1. ¹Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Technical University Munich, Germany
2. ²Max-Planck-Institute of Psychiatry, Molecular Neurogenetics, Munich, Germany
3. ³Department of Psychology, University of Vermont, Burlington, VT, USA

Correspondence: Dr SM Hölter, Institute of Developmental Genetics, Helmholtz Zentrum München-German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, Neuherberg/Munich, Bayern 85764, Germany, Tel: +49 89 3187 3674, Fax: +49 89 3187 3099, E-mail: hoelter@helmholtz-muenchen.de; Dr W Wurst, Tel: +49 89 3187 4110, Fax: +49 89 3187 3099, E-mail: wurst@helmholtz-muenchen.de

Received 14 October 2007; Revised 30 January 2008; Accepted 6 March 2008; Published online 23 April 2008.

Abstract

There is considerable interest in examining the genes that may contribute to anxiety. We examined the function of ERK/MAPK in the acquisition of conditioned fear, as measured by fear-potentiated startle (FPS) in mice as a model for anticipatory anxiety in humans. We characterized the following for the first time in the mouse: (1) the expression of the ERK/MAPK signaling pathway components at the protein level in the lateral amygdala (LA); (2) the time course of activation of phospho-activated MAPK in the LA after fear conditioning; (3) if pharmacological inhibition of pMAPK could modulate the acquisition of FPS; (4) the cell-type specificity of pMAPK in the LA after fear conditioning. Using western blot and immunohistochemistry techniques and injecting the MEK inhibitor U0126 in the LA, we showed the following: (1) both MEK1/MEK2 and ERK1/ERK2 were co-expressed in the LA of the adult mouse brain; (2) there is a peak of pMAPK at 60 min after fear conditioning; (3) the ERK/MAPK signaling pathway activation is essential for the acquisition of an FPS response; (4) at 60 min, the pMAPK are exclusively neuronal and not glial. These results emphasize the importance of this signaling pathway in the acquisition of conditioned fear in the mouse. Given the widely held view that conditioned fear models the essential aspects of anxiety disorders, the results confirm the ERK/MAPK signaling pathway as a molecular target for the treatment of anxiety disorders in the clinic.