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孕期和产后暴露于阿莫曲坦对雄性和雌性大鼠脑区去甲肾上腺素、5-羟色胺和多巴胺水平的影响。

Effects of prenatal and postnatal exposure to amitraz on norepinephrine, serotonin and dopamine levels in brain regions of male and female rats.

机构信息

Department of Toxicology and Pharmacology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain.

出版信息

Toxicology. 2011 Sep 5;287(1-3):145-52. doi: 10.1016/j.tox.2011.06.009. Epub 2011 Jun 17.

Abstract

The effects of maternal exposure to amitraz on brain region monoamine levels of male and female offspring rats at 60 days of age were observed. Maternal and offspring body weight, physical and general activity development were unaffected by the exposure of dams to amitraz (20mg/kgbw, orally on days 6-21 of pregnancy and 1-10 of lactation). Male and female offspring were sacrificed at 60 days of age and possible alterations in the content and metabolism of NE, DA and 5-HT were determined in brain regions by HPLC. The results showed that all these neurotransmitter systems were altered in a brain regional-related manner. In male and female offspring, amitraz induced a significant decrease in the prefrontal cortex 5-HT and its metabolite 5-HIAA and DA and its metabolites DOPAC and HVA levels with interaction of sex. Nevertheless, we verified that striatum DA and 5-HT and corresponding metabolite contents decreased in male and female offspring without statistical distinction of sex. In contrast, amitraz did not modify 5-HT content, but caused an increase in 5-HIAA content in the medulla oblongata and hippocampus in male and female offspring. Alterations in the hippocampus DA, DOPAC and HVA levels after amitraz exposure were also observed displaying a sex interaction. NE levels also showed a decrease after amitraz treatment in the prefrontal cortex and striatum without statistical sex interaction, but MHPG levels decreased in both regions with a sex interaction. Amitraz evoked increases in 5-HT turnover in the prefrontal cortex as well as in DA turnover in the striatum and hippocampus but decreases in NE turnover in the hypothalamus, prefrontal cortex and striatum. The present findings indicated that maternal exposure to amitraz altered noradrenergic, serotonergic and dopaminergic neurochemistry in their offspring in the prefrontal cortex, striatum and hippocampus, and those variations could be related to several alterations in the functions in which these brain regions are involved.

摘要

观察了母体暴露于阿莫曲坦对 60 日龄雄性和雌性仔鼠脑区单胺水平的影响。母体和仔鼠体重、身体和一般活动发育不受母体暴露于阿莫曲坦(20mg/kgbw,在妊娠第 6-21 天和哺乳期第 1-10 天口服)的影响。雄性和雌性仔鼠在 60 日龄时处死,通过 HPLC 测定脑区中 NE、DA 和 5-HT 的含量和代谢变化。结果表明,所有这些神经递质系统都以与脑区相关的方式发生改变。在雄性和雌性仔鼠中,阿莫曲坦诱导前额皮质 5-HT 及其代谢物 5-HIAA 和 DA 及其代谢物 DOPAC 和 HVA 水平显著降低,且存在性别交互作用。然而,我们证实,无论性别有无统计学差异,纹状体 DA 和 5-HT 及其相应代谢物含量均降低。相反,阿莫曲坦不改变 5-HT 含量,但引起雄性和雌性仔鼠延髓和海马 5-HIAA 含量增加。阿莫曲坦暴露后,海马 DA、DOPAC 和 HVA 水平也发生变化,表现出性别交互作用。NE 水平在暴露于阿莫曲坦后也在前额皮质和纹状体下降,但 MHPG 水平在两个区域均下降,且存在性别交互作用。阿莫曲坦在前额皮质引起 5-HT 周转率增加,在纹状体和海马引起 DA 周转率增加,但在下丘脑、前额皮质和纹状体引起 NE 周转率下降。本研究结果表明,母体暴露于阿莫曲坦改变了其仔鼠前额皮质、纹状体和海马中的去甲肾上腺素能、5-羟色胺能和多巴胺能神经化学,这些变化可能与这些脑区参与的几种功能的改变有关。

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