Yohimbine prevents morphine-induced changes of glial fibrillary acidic protein in brainstem and α2-adrenoceptor gene expression in hippocampus

Lab. Pharmacology and Toxicology, Universidad San Pablo CEU, 28668 Boadilla del Monte, Madrid, Spain.
Neuroscience Letters (Impact Factor: 2.03). 02/2007; 412(2):163-7. DOI: 10.1016/j.neulet.2006.11.002
Source: PubMed


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.

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    • "Ina is another intermediate filament protein expressed only in neurons, and can cause CNS plasticity by facilitating axonal neurite elongation [37]. These data are consistent with previous reports showing that morphine administration impact GFAP expression in certain brain areas [38], and support previously published evidence showing that morphine tolerance is actually a disorder of neuroplasticity [39], [40]. "
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    Full-text · Article · Jan 2014 · PLoS ONE
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    • "Importantly , this proinflammatory phenotype induced by morphine has been observed to be brain region specific and in some regions glial cell type specific. For example, astrocytes are activated following chronic morphine administration in the locus ceruleus and nucleus of the solitary tract (Alonso et al., 2007), lateral septal nucleus (Lazriev et al., 2001), ventral tegmental area, nucleus accumbens, dentate gyrus, Cornu ammonis of the hippocampus, dorsal periaqueductal gray, medial prefrontal cortex, ventral periaqueductal gray, caudate putamen, rostral ventromedial medulla and trigeminal nucleus, but not in the dorsal raphe nucleus, caudate nucleus and the substantia nigra (Lazriev et al., 2001; Hutchinson et al., 2009a). In contrast, microglia are only activated by chronic systemic morphine in the ventral tegmental area, dentate gyrus, dorsal periaqueductal gray, ventral periaqueductal gray, caudate putamen, rostral ventromedial medulla and the trigeminal nucleus, but not in the nucleus accumbens, C. ammonis of the hippocampus, substantia nigra, medial prefrontal cortex and dorsal raphe nucleus (Hutchinson et al., 2009a). "
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    • "NM_031012). GAPDH was used as a positive control, and the following primers were adopted: GAPDH sense — 5′-TTCAACGGCACAGTCAAGGC-3′, GAPDH anti-sense — 5′-CACCAGCATCACCCCATTTG-3′ [28] (GenBank access no: NM_017008). "
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