Pharmacological Inhibition of the Psychiatric Risk Factor FKBP51 Has Anxiolytic 
Properties.

Hartmann, Jakob; Wagner, Klaus V.; Gaali, Steffen; Kirschner, Alexander; Kozany, Christian; Ruhter, Gerd; Dedic, Nina; Häusl, Alexander S.; Hoeijmakers, Lianne; Westerholz, Sören; Namendorf, Christian; Gerlach, Tamara; Uhr, Manfred; Chen, Alon; Deussing, Jan M.; Holsboer, Florian; Hausch, Felix; Schmidt, Mathias V.

doi:10.1523/JNEUROSCI.4024-14.2015

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Pharmacological Inhibition of the Psychiatric Risk Factor FKBP51 Has Anxiolytic Properties.

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/persons/resource/persons80354

Hartmann, Jakob
Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons80573

Wagner, Klaus V.
Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons80330

Gaali, Steffen
Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons182844

Kirschner, Alexander
Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons80406

Kozany, Christian
Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons80298

Dedic, Nina
Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons135680

Häusl, Alexander S.
Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons142050

Hoeijmakers, Lianne
Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons138004

Westerholz, Sören
Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons80456

Namendorf, Christian
Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons80337

Gerlach, Tamara
Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons80563

Uhr, Manfred
Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons129892

Chen, Alon
Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons80301

Deussing, Jan M.
Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons80372

Holsboer, Florian
Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons80356

Hausch, Felix
Max Planck Institute of Psychiatry, Max Planck Society;

/persons/resource/persons80514

Schmidt, Mathias V.
Max Planck Institute of Psychiatry, Max Planck Society;

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Citation

Hartmann, J., Wagner, K. V., Gaali, S., Kirschner, A., Kozany, C., Ruhter, G., et al. (2015). Pharmacological Inhibition of the Psychiatric Risk Factor FKBP51 Has Anxiolytic Properties. The Journal of neuroscience: the official journal of the Society for Neuroscience, 35(24), 9007-16. doi:10.1523/JNEUROSCI.4024-14.2015.

Cite as: https://hdl.handle.net/11858/00-001M-0000-0028-5708-7

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.