A novel molecule "Shati" is involved in methamphetamine-induced hyperlocomotion, sensitization, and conditioned place preference
A novel molecule "Shati" is involved in methamphetamine-induced hyperlocomotion, sensitization, and conditioned place preference
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DOI：
10.1523/jneurosci.1575-07.2007
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发表时间：
2007-07-11
影响因子：
5.3
通讯作者：
Nabeshima, Toshitaka
中科院分区：
文献类型：
--
作者：
Niwa, Minae;Nitta, Atsumi;Nabeshima, Toshitaka
吸毒给社会带来了巨大的负担，它对犯罪率和医疗保健造成了影响。反复接触滥用药物会导致特定神经元群体的细胞适应，最终可能导致成瘾状态。在本研究中，我们用聚合酶链式反应-选择性互补DNA消减方法从甲基苯丙胺处理的小鼠的伏隔核(NAC)中鉴定出一种新的分子“沙提”。此外，我们还研究了Shati是否参与了冰毒诱导的多动、敏化和条件性位置偏爱(CPP)。METH通过多巴胺(DA)受体剂量依赖性地诱导Shati基因表达。我们制备了针对Shati的抗体，并使用它们发现Shati在小鼠大脑的神经细胞中表达。用显著抑制Shati mRNA表达的Shati反义寡核苷酸(Shati-AS)治疗，可增强急性冰毒反应、冰毒诱导的行为敏化和CPP。阻断Shati-AS可增强冰毒引起的NAc多巴胺溢出增加和冰毒引起的突触小体和囊泡多巴胺摄取减少。这些结果表明，一个新的分子Shati参与了冰毒诱导的多动、敏化和CPP的发展。Shati在冰毒调节的行为改变中的作用可能是通过抑制冰毒引起的NAc多巴胺溢出增加和冰毒引起的中脑DA摄取减少而实现的。
Drug addiction places an enormous burden on society through its repercussions on crime rate and healthcare. Repeated exposure to drugs of abuse causes cellular adaptations in specific neuronal populations that ultimately can lead to a state of addiction. In the present study, we have identified a novel molecule "shati" from the nucleus accumbens (NAc) of mice treated with methamphetamine ( METH) using the PCR-select complementary DNA subtraction method. Moreover, we investigated whether shati is involved in METH-induced hyperlocomotion, sensitization, and conditioned place preference (CPP). METH induced expression of shati mRNA dose dependently via dopamine (DA) receptors. We prepared antibodies against shati and, using them, found shati to be expressed in neuronal cells of the mouse brain. Treatment with the shati antisense oligonucleotide (shati-AS), which significantly inhibited the expression of shati mRNA, enhanced the acute METH response, METH-induced behavioral sensitization, and CPP. Blockage of shati mRNA by shati-AS potentiated the METH-induced increase of DA overflow in the NAc and the METH-induced decrease in synaptosomal and vesicular DA uptake in the midbrain. These results suggest that a novel molecule shati is involved in the development of METH-induced hyperlocomotion, sensitization, and CPP. The functional roles of shati in METH-regulated behavioral alternations are likely to be mediated by its inhibitory effects on the METH-induced increase of DA overflow in the NAc and the METH-induced decrease in DA uptake in the midbrain.