title: Acute systemic fibroblast growth factor-2 enhances long-term extinction of fear and reduces reinstatement in rats.
abstract: 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.
authors.affiliation: School of Psychology, University of New South Wales, Sydney, NSW, Australia. bgraham@psy.unsw.edu.au
authors.forename: Bronwyn M
authors.initials: BM
authors.lastname: Graham
authors.forename: Rick
authors.initials: R
authors.lastname: Richardson
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003214:Conditioning, Classical / Q000187:drug effects* / Q000502:physiology; D005108:Extinction, Psychological / Q000187:drug effects*; D005239:Fear / Q000187:drug effects*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D013997:Time Factors
chemical_list: D016222:Fibroblast Growth Factor 2