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.