Pharmacological Inhibition of the Psychiatric Risk Factor FKBP51 Has Anxiolytic Properties.
J Neurosci
; 35(24): 9007-16, 2015 Jun 17.
Article
em En
| MEDLINE
| ID: mdl-26085626
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ansiedade
/
Ansiolíticos
/
Proteínas de Ligação a Tacrolimo
Tipo de estudo:
Etiology_studies
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Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article