Department of Histology and Embryology, Guizhou Medical University, Guiyang, Guizhou, China (mainland).
Med Sci Monit. 2018 Jun 5;24:3789-3803. doi: 10.12659/MSM.910550.
BACKGROUND Synaptic plasticity plays an important role in the process of addiction. This study investigated the relationship between synaptic plasticity and changes in addictive behavior and examined the expression of synaptic plasticity-associated proteins and genes in the nucleus accumbens (NAc) region in different rat models. MATERIAL AND METHODS Heroin addiction, SIRT1-overexpression, and SIRT1-silenced rat models were established. Polymerase chain reaction gene chip technology, immunohistochemistry, Western blotting, and transmission electron microscopy were used to detect changes in synaptic plasticity-related gene and protein expression, and changes in the ultrastructure of synapses, in the NAc. RESULTS Naloxone withdrawal symptoms appeared in the SIRT1-overexpression group. In the SIRT1-silenced group the symptoms were reduced. Immunohistochemistry and Western blotting results showed that FOXO1 expression decreased in the heroin addiction (HA) group but increased in the SIRT1-silenced group (p<0.05). The expression of Cdk5, Nf-κB, PSD95, and Syn was enhanced in the HA group (p<0.05) and further increased in the SIRT1-overexpression group but were reduced in the SIRT1-silenced group (p<0.05). The number of synapses increased in the HA group (p<0.05) along with mitochondrial swelling in the presynaptic membrane and obscuring of the synaptic cleft. CONCLUSIONS SIRT1 and other synaptic plasticity-related genes in NAc are involved in the regulation of heroin addiction. SIRT1 overexpression can increase behavioral sensitization in the NAc of rats, and SIRT1 silencing might ease withdrawal symptoms and reduce conditioned place preferences.
突触可塑性在成瘾过程中起着重要作用。本研究探讨了突触可塑性与成瘾行为变化的关系，并研究了不同大鼠模型伏隔核（NAc）区域中与突触可塑性相关的蛋白和基因的表达。
建立了海洛因成瘾、SIRT1 过表达和 SIRT1 沉默大鼠模型。采用聚合酶链反应基因芯片技术、免疫组织化学、Western blot 和透射电镜检测 NAc 中与突触可塑性相关的基因和蛋白表达变化以及突触超微结构变化。
SIRT1 过表达组出现纳洛酮戒断症状，SIRT1 沉默组症状减轻。免疫组织化学和 Western blot 结果显示，FOXO1 在海洛因成瘾（HA）组表达减少，但在 SIRT1 沉默组表达增加（p<0.05）。Cdk5、Nf-κB、PSD95 和 Syn 在 HA 组表达增强（p<0.05），在 SIRT1 过表达组进一步增强，但在 SIRT1 沉默组减少（p<0.05）。HA 组突触数量增加（p<0.05），同时突触前膜线粒体肿胀，突触间隙模糊。
NAc 中的 SIRT1 和其他与突触可塑性相关的基因参与了海洛因成瘾的调节。SIRT1 过表达可增加大鼠 NAc 中的行为敏化，SIRT1 沉默可能缓解戒断症状并减少条件性位置偏爱。
