Prefrontal infusion of PD098059 immediately after fear extinction training blocks extinction-associated prefrontal synaptic plasticity and decreases prefrontal ERK2 phosphorylation

Authors

  • Sandrine Hugues,

    1. Laboratoire de Neurobiologie et Psychopathologie, Faculté des Sciences, Université de Nice-Sophia Antipolis, Nice, France
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  • Aline Chessel,

    1. Laboratoire de Neurobiologie et Psychopathologie, Faculté des Sciences, Université de Nice-Sophia Antipolis, Nice, France
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  • Isabelle Lena,

    1. Laboratoire de Neurobiologie et Psychopathologie, Faculté des Sciences, Université de Nice-Sophia Antipolis, Nice, France
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  • Robert Marsault,

    1. Transporteurs en Imagerie et Radiotherapie en Oncologie, Faculté de Médecine, Université de Nice-Sophia Antipolis, Nice, France
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  • Rene Garcia

    Corresponding author
    1. Laboratoire de Neurobiologie et Psychopathologie, Faculté des Sciences, Université de Nice-Sophia Antipolis, Nice, France
    • Laboratoire de Neurobiologie et Psychopathologie, Université de Nice-Sophia Antipolis, Parc Valrose, 06108 Nice, France
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Abstract

A previous study has demonstrated that disruption of fear extinction-induced long-term potentiation (LTP) in the medial prefrontal cortex (mPFC) is associated with the return of fear responding. Given that immediate posttraining infusion of PD098059, an inhibitor of extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) cascade, into the mPFC also promotes recovery of fear, we investigated whether impairment of mPFC ERK/MAPK cascade also interferes with development of extinction-related LTP in the mPFC in rats. In Experiment 1, extinction training consisting of repetitive presentations of a tone previously associated with eyelid-shock application induced LTP-like changes at hippocampal inputs to the mPFC that were evident for ˜2 h following fear extinction. Infusion of PD098059 into the mPFC immediately after extinction training abolished training-related prefrontal LTP and impaired retention of extinction memory tested on the following day. In Experiment 2, immunoblotting assays revealed that posttraining infusion of PD098059 into the mPFC produced a significant reduction of mPFC ERK2. These data, along with previous findings, suggest that low levels of ERK2 phosphorylation in the mPFC may interfere with mechanisms of retention of extinction training. The involvement of mPFC LTP in fear extinction is discussed. Synapse 60:280–287, 2006. © 2006 Wiley-Liss, Inc.

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