Timofeeva O A, Gordon C J
Curriculum in Toxicology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Brain Res. 2001 Mar 2;893(1-2):165-77. doi: 10.1016/s0006-8993(00)03309-6.
Organophosphates (OPs) inhibit acetylcholinesterase (AChE) activity causing cholinergic stimulation in the central nervous system (CNS). Cholinergic systems are crucial in electroencephalogram (EEG) generation and regulation of behavior; however, little is known about how OP exposure affects the EEG and behavioral states. We recorded EEG, core temperature and motor activity before and after exposure to the OP pesticide chlorpyrifos (CHP) in adult female rats implanted with telemetric transmitters. The recording and reference electrodes were placed in the occipital and frontal bones, respectively. The animals received CHP, 25 mg/kg, p.o., or oxotremorine (OX), 0.2 mg/kg, s.c. CHP led to a significant increase in delta (0.1-3.5 Hz), slow theta (4-6.5 Hz), gamma 2 (35.5-50 Hz), reduction in fast theta (7-8.5 Hz), alpha/sigma (9-14 Hz), beta 1 (14.5-24 Hz), beta 2 (24.5-30 Hz) and gamma 1 (30.5-35 Hz) powers, slowing of peak frequencies in 1-9 Hz range, hypothermia and decrease in motor activity. The drop in 7-14 Hz was associated with cholinergic suppression of sleep spindles. Changes in behavioral state were characterized by dramatic diminution of sleep postures and exploring activity and prolongation of quiet waking. There was recovery in all bands in spite of continued inhibition of AChE activity [44,45] in rats exposed to CHP. OX-induced EEG and behavioral alterations were similar to CHP except there was no increase in delta and the onset and recovery were more rapid. We did not find a correlation between the EEG and core temperature alterations. Overall, changes in EEG (except in delta band) and behavior following CHP were attributable to muscarinic stimulation. Cortical arousal together with increased quiet waking and decreased sleep after CHP occurred independently from inhibition of motor activity and lowering of core temperature.
有机磷酸酯(OPs)抑制乙酰胆碱酯酶(AChE)活性,导致中枢神经系统(CNS)出现胆碱能刺激。胆碱能系统在脑电图(EEG)生成和行为调节中至关重要;然而,关于接触OPs如何影响EEG和行为状态却知之甚少。我们在植入遥测发射器的成年雌性大鼠中,记录了接触OP农药毒死蜱(CHP)前后的EEG、核心体温和运动活动。记录电极和参考电极分别置于枕骨和额骨。动物接受口服25mg/kg的CHP或皮下注射0.2mg/kg的氧化震颤素(OX)。CHP导致δ波(0.1 - 3.5Hz)、慢θ波(4 - 6.5Hz)、γ2波(35.5 - 50Hz)显著增加,快θ波(7 - 8.5Hz)、α/σ波(9 - 14Hz)、β1波(14.5 - 24Hz)、β2波(24.5 - 30Hz)和γ1波(30.5 - 35Hz)功率降低,1 - 9Hz范围内的峰值频率减慢,体温过低以及运动活动减少。7 - 14Hz的下降与胆碱能对睡眠纺锤波的抑制有关。行为状态的变化表现为睡眠姿势和探索活动显著减少,安静觉醒时间延长。尽管接触CHP的大鼠中AChE活性持续受到抑制[44,45],但所有频段均出现了恢复。OX诱导的EEG和行为改变与CHP相似,只是δ波没有增加,且发作和恢复更快。我们未发现EEG和核心体温改变之间存在相关性。总体而言,CHP后EEG(δ频段除外)和行为的变化归因于毒蕈碱刺激。CHP后皮质觉醒以及安静觉醒增加和睡眠减少独立于运动活动抑制和核心体温降低而发生。