Intraamygdala infusion of fibroblast growth factor 2 enhances extinction and reduces renewal and reinstatement in adult rats.

Abstract

Systemic fibroblast growth factor 2 (FGF2) has been shown to enhance extinction of conditioned fear and attenuate subsequent relapse in developing rats. However, it is not clear whether FGF2 has the same effect in adult rats, and furthermore, the neuroanatomical locus of the effect of FGF2 on extinction is unknown. These experiments examined the effect of 200 ng of FGF2, infused bilaterally into the basolateral complex of the amygdala (BLA), on the extinction of conditioned fear in adult rats. Experiment 1 confirmed that intra-BLA FGF2 significantly enhances extinction recall in adult rats, and extinction training is necessary for this effect to occur (FGF2 did not reduce conditioned freezing in the absence of extinction training). In Experiments 2 and 3, vehicle-treated rats were given four times the amount of extinction training as FGF2-treated rats to equate the strength of extinction between groups. In Experiment 2, rats were tested in both the extinction training context and the conditioning context to examine the effect of FGF2 on renewal of fear. In Experiment 3, the FGF2-treated rats and one-half of the vehicle-treated rats received a single unsignaled shock before test to examine the effect of FGF2 on reinstatement of fear. In both procedures, FGF2 administered immediately after extinction training significantly reduced relapse at test. These results support a growing body of evidence that FGF2 may be a potentially useful pharmacological adjunct to exposure-based therapies for anxiety disorders.