Department of New Drug Evaluation, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing, Haidian District, PR China.
Neurotoxicology. 2011 Aug;32(4):355-61. doi: 10.1016/j.neuro.2011.03.008. Epub 2011 Mar 29.
Chlorpyrifos (CPF) is a broad spectrum, highly effective organophosphorus (OP) pesticide that has been largely used worldwide. Over the past decades, numerous studies have assessed the potential neurotoxic effects of either acute or chronic exposure to CPF on developing brain. Despite being an acetylcholinersterase inhibitor, the effects of CPF are not only confined to cholinergic system, but are involved in a wide variety of neurotransmitter systems, especially the serotonin (5-HT) system, which leads to long-lasting changes in 5-HT-related emotional behaviors. In our present study, 4-week-old adolescent male Sprague-Dawley rats were repeatedly exposed to CPF at daily doses of 10, 20, 40, 80, and 160 mg/kg/day (s.c., 7 days), and then subjected to a battery of emotional behavioral tests that related to serotonergic function in order to determine CPF effects in adolescent rats. Results in behavioral tests demonstrated CPF significantly increased the entries to and time spent in the open arms in the elevated plus-maze test at the dose of 40-160 mg/kg, the number of shocks in the Vogel's conflict test at the dose of 20-160 mg/kg, and significantly decreased the latency to feed in the novelty-suppressed feeding test in both dose range. Interestingly, in the forced swimming test, at the dose of 10mg/kg, CPF significantly increased the immobility time, whereas it significantly decreased the immobility time at the dose of 160 mg/kg. Our data suggest that repeated exposure to CPF elicits alterations of the emotional behaviors related to serotonergic nervous system in adolescent male rats. However, the underlying mechanism needs further investigations.
毒死蜱(CPF)是一种广谱、高效的有机磷(OP)农药,在世界范围内得到了广泛应用。在过去的几十年中,许多研究评估了急性或慢性接触 CPF 对发育中大脑的潜在神经毒性作用。尽管 CPF 是一种乙酰胆碱酯酶抑制剂,但它的作用不仅限于胆碱能系统,还涉及多种神经递质系统,特别是 5-羟色胺(5-HT)系统,这导致 5-HT 相关情绪行为的持久变化。在我们目前的研究中,4 周龄的青春期雄性 Sprague-Dawley 大鼠每天接受 CPF 重复暴露,剂量分别为 10、20、40、80 和 160mg/kg/天(sc,7 天),然后进行一系列与 5-HT 功能相关的情绪行为测试,以确定 CPF 对青春期大鼠的影响。行为测试结果表明,CPF 显著增加了高架十字迷宫测试中进入和停留在开放臂的次数和时间,在 20-160mg/kg 剂量下的沃格氏冲突测试中的电击次数,以及在新奇抑制进食测试中两个剂量范围内的进食潜伏期显著缩短。有趣的是,在强迫游泳测试中,10mg/kg 的 CPF 显著增加了不动时间,而 160mg/kg 的 CPF 则显著减少了不动时间。我们的数据表明,重复接触 CPF 会引起青春期雄性大鼠与 5-HT 能神经系统相关的情绪行为改变。然而,其潜在机制需要进一步研究。