Department of Maternal and Child Health, School of Public Health, Sun Yat-Sen University, 74 Zhongshan Road 2, Guangzhou, 510080, China.
Behav Brain Res. 2011 Mar 17;218(1):184-9. doi: 10.1016/j.bbr.2010.11.049. Epub 2010 Dec 2.
The nucleus accumbens (NAc) is one of the important brain regions for the acquisition of morphine-induced conditioned place preference (CPP), which is a valuable paradigm for detecting the rewarding effects of drugs. However, the underlying molecular mechanisms remain largely unknown. In the present study, we investigated the role of p38 and nuclear factor kappa B (NF-κB) in the NAc in the acquisition of morphine-induced CPP. The results showed that repeated morphine treatment induced the acquisition of CPP and increased the phosphorylation of p38, IκB-α and NF-κB p65 in the NAc. Microinjection of p38 inhibitor SB203580 into the NAc prior to the application of morphine prevented the acquisition of CPP and inhibited the activation of p38, IκB-α and NF-κB p65. Furthermore, pre-infusion of pyrrolidine dithiocarbamate (PDTC), a selective NF-κB inhibitor, into the NAc blocked the CPP but also the phosphorylation of NF-κB p65 induced by morphine. It is concluded that the activation of p38/NF-κB p65 signaling pathway in the NAc plays a critical role in the morphine CPP.
伏隔核（NAc）是获得吗啡诱导的条件性位置偏爱（CPP）的重要脑区之一，这是检测药物奖赏效应的一个有价值的范式。然而，其潜在的分子机制在很大程度上仍不清楚。在本研究中，我们研究了 NAc 中 p38 和核因子 kappa B（NF-κB）在吗啡诱导 CPP 获得中的作用。结果表明，重复给予吗啡处理可诱导 CPP 的获得，并增加 NAc 中 p38、IκB-α 和 NF-κB p65 的磷酸化。在给予吗啡之前，将 p38 抑制剂 SB203580 微注射到 NAc 中，可防止 CPP 的获得，并抑制 p38、IκB-α 和 NF-κB p65 的激活。此外，预先将选择性 NF-κB 抑制剂吡咯烷二硫代氨基甲酸盐（PDTC）注入 NAc 中，可阻断 CPP，但也可阻断吗啡诱导的 NF-κB p65 磷酸化。综上所述，NAc 中 p38/NF-κB p65 信号通路的激活在吗啡 CPP 中起着关键作用。
