Huang Mengbing, Kong Lingpin, Yang Lihua, Li Xiang, Zhou Xiaoshuang, Li Ye, Bai Jie
Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming 650500, China; Medical Faculty, Kunming University of Science and Technology, Kunming 650500, China.
Medical Faculty, Kunming University of Science and Technology, Kunming 650500, China.
Behav Brain Res. 2018 Jan 30;337:280-286. doi: 10.1016/j.bbr.2017.07.047. Epub 2017 Aug 4.
Methamphetamine (METH) is a highly addictive drug of abuse which induces behavioral sensitization and rewarding effects. Thioredoxin-1 (Trx-1) is a redox protein and plays roles in regulating activity of transcription factor, such as cAMP responsive element-binding protein (CREB), AP-1, p53, is emerging as an important modulator of neuronal function. It has been reported that Trx-1 is involved in morphine dependence. In this study, we examined the rewarding effect after METH administration by conditioned place preference (CPP) of mice, and detected the levels of dopamine and the activity of cAMP responsive element-binding protein (CREB), the expressions of ΔFosB and cyclin-dependent kinase 5 (CDK5) in the ventral tegmental area (VTA) and nucleus accumbens (NAc) in mice. Our results showed that the expression of METH-CPP was occluded in Trx-1 overexpression transgenic (TG) mice. The increase of dopamine level induced by METH was not further higher in Trx-1 TG mice. METH decreased the expression of Trx-1 which was restored in TG mice. The activity of CREB and the expressions of ΔFosB and CDK5 were increased by METH in wile-type mice, which were not further increased in TG mice. These results suggest that overexpression of Trx-1 may occlude the CPP induced by METH through regulating the activity of CREB and the expression of ΔFosB.
甲基苯丙胺（METH）是一种极易成瘾的滥用药物，会诱发行为敏化和奖赏效应。硫氧还蛋白-1（Trx-1）是一种氧化还原蛋白，在调节转录因子活性（如环磷酸腺苷反应元件结合蛋白（CREB）、活化蛋白-1（AP-1）、p53）中发挥作用，正成为神经元功能的重要调节因子。据报道，Trx-1参与吗啡依赖。在本研究中，我们通过小鼠条件性位置偏爱（CPP）实验检测了给予METH后的奖赏效应，并检测了小鼠腹侧被盖区（VTA）和伏隔核（NAc）中多巴胺水平、环磷酸腺苷反应元件结合蛋白（CREB）的活性、ΔFosB和细胞周期蛋白依赖性激酶5（CDK5）的表达。我们的结果表明，在Trx-1过表达转基因（TG）小鼠中，METH-CPP的表达被阻断。Trx-1 TG小鼠中由METH诱导的多巴胺水平升高并未进一步增加。METH降低了Trx-1的表达，而在TG小鼠中该表达得以恢复。在野生型小鼠中，METH增加了CREB的活性以及ΔFosB和CDK5的表达，而在TG小鼠中这些并未进一步增加。这些结果表明，Trx-1的过表达可能通过调节CREB的活性和ΔFosB的表达来阻断由METH诱导的CPP。
