Abstract
A major goal of research on drug addiction is to develop the effective treatments to deal with the long‐term behavioral disorders especially reinstatement induced by the addictive drugs such as opiates, cocaine, and cannabinoid. The molecular mechanisms underlying these substance‐related disorders remain unclear so far. Here we used the model of morphine‐induced conditioned place preference (CPP) in rats to mimic the progress of drug‐taking, withdrawal and relapse in human. The tissue of ventral tegmental area (VTA), one of the most important brain structures associated with abused drug‐related disorders, was taken and two‐dimensional electrophoresis (2‐DE) was performed to analyze and compare the changes of protein expression patterns during the different stages of morphine‐induced CPP. First, we found that there were 80 proteins identified to be changed in the process of morphine‐induced CPP. Furthermore, as the mitogen‐activated protein kinase kinase 1 (MAPKK1) was increased significantly in the stages of establishment and reinstatement, we confirmed the change of activated extracellular signal‐regulated kinase (ERK) by Western blotting in VTA tissue and cultured cell. The results demonstrated that the activated MEK‐ERK pathway by chronic morphine treatment in VTA was involved in morphine‐induced reinstatement. Moreover, inhibition of MEK‐ERK pathway by infusion the MEK inhibitor U0126 in VTA blocked the establishment of morphine‐induced CPP. The present study found significant changes in a group of protein expressions in VTA during morphine‐induced CPP and further confirmed the role of MEK‐ERK cell signaling pathway of VTA in morphine addiction. © 2010 Wiley‐Liss, Inc.