Involvement of p38/NF-kappaB signaling pathway in the nucleus accumbens in the rewarding effects of morphine in rats.

摘要

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-kappaB) 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, IkappaB-alpha and NF-kappaB 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, IkappaB-alpha and NF-kappaB p65. Furthermore, pre-infusion of pyrrolidine dithiocarbamate (PDTC), a selective NF-kappaB inhibitor, into the NAc blocked the CPP but also the phosphorylation of NF-kappaB p65 induced by morphine. It is concluded that the activation of p38/NF-kappaB p65 signaling pathway in the NAc plays a critical role in the morphine CPP.