Enhanced morphine withdrawal and μ-opioid receptor G-protein coupling in A2A adenosine receptor knockout ti ice
Enhanced morphine withdrawal and μ-opioid receptor G-protein coupling in A2A adenosine receptor knockout ti ice
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DOI：
10.1046/j.1471-4159.2003.02214.x
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发表时间：
2004-02-01
影响因子：
4.7
通讯作者：
Kitchen, I
中科院分区：
文献类型：
--
作者：
Bailey, A;Davis, L;Kitchen, I
许多证据支持A(2A)腺苷受体在吗啡戒断的表达中起重要作用的假设，并认为多巴胺能系统也可能参与其中。我们评估了野生型和A(2A)受体基因敲除小鼠的吗啡戒断症状，并显示出一些戒断迹象在基因敲除小鼠中显著增强。此外，还对戒断野生型和基因敲除小鼠的脑切片进行了G-阿片受体和多巴胺D-2受体放射自显影，以及Mu-阿片受体刺激的鸟苷5‘-[[S-35]硫代]-三磷酸鸟苷放射自显影。在所分析的任何脑区中，D-2和Mu-阿片受体结合没有明显变化。然而，Mu受体刺激的[S-35]GTP-GammaS结合水平在戒断基因敲除小鼠伏隔核中观察到显著增加。这些数据表明，A(2A)受体在阿片类药物戒断中起作用，与功能性受体激活有关。
Much evidence supports the hypothesis that A(2A) adenosine receptors play an important role in the expression of morphine withdrawal and that the dopaminergic system might also be involved. We have evaluated morphine withdrawal signs in wild-type and A(2A) receptor knockout mice and shown a significant enhancement in some withdrawal signs in the knockout mice. In addition, g-opioid and dopamine D-2 receptor auto radiography, as well as mu-opioid receptor-stimulated guanylyl 5'-[gamma-[S-35]thio]-triphosphate ([S-35]GTPgammaS) autoradiography was carried out in brain sections of withdrawn wild-type and knockout mice. No significant changes in D-2 and mu-opioid receptor binding were observed in any of the brain regions analysed. However, a significant increase in the level of mu receptor-stimulated [S-35]GTPgammaS binding was observed in the nucleus accumbens of withdrawn knockout mice. These data indicate that the A(2A) receptor plays a role in opioid withdrawal related to functional receptor activation.