Yohimbine prevents morphine-induced changes of glial fibrillary acidic protein in brainstem and α2-adrenoceptor gene expression in hippocampus
Yohimbine prevents morphine-induced changes of glial fibrillary acidic protein in brainstem and α2-adrenoceptor gene expression in hippocampus
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DOI：
10.1016/j.neulet.2006.11.002
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发表时间：
2007-01-29
影响因子：
2.5
通讯作者：
Alguacil, Luis F.
中科院分区：
文献类型：
--
作者：
Alonso, Elba;Garrido, Elisa;Alguacil, Luis F.
已知α(2)-肾上腺素受体拮抗剂育亨宾可对抗阿片类药物的多种药理作用，但其后果和所涉及的机制仍有待明确确定。在本研究中，我们检查了育亨宾对吗啡诱导的大鼠大脑区域中关键蛋白（胶质纤维酸性蛋白，GFAP）和基因（α（2）-肾上腺素受体）表达改变的影响，这些区域已知与阿片类药物依赖、成瘾和个体对药物滥用的脆弱性相关。在育亨宾存在或不存在的情况下用吗啡治疗大鼠。通过蓝斑 (LC) 和孤束核 (NST)（两个重要的去甲肾上腺素能核）的免疫组织化学染色研究了治疗对 GFAP 表达的影响。此外，通过海马体中的实时 RT-PCR 确定药物对 α(2)-肾上腺素受体基因表达的影响，海马体是接收来自脑干的去甲肾上腺素能输入的大脑区域。吗啡给药增加了 LC 和 NST 中 GFAP 的表达，正如之前在其他大脑区域中报道的那样。育亨宾被发现可以有效防止吗啡诱导的 GFAP 上调。慢性（而非急性）吗啡下调海马中α(2A)-和α(2C)-肾上腺素受体的mRNA水平，同时增加α(2B)-肾上腺素受体基因的表达。同样，育亨宾能够防止吗啡诱导的三种 α(2)-肾上腺素受体基因表达水平的变化。这些结果与育亨宾已证实的减少阿片类药物依赖和成瘾相关，并表明该药物可能干扰中枢去甲肾上腺素能通路中慢性吗啡诱导的神经可塑性。 (c) 2006 Elsevier Ireland Ltd. 保留所有权利。
The alpha(2)-adrenoceptor antagonist yohimbine is known to oppose to several pharmacological effects of opioid drugs, but the consequences and the mechanisms involved remain to be clearly established. In the present study we have checked the effects of yohimbine on morphine-induced alterations of the expression of key proteins (glial fibrillary acidic protein, GFAP) and genes (alpha(2)-adrenoceptors) in rat brain areas known to be relevant in opioid dependence, addiction and individual vulnerability to drug abuse. Rats were treated with morphine in the presence or absence of yohimbine. The effects of the treatments on GFAP expression were studied by immunohistochemical staining in Locus Coeruleus (LC) and Nucleus of the Solitary Tract (NST), two important noradrenergic nuclei. In addition, drug effects on alpha(2)-adrenoceptor gene expression were determined by real time RT-PCR in the hippocampus, a brain area that receives noradrenergic input from the brainstem. Morphine administration increased GFAP expression both in LC and NST as it was previously reported in other brain areas. Yohimbine was found to efficiently prevent morphine-induced GFAP upregulation. Chronic (but not acute) morphine downregulated mRNA levels of alpha(2A)- and alpha(2C)-adrenoceptors in the hippocampus, while simultaneously increased the expression of the alpha(2B)-adrenoceptor gene. Again, yohimbine was able to prevent morphine-induced changes in the levels of expression of the three alpha(2)-adrenoceptor genes. These results correlate the well-established reduction of opioid dependence and addiction by yohimbine and suggest that this drug could interfere with the neural plasticity induced by chronic morphine in central noradrenergic pathways. (c) 2006 Elsevier Ireland Ltd. All rights reserved.