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

Synapse. 2006 Sep 15;60(4):280-7. doi: 10.1002/syn.20291.


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 approximately 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Electrodes, Implanted
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacology*
  • Extinction, Psychological / drug effects*
  • Flavonoids / administration & dosage
  • Flavonoids / pharmacology*
  • Injections
  • MAP Kinase Kinase 2 / antagonists & inhibitors*
  • MAP Kinase Kinase 2 / metabolism*
  • Male
  • Memory / drug effects
  • Neuronal Plasticity / drug effects*
  • Phosphorylation
  • Prefrontal Cortex / physiology*
  • Rats
  • Rats, Wistar
  • Synapses / drug effects*


  • Enzyme Inhibitors
  • Flavonoids
  • MAP Kinase Kinase 2
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one