Prenatal stress induces long term stress vulnerability, compromising stress response systems in the brain and impairing extinction of conditioned fear after adult stress

M. K. Green, C. S.S. Rani, A. Joshi, A. E. Soto-Piña, P. A. Martinez, A. Frazer, R. Strong, D. A. Morilak

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

Stress is a risk factor for the development of affective disorders, including depression, post-traumatic stress disorder, and other anxiety disorders. However, not all individuals who experience either chronic stress or traumatic acute stress develop such disorders. Thus, other factors must confer a vulnerability to stress, and exposure to early-life stress may be one such factor. In this study we examined prenatal stress (PNS) as a potential vulnerability factor that may produce stable changes in central stress response systems and susceptibility to develop fear- and anxiety-like behaviors after adult stress exposure. Pregnant Sprague-Dawley rats were immobilized for 1 h daily during the last week of pregnancy. Controls were unstressed. The male offspring were then studied as adults. As adults, PNS or control rats were first tested for shock-probe defensive burying behavior, then half from each group were exposed to a combined chronic plus acute prolonged stress (CAPS) treatment, consisting of chronic intermittent cold stress (4 °C, 6 h/d, 14 days) followed on day 15 by a single session of sequential acute stressors (social defeat, immobilization, cold swim). After CAPS or control treatment, different groups were tested for open field exploration, social interaction, or cued fear conditioning and extinction. Rats were sacrificed at least 5 days after behavioral testing for measurement of tyrosine hydroxylase (TH) and glucocorticoid receptor (GR) expression in specific brain regions, and plasma adrenocorticotropic hormone (ACTH) and corticosterone. Shock-probe burying, open field exploration and social interaction were unaffected by any treatment. However, PNS elevated basal corticosterone, decreased GR protein levels in hippocampus and prefrontal cortex, and decreased TH mRNA expression in noradrenergic neurons in the dorsal pons. Further, rats exposed to PNS plus CAPS showed attenuated extinction of cue-conditioned fear. These results suggest that PNS induces vulnerability to subsequent adult stress, resulting in an enhanced fear-like behavioral profile, and dysregulation of brain noradrenergic and hypothalamic-pituitary-adrenal axis (HPA) activity.

Original languageEnglish (US)
Pages (from-to)438-451
Number of pages14
JournalNeuroscience
Volume192
DOIs
StatePublished - Sep 29 2011

Keywords

  • Fear extinction
  • HPA axis
  • Prenatal stress
  • Traumatic stress
  • Tyrosine hydroxylase
  • Vulnerability

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Prenatal stress induces long term stress vulnerability, compromising stress response systems in the brain and impairing extinction of conditioned fear after adult stress'. Together they form a unique fingerprint.

Cite this