Yohimbine prevents morphine-induced changes of glial fibrillary acidic protein in brainstem and α<sub>2sub>-adrenoceptor gene expression in hippocampus
- 作者：Elba Alonso ; Elisa Garrido ; Carmen Dí ; ez-Ferná ; ndez ; Carmen Pé ; rez-Garcí ; a ; Gonzalo Herradó ; n ; Laura Ezquerra ; Thomas F. Deuel ; Luis F. Alguacil
- 关键词：Morphine ; Yohimbine ; Glial fibrillary acidic protein ; α ; <sub>2sub>-Adrenoceptor ; Locus coeruleus ; Hippocampus
- 刊名：Neuroscience Letters
- 出版年：2007
- 期刊代码：52_03043940
- 类别：neu
- 出版时间：29 January 2007
- 卷：412
- 期：2
- 页码：163-167
- 文件大小：372 K
摘要
The α<sub>2sub>-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 (α<sub>2sub>-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 α<sub>2sub>-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 α<sub>2Asub>- and α<sub>2Csub>-adrenoceptors in the hippocampus, while simultaneously increased the expression of the α<sub>2Bsub>-adrenoceptor gene. Again, yohimbine was able to prevent morphine-induced changes in the levels of expression of the three α<sub>2sub>-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.