A re-evaluation of the neurotransmitter basis of chemotherapy-induced immediate and delayed vomiting: Evidence from the least shrew
A re-evaluation of the neurotransmitter basis of chemotherapy-induced immediate and delayed vomiting: Evidence from the least shrew
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DOI：
10.1016/j.brainres.2008.10.063
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发表时间：
2009-01-12
期刊：
影响因子：
2.9
通讯作者：
Ramirez, Juan
中科院分区：
文献类型：
--
作者：
Darmani, Nissar A.;Crim, Jennifer L.;Ramirez, Juan
虽然化疗诱导呕吐（CIV）的神经递质基础被认为是多因素的，但一般认为急性（即时）CIV主要是由于胃肠道内5-羟色胺（5-HT）的释放，而延迟期发生在脑干P物质（SP）释放之后。目前这项研究的目的是在最不泼辣的呕吐模型中检验这一理论。因此，我们首先研究了顺铂在最小鼩中即时和延迟呕吐效应的时间发展，随后确定了与CIV相关的中枢和外周位点主要呕吐神经递质周转量的伴随变化。顺铂（0、5、10和20 mg/kg， ig）引起剂量和时间依赖性呕吐效应。10 mg/kg剂量的顺铂在治疗后2-3 h和33 h产生了两个阶段的呕吐，相应的峰值平均频率出现在治疗后2-3 h和33 h， 5 mg/kg剂量的顺铂在任何一个阶段都没有引起明显的呕吐，而20 mg/kg剂量的顺铂在治疗前两个阶段都引起了明显的呕吐，但毒性限制了整个47小时的观察。顺铂（10 mg/kg, i.p）诱导的峰值即刻期和延迟期与鼩鼱脑干和空肠中5-羟色胺、多巴胺和SP的周转量同时增加有关。在这两个阶段所讨论的增加似乎是部位特异性的，因为神经递质释放在鼩鼱额叶皮层或十二指肠中没有持续改变，尽管偶尔会发生增加或减少。我们的研究结果表明，最小鼩鼱似乎是CIV两个阶段的敏感和快速呕吐模型，两个呕吐阶段都与脑干和空肠中所有被提到的神经递质释放的特定增加有关。因此，普遍接受的神经递质教条需要更新，因为最近更多的人类神经化学研究以及其他临床发现支持目前在最小鼩鼱中获得的基本结果。(C) 2008 Elsevier B.V.版权所有
Although the neuro transmitter basis of chemotherapy-induced vomiting (CIV) is thought to be multifactorial, it is generally accepted that acute (immediate) CIV is mainly due to the release of serotonin (5-HT) within the gastrointestinal tract, while the delayed phase occurs following substance P (SP) release in the brainstem. The aim of the current study was to test this dogma in the least shrew model of vomiting. Thus, we initially investigated the temporal development of cisplatin's immediate and delayed emetic effects in the least shrew and subsequently determined the concomitant changes in the turnover of major emetic neurotransmitters both in the central and peripheral loci associated with CIV. Cisplatin (0, 5, 10 and 20 mg/kg, i.p.) caused dose- and time-dependent emetic effects. A 10 mg/kg dose of cisplatin produced both phases of emesis with corresponding peak mean frequencies occurring at 2-3 and 33 h post-treatment, at 5 mg/kg it failed to cause significant emesis in either phase, while its 20 mg/kg dose induced both phases earlier but toxicity restricted the full 47 hour observation. Cisplatin (10 mg/kg, i.p.)-induced peak immediate and delayed phases were associated with concomitant increases in the turnover of 5-HT, dopamine and SP in both the shrew brainstem and jejunum. The discussed increases during both phases appear to be site specific since neurotransmitter release was not persistently altered in the shrew frontal cortex or duodenum, although occasionally increases or decreases did occur. Our findings suggest that the least shrew appears to be a sensitive and rapid emesis model for both phases of CIV, and both emetic phases are associated with specific increases in the release of all of the cited neurotransmitters in both the brainstem and jejunum. Thus, the generally accepted neurotransmitter dogma needs to be updated since more recent neurochemical studies in humans as well as other clinical findings support the current basic results obtained in the least shrew. (C) 2008 Elsevier B.V. All rights reserved.