Altered central monoamine response to D-amphetamine in rats chronically exposed to inorganic lead.

Altered central monoamine response to D-amphetamine in rats chronically exposed to inorganic lead.
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改变长期接触无机铅的大鼠对 D-苯丙胺的中枢单胺反应。

DOI:
10.1007/bf00964630
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发表时间:
1985
影响因子:
4.4
通讯作者:
Michaelson,IA
Michaelson,IA
中科院分区:
医学3区
文献类型:
--
作者:
Lasley,SM;Greenland,RD;Minnema,DJ;Michaelson,IA

文献摘要

相似文献

基于行为和神经化学的发现,对慢性无机铅(Pb)暴露引起的神经毒性机制的研究主要集中在中枢神经系统生物胺功能上。下面的研究检测了从出生开始长期暴露于铅的大鼠多巴胺(DA)和5-羟色胺(5-HT)神经元对d-安非他明(AMPH)反应的时间过程,以进一步研究先前工作涉及的神经化学机制。子代通过泌乳坝暴露于0.2%醋酸铅,断奶后饮用相同的饮水液。在120-140天,动物注射1.0 mg/kg s.c.的药物或生理盐水,并在不同的时间间隔后处死。在给药后20分钟,铅暴露动物伏隔核和纹状体的DA含量显著高于对照组,在给药后80分钟,当对照组DA浓度恢复正常时,仍显著高于基线值。这些数据表明,暴露大鼠amph诱导的DA合成增强。5-羟基吲哚乙酸(5-HIAA)含量在给予AMPH的大鼠的三个脑区显著增加,表明在这些区域补偿了单独暴露Pb所产生的5-HIAA值的降低。本研究结果加强了DA和5-HT神经元对相对低水平铅暴露敏感的假设。
Investigations of the mechanisms involved in the neurotoxicity resulting from chronic inorganic lead (Pb) exposure have centered on CNS biogenic amine function on the basis of behavioral and neurochemical findings. The following study examined the time course of the response of dopamine (DA) and 5-hydroxytryptamine (5-HT) neurons to d-amphetamine (AMPH) in rats chronically exposed to Pb from birth in order to further examine neurochemical mechanisms implicated by previous work. Offspring were exposed to 0.2% Pb acetate via the lactating dam and then weaned to the same drinking solution. At 120–140 days animals were injected with 1.0 mg/kg s.c. of the drug or with saline and sacrificed after various intervals. DA content in nucleus accumbens and corpus striatum in Pb-exposed animals was significantly higher than corresponding levels in controls at 20 minutes post-drug and remained significantly higher than baseline values at 80 minutes after the drug when DA concentrations in controls had returned to normal. These data suggest enhanced AMPH-induced DA synthesis in exposed rats. 5-Hydroxyindoleacetic acid (5-HIAA) content was significantly increased in three brain regions in exposed rats given AMPH compared to values in saline-injected exposed animals, indicating a compensation in these areas for the decreases in 5-HIAA values produced by Pb exposure alone. The results of this study reinforce the hypothesis that DA and 5-HT neurons are sensitive to relatively low levels of Pb exposure.