Acute systemic fibroblast growth factor-2 enhances long-term extinction of fear and reduces reinstatement in rats

Neuropsychopharmacology. 2009 Jun;34(7):1875-82. doi: 10.1038/npp.2009.14. Epub 2009 Feb 18.


Despite having made substantial advances in the treatment of anxiety disorders over the past few decades it appears that we have now reached a 'therapeutic impasse'. Further clinical progress requires a greater understanding of the neural mechanisms underlying fear inhibition. In this study, we examined, for the first time, the effects of fibroblast growth factor-2 (FGF2), a mitogen involved in the molecular cascade of memory, on extinction and relapse in rats. In all experiments, rats were first trained to fear a white noise-conditioned stimulus, and then had this learned fear extinguished the following day. Extinction is the process underlying exposure-based therapy in humans. Experiments 1 and 2 demonstrated that FGF2 facilitated the loss of learned fear (ie, extinction) when given either prior to or immediately after extinction but not when given 4 h after extinction. This suggests that FGF2 must be present during the consolidation of the extinction memory to have an effect. Experiment 3 further supported this interpretation by showing that short-term extinction must occur for FGF2 to facilitate long-term extinction, suggesting that FGF2 is facilitating the translation of memory from short-term to long-term storage. In experiment 4 rats given FGF2 immediately after extinction exhibited less shock-induced reinstatement, which is a model preparation of relapse, than did vehicle-treated rats. Together, these experiments demonstrate that FGF2 facilitates extinction and attenuates relapse. Thus, FGF2 may be a novel pharmacological adjunct to exposure therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Conditioning, Classical / drug effects*
  • Conditioning, Classical / physiology
  • Extinction, Psychological / drug effects*
  • Fear / drug effects*
  • Fibroblast Growth Factor 2 / pharmacology*
  • Freezing Reaction, Cataleptic / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Reinforcement, Psychology*
  • Time Factors


  • Fibroblast Growth Factor 2