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. Author manuscript; available in PMC: 2018 Jan 30.
Published in final edited form as: Biol Psychiatry. 2016 Sep 15;80(6):419–421. doi: 10.1016/j.biopsych.2016.07.010

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Normal or Low-Anxiety Phenotype FGF2 less effective (1) FGF2 blocks anxiety (Cortney A. Turner, Ph.D., et al., unpublished data, 2016)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.