Disruption of morphine-conditioned place preference by a delta2-opioid receptor antagonist: study of mu-opioid and delta-opioid receptor expression at the synapse.
Disruption of morphine-conditioned place preference by a delta2-opioid receptor antagonist: study of mu-opioid and delta-opioid receptor expression at the synapse.
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DOI：
10.1111/j.1460-9568.2010.07314.x
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发表时间：
2010-08
期刊：
影响因子：
--
通讯作者：
Morón JA
中科院分区：
文献类型：
--
作者：
Billa SK;Xia Y;Morón JA
吗啡的成瘾性限制了它的临床应用。滥用阿片类药物和环境之间的习得性联系是通过巴甫洛夫条件反射过程产生的。破坏阿片和环境线索之间的习得性联系可能是预防吗啡依赖的一种治疗方法。虽然δ-阿片受体在调节吗啡的奖励特性中的作用已经被证明，在这项研究中，我们进一步表征δ-阿片受体在吗啡诱导的条件反应中的作用，通过检查选择性δ-2-阿片受体拮抗剂（naltriben）的作用，使用大鼠条件性位置偏爱范例。此外，我们使用亚细胞分离技术来分析海马中的μ-和δ-阿片受体的突触定位，以检查可能是这种吗啡诱导的条件性行为的分子机制。我们的数据表明，在吗啡之前给予1 mg/kg纳曲苯（但不是0.1 mg/kg）能够阻断吗啡诱导的条件性位置偏爱。有趣的是，这种纳曲苯诱导的吗啡条件性位置偏爱的破坏与突触后密度的δ-阿片受体二聚体表达的显著增加有关。此外，我们还观察到吗啡条件性位置偏爱与总匀浆中μ阿片受体表达的增加有关。总之，这些结果表明，δ-阿片受体的表达和其突触定位的调制可能构成一个可行的治疗方法来破坏吗啡诱导的条件反应。
The addictive properties of morphine limit its clinical use. Learned associations that develop between the abused opiate and the environment in which it is consumed are engendered through Pavlovian conditioning processes. Disruption of the learned associations between the opiate and environmental cues may be a therapeutic approach to prevent morphine dependence. Although a role for the delta-opioid receptor in the regulation of the rewarding properties of morphine has already been shown, in this study we further characterize the role of the delta-opioid receptor in morphine-induced conditioned responses by examining the effect of a selective delta-2-opioid receptor antagonist (naltriben) using a conditioned place preference paradigm in rats. Additionally, we used a subcellular fractionation technique to analyze the synaptic localization of mu- and delta-opioid receptors in the hippocampus in order to examine the molecular mechanisms that may underlie this morphine-induced conditioned behavior. Our data show that the administration of 1 mg/kg naltriben (but not 0.1 mg/kg) prior to morphine was able to block morphine-induced conditioned place preference. Interestingly, this naltriben-induced disruption of morphine conditioned place preference was associated with a significant increase in the expression of the delta-opioid receptor dimer at the postsynaptic density. In addition, we also observed that morphine conditioned place preference was associated with an increase in the expression of the mu-opoid receptor in the total homogenate. Overall, these results suggest that the modulation of the delta-opioid receptor expression and its synaptic localization may constitute a viable therapeutic approach to disrupt morphine-induced conditioned responses.
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