The bed nucleus of stria terminalis and the amygdala as targets of antenatal glucocorticoids: implications for fear and anxiety responses

Source: Psychopharmacology

Abstract
Rationale  Several human and experimental studies have shown that early life adverse events can shape physical and mental health in adulthood.
Stress or elevated levels of glucocorticoids (GCs) during critical periods of development seem to contribute for the appearance
of neurospyschiatric conditions such as anxiety and depression, albeit the underlying mechanisms remain to be fully elucidated.

Objectives  The aim of the present study was to determine the long-term effect of prenatal exposure to dexamethasone- DEX (synthetic GC
widely used in clinics) in fear and anxious behavior and identify the neurochemical, morphological and molecular correlates.

Results  Prenatal exposure to DEX triggers a hyperanxious phenotype and altered fear behavior in adulthood. These behavioral traits
were correlated with increased volume of the bed nucleus of the stria terminalis (BNST), particularly the anteromedial subdivision
which presented increased dendritic length; in parallel, we found an increased expression of synapsin and NCAM in the BNST
of these animals. Remarkably, DEX effects were opposite in the amygdala, as this region presented reduced volume due to significant
dendritic atrophy. Albeit no differences were found in dopamine and its metabolite levels in the BNST, this neurotransmitter
was substantially reduced in the amygdala, which also presented an up-regulation of dopamine receptor 2.

Conclusions  Altogether, our results show that in utero DEX exposure can modulate anxiety and fear behavior in parallel with significant
morphological, neurochemical and molecular changes; importantly, GCs seem to differentially affect distinct brain regions
involved in this type of behaviors.

  • Content Type Journal Article
  • Category Original Investigation
  • Pages 1-11
  • DOI 10.1007/s00213-011-2494-y
  • Authors
    • Mário Oliveira, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
    • Ana-João Rodrigues, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
    • Pedro Leão, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
    • Diana Cardona, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
    • José Miguel Pêgo, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal
    • Nuno Sousa, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal

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