Research reportInvolvement of p38/NF-κB signaling pathway in the nucleus accumbens in the rewarding effects of morphine in rats

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.

Research highlights▶ p38 activation plays a critical role in the acquisition of morphine-induced CPP. ▶ The phosphorylation of NF-κB p65 in the NAc is necessary for morphine CPP. ▶ Our study provides novel evidence that p38 participates in the morphine CPP by activating NF-κB p65.