Fibroblast growth factor-2 enhancement of extinction recall depends on the success of within-session extinction training in rats: a re-analysis

Abstract

Rationale: One approach to improving exposure therapy for anxiety disorders has focused on developing pharmacological adjuncts to enhance extinction, but these efforts have produced modest success in clinical trials. Understanding the factors that predict the efficacy of adjuncts will help to develop personalized treatments for anxiety.

Objectives: We assessed whether individual differences in within-session extinction (fear reduction during extinction training) predict the extent to which the neurotrophin fibroblast growth factor-2 (FGF2) enhances extinction recall in rats.

Methods: We re-analyzed data from five experiments that involved administering FGF2 immediately after extinction training; extinction recall was assessed the following day.

Results: Regression analyses revealed that fear responses at the end, but not the start, of extinction training predicted extinction recall in FGF2- but not vehicle-treated rats. Comparisons between FGF2- and vehicle-treated rats that exhibited better or worse extinction recall (determined by a median split in freezing during extinction recall) confirmed that FGF2-treated rats exhibiting better extinction recall had significantly lower freezing at the end of extinction training relative to FGF2-treated rats exhibiting poorer extinction recall. In contrast, vehicle-treated rats did not differ in within-session extinction based on their performance at extinction recall. Finally, even when classified as having poorer extinction recall, FGF2-treated rats had stronger extinction recall than vehicle-treated rats.

Conclusions: These results suggest that FGF2 may be most effective amongst rats that exhibit the lowest fear responses at the end of extinction training. Furthermore, FGF2 does not appear to exacerbate fear in rats that exhibit minimal fear reduction during extinction training.

Keywords: Anxiety; Exposure therapy; Fear extinction; Fibroblast growth factor 2; Within-session extinction.