Role of MEK-ERK pathway in morphine-induced conditioned place preference in ventral tegmental area of rats.
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.
Lin
XiaoJing
X
The National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University, Beijing, China.
Wang
QingSong
Q
Ji
Jianguo
J
Yu
Long-Chuan
LC
D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048369:MAP Kinase Kinase 1 / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000378:metabolism* / Q000503:physiopathology; D009294:Narcotics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism*
D004791:Enzyme Inhibitors; D009294:Narcotics; D009020:Morphine; D048052:Mitogen-Activated Protein Kinase 3; D048369:MAP Kinase Kinase 1