Yong Z, Yan L, Gao X, Gong Z, Su R
Beijing Institute of Pharmacology & Toxicology, 27 Taiping Road, Beijing 100850, China.
Beijing Institute of Pharmacology & Toxicology, 27 Taiping Road, Beijing 100850, China.
Neuroscience. 2014 Aug 22;274:53-8. doi: 10.1016/j.neuroscience.2014.05.026. Epub 2014 May 23.
The partial opioid agonist thienorphine is currently in Phase II clinical trials in China as a candidate drug for the treatment of opioid dependence. However, its effect on synaptic plasticity in the NAc (nucleus accumbens) remains unclear. In the present study, we measured structural parameters of the synaptic interface to investigate the effect of thienorphine, morphine or a combination of both on synaptic morphology in the NAc of rats. Expression of synaptophysin was also examined. Ultrastructural observation showed that synaptic alterations were less pronounced after chronic thienorphine administration than after chronic morphine administration. Animals that received thienorphine had thinner postsynaptic densities and shorter active zones in the NAc compared with those in the saline group, but the active zone was larger, and the cleft narrower, than those in the morphine group. Furthermore, synaptophysin expression in the NAc was significantly greater after chronic administration of thienorphine, morphine, or both, than after saline. These results identified interesting differences between thienorphine and morphine in their effects on synaptic structure and synaptophysin expression in the rat NAc. Further study is deserved to investigate thienorphine as a new treatment for opioid dependence.
部分阿片类激动剂噻诺啡目前在中国正处于II期临床试验阶段，作为治疗阿片类药物依赖的候选药物。然而，其对伏隔核（NAc）突触可塑性的影响仍不清楚。在本研究中，我们测量了突触界面的结构参数，以研究噻诺啡、吗啡或两者组合对大鼠NAc突触形态的影响。还检测了突触素的表达。超微结构观察表明，与慢性给予吗啡相比，慢性给予噻诺啡后突触改变不那么明显。与生理盐水组相比，接受噻诺啡的动物在NAc中的突触后致密物更薄，活性区更短，但与吗啡组相比，活性区更大，裂隙更窄。此外，慢性给予噻诺啡、吗啡或两者后，NAc中突触素的表达显著高于生理盐水组。这些结果揭示了噻诺啡和吗啡在对大鼠NAc突触结构和突触素表达的影响方面存在有趣的差异。值得进一步研究将噻诺啡作为阿片类药物依赖的新治疗方法。
