. Adult male rats were dosed by gavage with 0, 10, 30, 60, or 100 mg/kg chlorpyrifos. Rats (n = 20/dose group) were evaluated using a functional observational battery (FOB) and an automated measure of motor activity. All rats were tested the day before dosing and at 3.5 h (the time of peak effect) after dosing; half of these (n = 10/dose) were sacrificed immediately after testing for tissue collection. The remaining rats were tested again at 24 h, followed by sacrifice. The following tissues were collected from each animal: half brain, individual brain areas from the other half of the brain (frontal cortex, hippocampus, striatum, hypothalamus, cerebellum, pons/medulla), retina, liver, heart, diaphragm, quadriceps femoris muscle, and blood (separated into whole blood, plasma, and erythrocytes). ChE activity was measured in all tissues, and muscarinic receptor density was assessed as quinuclidinyl benzilate (QNB) binding in all brain regions, heart, and retina. The lowest dose produced no behavioral effects but did produce significant ChE inhibition in most tissues at 3.5 h. Higher doses produced more ChE inhibition and cholinergic signs of toxicity. Partial recovery from behavioral effects was evident at 24 h, with little or no corresponding recovery of ChE activity. Apparent downregulation of muscarinic receptor density was noted only in striatum and pons/medulla of rats treated with the highest dose of chlorpyrifos. Correlations for behavioral and biochemical effects were generally poor because: a) the low-dose effects on ChE inhibition were not reflected in behavioral signs, and b) behavioral signs showed recovery at 24 h, whereas ChE activity did not. Examination of data for individual rats indicated that > 60% of brain ChE inhibition was reached before neurobehavioral effects were evident.
对用常用杀虫剂毒死蜱处理的动物进行了行为变化和组织胆碱酯酶（ChE）抑制作用的研究。成年雄性大鼠经口灌胃给予0、10、30、60或100mg/kg毒死蜱。使用功能观察组合（FOB）和运动活动自动测量方法对大鼠（每组n = 20）进行评估。所有大鼠在给药前一天以及给药后3.5小时（效应峰值时间）进行测试；其中一半（每组n = 10）在测试后立即处死以收集组织。其余大鼠在24小时后再次测试，随后处死。从每只动物收集以下组织：半脑、另一半脑的各个脑区（额叶皮质、海马体、纹状体、下丘脑、小脑、脑桥/延髓）、视网膜、肝脏、心脏、膈肌、股四头肌以及血液（分离成全血、血浆和红细胞）。测量所有组织中的ChE活性，并评估所有脑区、心脏和视网膜中作为樟柳碱（QNB）结合的毒蕈碱受体密度。最低剂量未产生行为影响，但在3.5小时时在大多数组织中确实产生了显著的ChE抑制作用。较高剂量产生了更多的ChE抑制作用和胆碱能毒性体征。在24小时时行为影响有明显的部分恢复，而ChE活性几乎没有相应恢复。仅在给予最高剂量毒死蜱的大鼠的纹状体和脑桥/延髓中观察到毒蕈碱受体密度明显下调。行为和生化效应之间的相关性通常较差，原因如下：a）低剂量对ChE抑制的影响未在行为体征中体现，b）行为体征在24小时时显示恢复，而ChE活性未恢复。对个体大鼠数据的检查表明 > 60% 的脑ChE抑制在神经行为影响明显之前就已达到。
