Role of extracellular signal-regulated kinase signal transduction pathway in anxiety

Extracellular signal-regulated kinase (ERK) signal transduction pathway is widely implicated in multiple physiological processes. However, it remains to be determined whether ERK pathway plays roles in anxiety. Here we investigated the changes of phosphorylated ERK1/2 (pERK1/2) and c-Fos expression by immunostaining in the medial prefrontal cortex (mPFC) of anxious rats. The results indicated that the levels of pERK and c-Fos were significantly increased during anxiety. Inhibition of ERK phosphorylation blocked the anxiety-induced c-Fos expression. In the animal behavioral tests, the PD98059-treated anxious rats had a significant increase in the numbers of the open-arm entries, the time spent in the open-arms and the numbers of head-dipping in EPM test, and increase the inner locomotion in the open field test compared with the anxious rats. The results suggested that the ERK signal transduction pathway might play an important role in anxiety, and inhibition of the ERK pathway in the mPFC could produce anxiolysis effect. (C) 2008 Elsevier Ltd. All rights reserved.