CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Post Box 80, MG Marg, Lucknow 226001, India.
Toxicol Lett. 2012 May 20;211(1):1-9. doi: 10.1016/j.toxlet.2012.02.012. Epub 2012 Feb 24.
In view of extensive uses of lambda-cyhalothrin, a new generation type II synthetic pyrethroid, human exposure is quite imminent. The present study has therefore been carried out to investigate effect of lambda-cyhalothrin on brain dopaminergic and serotonergic systems and functional alterations associated with them. Post-lactational exposure to lambda-cyhalothrin (1.0 mg/kg or 3.0 mg/kg body weight, p.o.) from PD22 to PD49 caused a significant decrease in the motor activity and rota-rod performance in rats on PD50 as compared to controls. Decrease in motor activity in lambda-cyhalothrin treated rats was found to persist 15 days after withdrawal of exposure on PD65 while a trend of recovery in rota-rod performance was observed. A decrease in the binding of ³H-Spiperone, known to label dopamine-D2 receptors in corpus striatum associated with decreased expression of tyrosine hydroxylase (TH)-immunoreactivity and TH protein was observed in lambda-cyhalothrin treated rats on PD50 and PD65 compared to controls. Increase in the binding of ³H-Ketanserin, known to label serotonin-2A receptors in frontal cortex was observed in lambda-cyhalothrin exposed rats on PD50 and PD65 as compared to respective controls. The changes were more marked in rats exposed to lambda-cyhalothrin at a higher dose (3.0 mg/kg) and persisted even 15 days after withdrawal of exposure. The results exhibit vulnerability of developing rats to lambda-cyhalothrin and suggest that striatal dopaminergic system is a target of lambda-cyhalothrin. Involvement of serotonin-2A receptors in the neurotoxicity of lambda-cyhalothrin is also suggested. The results further indicate that neurobehavioral changes may be more intense in case exposure to lambda-cyhalothrin continues.
鉴于新一代合成拟除虫菊酯 lambda-氯氟氰菊酯的广泛使用，人类接触的风险相当大。因此，本研究旨在调查 lambda-氯氟氰菊酯对脑多巴胺能和 5-羟色胺能系统的影响及其相关功能改变。从 PD22 到 PD49，产后暴露于 lambda-氯氟氰菊酯（1.0 mg/kg 或 3.0 mg/kg 体重，口服）导致大鼠在 PD50 时的运动活性和转棒试验表现明显低于对照组。在 PD65 停止暴露 15 天后，发现 lambda-氯氟氰菊酯处理大鼠的运动活性持续下降，而转棒试验表现有恢复的趋势。与对照组相比，在 PD50 和 PD65 时，lambda-氯氟氰菊酯处理大鼠纹状体中与酪氨酸羟化酶（TH）免疫反应性和 TH 蛋白减少相关的 ³H-螺哌隆结合减少，已知 ³H-螺哌隆可标记多巴胺-D2 受体。与对照组相比，在 PD50 和 PD65 时，lambda-氯氟氰菊酯暴露大鼠的额皮质中 ³H-酮色林结合增加，已知 ³H-酮色林可标记 5-羟色胺-2A 受体。在更高剂量（3.0 mg/kg）暴露的大鼠中，变化更为明显，甚至在停止暴露 15 天后仍持续存在。结果表明，发育中的大鼠易受 lambda-氯氟氰菊酯的影响，提示纹状体多巴胺能系统是 lambda-氯氟氰菊酯的靶标。还提示 5-羟色胺-2A 受体参与了 lambda-氯氟氰菊酯的神经毒性。结果还表明，如果继续接触 lambda-氯氟氰菊酯，神经行为变化可能更为剧烈。
