NEUROBEHAVIORAL TOXICOLOGY OF PYRETHROID INSECTICIDES

合成拟除虫菊酯是一种强效杀虫剂， 天然除虫菊酯杀虫剂。 在啮齿类动物中， 这些化合物在高浓度时会引起多动症和震颤， 剂量会发展成癫痫 此外，那些拟除虫菊酯， 含有α-氰基取代基的δ-甲基苯丙胺也产生大量的 流涎和舞蹈样动作。 在初步研究中， 发现拟除虫菊酯的神经毒性作用是起源的核心 并且通过影响几种神经递质系统的试剂而增强。 此外，兴奋性毒性剂红藻氨酸也有增强作用。 我们还发现，拟除虫菊酯降低了3H-红藻氨酸的结合， 老鼠的大脑 低剂量的拟除虫菊酯也降低了操作性 对食物强化的反应。 基于这些初步 通过观察，我们提出了两个假设。 (1)拟除虫菊酯 通过作用于兴奋性氨基酸受体发挥作用 神经递质或其类似物的影响，以及（2）低剂量的 拟除虫菊酯可使用操作性调节技术检测到。 为了 为了实现这些目标，我们建议研究拟除虫菊酯的影响， 在体外和体内对~3H-海人酸和~3H-谷氨酸结合的影响 老鼠的脑细胞膜 此外，我们亦会研究 用这些化合物对两种配体的结合进行长期治疗。 由于鳟鱼对拟除虫菊酯的影响比 哺乳动物，我们将比较对受体结合在鳟鱼脑的影响， 在哺乳动物大脑中。 低剂量（小于10%）的影响 LD 50）的拟除虫菊酯对操作性反应的影响将使用两种 范例 研究将采用可变间隔时间表进行， 食物强化和颅内自我刺激作为补充剂。 的 拟除虫菊酯类杀虫剂有望成为重要农业杀虫剂 未来的重要性，因此它们在环境中的存在将 大大增加。 建议中的研究旨在使我们能够 为了更好地了解这些化合物发挥其 神经毒性作用，并帮助确定其最低剂量限值 毒性

The synthetic pyrethroids are potent insecticides that are derivatives of natural pyrethrin-based insecticides. In rodents symptoms consisting of hyperactivity and tremors are produced by these compounds which at high doses can progress to seizures. In addition, those pyrethroids such as deltamethrine containing an Alpha-cyano substituent also produce profuse salivation and choreoathtoid movements. In preliminary studies, we have found that the neurotoxic effects of the pyrethroids are central in origin and are potentiated by agents affecting several neurotransmitter systems. In addition, there was potentiation by the excitotoxic agent kainic acid. We also found that the pyrethroids decreased the binding of 3H-kainate in the mouse brain. Low doses of the pyrethroids also decreased operant responding for food reinforcement in rats. Based on these preliminary observations, we propose to test two hypotheses. (1) That pyrethroids exert their effects by acting at receptors for excitory amino acid neurotransmitters or their analogs and (2) that effects of low doses of the pyrethroids are detectable using operant conditioning techniques. In order to accomplish these goals we propose to study the effects of pyrethroids both in vitro and in vivo on the binding of 3H-kainic acid and 3H-glutamate to rat brain membranes. In addition, we will also examine the effects of chronic treatment with these compounds on binding of the two ligands. Since trout are more sensitive to the effects of the pyrethroids than are mammals, we will compare the effects on receptor binding in trout brain to that in mammal brain. The effects of the low doses (less than 10% of the LD50) of the pyrethroids on operant responding will be examined using two paradigms. Studies will be conducted using a variable interval schedule of food reinforcement and intracranial self-stimulations as reinforcers. The synthetic pyrethroid insecticides promise to be of significant agricultural importance in the future and thus their presence in the environment will increase greatly. It is intended that the proposed studies will enable us to better understand the mechanisms by which these compounds exert their neurotoxic effects and help in ascertaining the lower dose limits of their toxicity.