Exogenous prenatal corticosterone exposure mimics the effects of prenatal stress on adult brain stress response systems and fear extinction behavior
Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, United States. Psychoneuroendocrinology
(Impact Factor: 4.94).
08/2013; 38(11). DOI: 10.1016/j.psyneuen.2013.07.003
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 (60min immobilization/day from ED 14-21) or a daily injection of CORT (10mg/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.
Available from: Xiaobai Li
- "The results indicated that prenatal stress was not associated with increased anxiety-like behaviors, deficits in learning, or retention during contextual fear conditioning in both male and female offspring (Wilson et al., 2013). However, in some previous studies, prenatal stress resulted in several behavioral anomalies, including enhanced conditioned fear (Bingham et al., 2013; Griffin et al., 2003), and impaired fear extinction (Li et al., 2014), suggesting prenatal stress enhanced anxiety-like behavior. The reasons for this discrepancy are unclear, but differences in animal strains, stressor administration schedules, duration, timing and intensity of stimuli are possible factors (Charil et al., 2010; Markham and Koenig, 2011). "
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ABSTRACT: Severe adverse life events during pregnancy may increase the risk of anxiety disorders in the offspring. Glutamate receptors are neurobiological targets in anxiety disorders. In this study, we investigated the effects of prenatal chronic mild stress (PCMS) on anxiety-like behavior by using elevated plus maze (EPM), and evaluated the effects of PCMS and/or anxiogenic challenge on glutamate receptors in different brain regions. Our results showed that PCMS increased anxiety-like behavior in both male and female offspring. Moreover, compared with the male naïve rats, male EPM rats showed a significant reduction of mGluR2/3 in the prefrontal cortex, mGluR1 and mGluR2/3 in the hippocampus, and increments of mGluR5, NR1, NR2B and PSD95 in the amygdala. In contrast, compared with female naïve rats, female EPM rats showed decreased levels of mGluR5 in the hippocampus, and mGluR2/3 and mGluR5 in the prefrontal cortex, and increased levels of NR2B and PSD95 in the amygdala. Furthermore, PCMS seemed not to affect the baseline expression of glutamate receptors in adult offspring, but induced significant alterations of them triggered by anxiogenic challenge with a sex difference. These data strengthen the pathophysiological hypothesis that prenatal stress as a risk factor involves in the development of anxiety disorder in the offspring.
Copyright © 2015. Published by Elsevier Ltd.
International Journal of Developmental Neuroscience 01/2015; 41. DOI:10.1016/j.ijdevneu.2015.01.003 · 2.58 Impact Factor
Available from: Bahadir Suleyman
- "In addition , 5 mg/kg corticosterone was administered ip to the ACK-30 and ACK-60 group rats. CORT was used at doses of, 3, 10 and higher in the literature  . One hour after CORT injection, 30 mg/kg ketamine was administered ip to the ACK-30 group and 60 mg/kg to the ACK-60 group. "
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ABSTRACT: This study investigated whether or not the anesthetic effect of ketamine in rats is dependent on adrenal gland hormones. The study was performed on two main rat groups, intact and adrenalectomized. Rat were divided into subgroups and given appropriate doses of ketamine, metyrapone or metyrosine. Durations of anesthesia in the groups were then recorded. Endogenous catecholamine levels were measured in samples taken from peripheral blood. This experimental results showed that ketamine did not induce anesthesia in intact rats at doses of 15 or 30 mg/kg, and that at 60 mg/kg anesthesia was established for only 11 min. However, ketamine induced significant anesthesia even at a dose of 30 mg/kg in animals in which production of endogenous catecholamine (adrenalin, noradrenalin dopamine) was inhibited with metyrosine at a level of 45-47%. Ketamine at 60 mg/kg in animals in which endogenous catecholamine was inhibited at a level of 45-47% established anesthesia for 47.6 min. However, ketamine at 30 and 60 mg/kg induced longer anesthesia in adrenalectomized rats with higher noradrenalin and dopamine levels but suppressed adrenalin production. Adrenalin plays an important role in the control of duration of ketamine anesthesia, while noradrenalin, dopamine and corticosterone have no such function. If endogenous adrenalin is suppressed, ketamine can even provide sufficient anesthesia at a 2-fold lower dose. This makes it possible for ketamine to be used in lengthy surgical procedures.
Medical Hypotheses 07/2014; 83(1). DOI:10.1016/j.mehy.2014.03.033 · 1.07 Impact Factor
Available from: Karen E Chapman
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ABSTRACT: Glucocorticoids are steroid hormones, essential in mammals to prepare for life after birth. Blood levels of glucocorticoids (cortisol in most mammals including humans; corticosterone in rats and mice) rise dramatically shortly before birth. This is mimicked clinically in the routine administration of synthetic glucocorticoids to pregnant women threatened by a preterm birth or to preterm infants to improve neonatal survival. Whilst effects on lung are well documented and essential for postnatal survival, those on heart are less well known. Here we review recent evidence for a crucial role for glucocorticoids in late gestational heart maturation. Either insufficient or excessive glucocorticoid exposure prior to birth may alter the normal glucocorticoid-regulated trajectory of heart maturation with potential life-long consequences.
Journal of Molecular Endocrinology 12/2013; 52(2). DOI:10.1530/JME-13-0204 · 3.08 Impact Factor
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