TY - JOUR
T1 - Exogenous prenatal corticosterone exposure mimics the effects of prenatal stress on adult brain stress response systems and fear extinction behavior
AU - Bingham, Brian C.
AU - Sheela Rani, C. S.
AU - Frazer, Alan
AU - Strong, Randy
AU - Morilak, David A.
N1 - Funding Information:
This work was supported by research grant W81XWH-08-2-0118 , awarded to the STRONG STAR Multidisciplinary PTSD Research Consortium by the Department of Defense through the U.S. Army Medical Research and Materiel Command , Congressionally Directed Medical Research Programs , Psychological Health and Traumatic Brain Injury Research Program . The funding source had no role in study design, data collection, analysis or interpretation of data, nor in the preparation of or decision to submit the paper for publication. Prior to submission, the manuscript was reviewed and approved by the publication committee of the STRONG STAR Consortium, which is represented by the final attribution in the author list “for the STRONG STAR Consortium”.
PY - 2013/11
Y1 - 2013/11
N2 - Exposure to early-life stress is a risk factor for the development of cognitive and emotional disorders later in life. We previously demonstrated that prenatal stress (PNS) in rats results in long-term, stable changes in central stress-response systems and impairs the ability to extinguish conditioned fear responding, a component of post-traumatic stress disorder (PTSD). Maternal corticosterone (CORT), released during prenatal stress, is a possible mediator of these effects. The purpose of the present study was to investigate whether fetal exposure to CORT at levels induced by PNS is sufficient to alter the development of adult stress neurobiology and fear extinction behavior. Pregnant dams were subject to either PNS (60. min immobilization/day from ED 14-21) or a daily injection of CORT (10. mg/kg), which approximated both fetal and maternal plasma CORT levels elicited during PNS. Control dams were given injections of oil vehicle. Male offspring were allowed to grow to adulthood undisturbed, at which point they were sacrificed and the medial prefrontal cortex (mPFC), hippocampus, hypothalamus, and a section of the rostral pons containing the locus coeruleus (LC) were dissected. PNS and prenatal CORT treatment decreased glucocorticoid receptor protein levels in the mPFC, hippocampus, and hypothalamus when compared to control offspring. Both treatments also decreased tyrosine hydroxylase levels in the LC. Finally, the effect of prenatal CORT exposure on fear extinction behavior was examined following chronic stress. Prenatal CORT impaired both acquisition and recall of cue-conditioned fear extinction. This effect was additive to the impairment induced by previous chronic stress. Thus, these data suggest that fetal exposure to high levels of maternal CORT is responsible for many of the lasting neurobiological consequences of PNS as they relate to the processes underlying extinction of learned fear. The data further suggest that adverse prenatal environments constitute a risk factor for PTSD-like symptomatology, especially when combined with chronic stressors later in life.
AB - Exposure to early-life stress is a risk factor for the development of cognitive and emotional disorders later in life. We previously demonstrated that prenatal stress (PNS) in rats results in long-term, stable changes in central stress-response systems and impairs the ability to extinguish conditioned fear responding, a component of post-traumatic stress disorder (PTSD). Maternal corticosterone (CORT), released during prenatal stress, is a possible mediator of these effects. The purpose of the present study was to investigate whether fetal exposure to CORT at levels induced by PNS is sufficient to alter the development of adult stress neurobiology and fear extinction behavior. Pregnant dams were subject to either PNS (60. min immobilization/day from ED 14-21) or a daily injection of CORT (10. mg/kg), which approximated both fetal and maternal plasma CORT levels elicited during PNS. Control dams were given injections of oil vehicle. Male offspring were allowed to grow to adulthood undisturbed, at which point they were sacrificed and the medial prefrontal cortex (mPFC), hippocampus, hypothalamus, and a section of the rostral pons containing the locus coeruleus (LC) were dissected. PNS and prenatal CORT treatment decreased glucocorticoid receptor protein levels in the mPFC, hippocampus, and hypothalamus when compared to control offspring. Both treatments also decreased tyrosine hydroxylase levels in the LC. Finally, the effect of prenatal CORT exposure on fear extinction behavior was examined following chronic stress. Prenatal CORT impaired both acquisition and recall of cue-conditioned fear extinction. This effect was additive to the impairment induced by previous chronic stress. Thus, these data suggest that fetal exposure to high levels of maternal CORT is responsible for many of the lasting neurobiological consequences of PNS as they relate to the processes underlying extinction of learned fear. The data further suggest that adverse prenatal environments constitute a risk factor for PTSD-like symptomatology, especially when combined with chronic stressors later in life.
KW - Corticosterone
KW - Disorder
KW - Fear conditioning
KW - Fear extinction
KW - Glucocorticoids
KW - Post-traumatic stress
KW - Prenatal stress
KW - Stress vulnerability
KW - Tyrosine hydroxylase
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UR - http://www.scopus.com/inward/citedby.url?scp=84886099588&partnerID=8YFLogxK
U2 - 10.1016/j.psyneuen.2013.07.003
DO - 10.1016/j.psyneuen.2013.07.003
M3 - Article
C2 - 23937971
AN - SCOPUS:84886099588
SN - 0306-4530
VL - 38
SP - 2746
EP - 2757
JO - Psychoneuroendocrinology
JF - Psychoneuroendocrinology
IS - 11
ER -