1. Academic Validation
  2. Pharmacological Inhibition of the Psychiatric Risk Factor FKBP51 Has Anxiolytic Properties

Pharmacological Inhibition of the Psychiatric Risk Factor FKBP51 Has Anxiolytic Properties

  • J Neurosci. 2015 Jun 17;35(24):9007-16. doi: 10.1523/JNEUROSCI.4024-14.2015.
Jakob Hartmann 1 Klaus V Wagner 2 Steffen Gaali 2 Alexander Kirschner 2 Christian Kozany 2 Gerd Rühter 3 Nina Dedic 2 Alexander S Häusl 2 Lianne Hoeijmakers 2 Sören Westerholz 2 Christian Namendorf 2 Tamara Gerlach 2 Manfred Uhr 2 Alon Chen 2 Jan M Deussing 2 Florian Holsboer 2 Felix Hausch 1 Mathias V Schmidt 1
Affiliations

Affiliations

  • 1 Max Planck Institute of Psychiatry, 80804 Munich, Germany, and jhartmann@psych.mpg.de hausch@psych.mpg.de mschmidt@psych.mpg.de.
  • 2 Max Planck Institute of Psychiatry, 80804 Munich, Germany, and.
  • 3 Lead Discovery Center GmbH, 44227 Dortmund, Germany.
Abstract

Anxiety-related psychiatric disorders represent one of the largest health burdens worldwide. Single nucleotide polymorphisms of the FK506 binding protein 51 (FKBP51) gene have been repeatedly associated with anxiety-related disorders and stress sensitivity. Given the intimate relationship of stress and anxiety, we hypothesized that amygdala FKBP51 may mediate anxiety-related behaviors. Mimicking the stress effect by specifically overexpressing FKBP51 in the basolateral amygdala (BLA) or central amygdala resulted in increased anxiety-related behavior, respectively. In contrast, application of a highly selective FKBP51 point mutant antagonist, following FKBP51(mut) BLA-overexpression, reduced the anxiogenic phenotype. We subsequently tested a novel FKBP51 antagonist, SAFit2, in wild-type mice via BLA microinjections, which reduced anxiety-related behavior. Remarkably, the same effect was observed following peripheral administration of SAFit2. To our knowledge, this is the first in vivo study using a specific FKBP51 antagonist, thereby unraveling the role of FKBP51 and its potential as a novel drug target for the improved treatment of anxiety-related disorders.

Keywords

FKBP51; PTSD; amygdala; antidepressants; anxiety.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-102080
    98.59%, FKBP51 Inhibitor