Table 1. Complex Interplay Between the Anxiety State of the Animal and the Regulation of the HPA Axis.
Interplay | Normally Regulated HPA Axis | Chronically Activated HPA Axis or Chronic Stress |
---|---|---|
High-Anxiety Phenotype | FGF2 blocks anxiety (1,3) | FGF2 blocks anxiety (2) |
GR antagonist blocks anxiety (5) | GR antagonist prevents anxiolytic effect of FGF2 (2) | |
GR: detector of threat | GR: mediator of negative feedback | |
Are FGF2 and GR actions sequential or independent mechanisms? | FGF2 actions mediated via GR in genetic model. Is this evident in environmental models of chronic stress? | |
Normal or Low-Anxiety Phenotype | FGF2 less effective (1) | FGF2 blocks anxiety (Cortney A. Turner, Ph.D., et al., unpublished data, 2016) |
GR antagonist less effective (5) | GR antagonist ineffective (9) | |
What is the relationship between FGF2 and GR signaling? Could they be additive or synergistic in further lowering anxiety? | What is the relationship between FGF2 and GR signaling in nonanxious phenotype during chronic, high-stress conditions? |
FGF2, fibroblast growth factor 2; GR, glucocorticoid receptor; HPA, hypothalamic-pituitary-adrenal.