Ricceri Laura, Markina Nadja, Valanzano Angela, Fortuna Stefano, Cometa Maria Francesca, Meneguz Annarita, Calamandrei Gemma
Laboratorio di Fisiopatologia, Istituto Superiore di Sanità, Rome, Italy.
Toxicol Appl Pharmacol. 2003 Sep 15;191(3):189-201. doi: 10.1016/s0041-008x(03)00229-1.
Neonatal mice were treated daily on postnatal days (pnds) 1 through 4 or 11 through 14 with the organophosphate pesticide chlorpyrifos (CPF), at doses (1 or 3 mg/kg) that do not evoke systemic toxicity. Brain acetylcholinesterase (AChE) activity was evaluated within 24 h from termination of treatments. Pups treated on pnds 1-4 underwent ultrasonic vocalization tests (pnds 5, 8, and 11) and a homing test (orientation to home nest material, pnd 10). Pups in both treatment schedules were then assessed for locomotor activity (pnd 25), novelty-seeking response (pnd 35), social interactions with an unfamiliar conspecific (pnd 45), and passive avoidance learning (pnd 60). AChE activity was reduced by 25% after CPF 1-4 but not after CPF 11-14 treatment. CPF selectively affected only the G(4) (tetramer) molecular isoform of AChE. Behavioral analysis showed that early CPF treatment failed to affect neonatal behaviors. Locomotor activity on pnd 25 was increased in 11-14 CPF-treated mice at both doses, and CPF-treated animals in both treatment schedules were more active when exposed to environmental novelty in the novelty-seeking test. All CPF-treated mice displayed more agonistic responses, and such effect was more marked in male mice exposed to the low CPF dose on pnds 11-14. Passive avoidance learning was not affected by CPF. These data indicate that developmental exposure to CPF induces long-term behavioral alterations in the mouse species and support the involvement of neural systems in addition to the cholinergic system in the delayed behavioral toxicity of CPF.
新生小鼠在出生后第1天至第4天或第11天至第14天，每天接受有机磷酸酯农药毒死蜱（CPF）处理，剂量为（1或3毫克/千克），该剂量不会引发全身毒性。在处理结束后24小时内评估脑乙酰胆碱酯酶（AChE）活性。在出生后第1 - 4天接受处理的幼崽在出生后第5天、第8天和第11天进行超声发声测试，并在出生后第10天进行归巢测试（对家巢材料的定向）。然后评估两个处理组的幼崽的运动活动（出生后第25天）、新奇寻求反应（出生后第35天）、与陌生同种个体的社交互动（出生后第45天）以及被动回避学习（出生后第60天）。CPF 1 - 4处理后AChE活性降低了25%，但CPF 11 - 14处理后未降低。CPF仅选择性地影响AChE的G(4)（四聚体）分子异构体。行为分析表明，早期CPF处理未能影响新生期行为。在两个剂量下，出生后第11 - 14天接受CPF处理的小鼠在出生后第25天的运动活动增加，并且在新奇寻求测试中，两个处理组接受CPF处理的动物在接触环境新奇事物时更活跃。所有接受CPF处理的小鼠都表现出更多的攻击性行为反应，并且这种效应在出生后第11 - 14天接受低剂量CPF处理的雄性小鼠中更为明显。被动回避学习不受CPF影响。这些数据表明，发育过程中接触CPF会在小鼠物种中诱导长期行为改变，并支持除胆碱能系统外，神经系统也参与了CPF的延迟行为毒性作用。
