BACKGROUND: Genetic factors and early-life adversity are critical in the etiology of @entity1316 and @entity734 . Because of their role in the transduction of stress responses, glucocorticoid hormones and their receptors could serve as both genetic factors and mediators of environmental influences. We have shown that constitutive overexpression of the glucocorticoid receptor (GR) in forebrain results in increased emotional reactivity and lability in @entity19 . Here, we asked whether there was a critical period for the emergence of this phenotype. METHODS: We generated a @entity19 line with inducible GR overexpression specifically in forebrain. @entity148 -like behaviors and @entity2072 -induced sensitization were assessed in adult @entity19 following GR overexpression during different periods in development. The molecular basis of the behavioral phenotype was examined using microarray analyses of dentate gyrus and nucleus accumbens. RESULTS: Transient overexpression of GR during early life led to increased @entity148 and @entity2072 sensitization, paralleling the phenotype of lifelong GR overexpression. This increased emotional reactivity was not observed when GR overexpression was induced after weaning. Glucocorticoid receptor overexpression in early life is sufficient to alter gene expression patterns for the rest of the animal's life, with dentate gyrus being more responsive than nucleus accumbens. The altered transcripts are implicated in GR and axonal guidance signaling in dentate gyrus and @entity935 receptor signaling in nucleus accumbens. CONCLUSIONS: Transient overexpression of GR early in life is both necessary and sufficient for inducing transcriptome-wide changes in the brain and producing a lifelong increase in vulnerability to @entity148 and drugs of abuse.

Early-life forebrain glucocorticoid receptor overexpression increases anxiety behavior and XXXX sensitization.

@entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity935 :: ('MESH:D004298', 'Chemical') :: ['dopamine'] @entity1316 :: ('MESH:D019964', 'Disease') :: ['mood disorders'] @entity2072 :: ('MESH:D003042', 'Chemical') :: ['cocaine'] @entity148 :: ('MESH:D001008', 'Disease') :: ['Anxiety', 'anxiety'] @entity734 :: ('MESH:D019966', 'Disease') :: ['substance abuse']
@entity2072 :: (MESH:D003042,Chemical) :: ['cocaine']
