Cue-elicited drug craving represses ERK activation in mice prefrontal association cortex

Morphine addiction is characterized by compulsive drug-taking behavior and high rates of relapse that reflect reward-controlled learning, consolidation and reconsolidation of drug cues. Extracellular signal-regulated protein kinase (ERK) is one of the cellular molecules that have been highly implicated in the synaptic plasticity processes of learning and memory in cocaine addiction. However, the roles of ERK in the morphine-paired conditioned place preference (CPP) are not clear. In the present study, we found that compared to the morphine-unpaired and saline-paired and saline-unpaired groups, morphine-paired mice showed depressed ERK2 activity in the Frontal Association Cortex (FrA), whereas ERK1 activity was not changed in the same region. In the Accumbens Nucleus (Acb) and Caudate Putamen (CPu) that are associated with cocaine addiction, the activities of ERK1 and ERK2 among four groups showed no difference. These results suggest that the FrA plays an important role in morphine craving and that ERK2 is involved in eliciting the environment-related morphine craving, which is totally different from those induced by morphine itself. (c) 2008 Elsevier Ireland Ltd. All rights reserved

吗啡成瘾的特征是强迫性的用药行为以及高复发率，这反映了受奖赏控制的学习、药物线索的巩固和再巩固。细胞外信号调节蛋白激酶（ERK）是一种在可卡因成瘾的学习和记忆的突触可塑性过程中密切相关的细胞分子。然而，ERK在吗啡配对的条件性位置偏爱（CPP）中的作用尚不清楚。在本研究中，我们发现与吗啡非配对组、盐水配对组和盐水非配对组相比，吗啡配对组小鼠的额叶联合皮质（FrA）中ERK2活性降低，而同一区域的ERK1活性没有变化。在与可卡因成瘾相关的伏隔核（Acb）和尾状壳核（CPu）中，四组之间的ERK1和ERK2活性没有差异。这些结果表明，额叶联合皮质在吗啡渴求中起重要作用，并且ERK2参与引发与环境相关的吗啡渴求，这与吗啡本身所诱导的情况完全不同。（c）2008爱思唯尔爱尔兰有限公司。保留所有权利