Short communicationPrenatal stress exacerbates the impact of an aversive procedure on the corticosterone response to stress in female rats
Introduction
Several lines of evidence demonstrate that certain psychiatric disorders are associated with alterations in hypothalamic-pituitary adrenal (HPA) function (de Kloet, 2008). Many depressed patients exhibit cortisol non-suppression in response to dexamethasone administration, suggesting an inhibition of negative feedback, while post-traumatic stress disorder (PTSD) patients, on the other hand, typically show enhanced cortisol suppression (Gillespie and Nemeroff, 2005, Yehuda et al., 2004). These two psychiatric disorders share common risk factors, such as being a woman (Gavranidou and Rosner, 2003) and exposure to stressful events in childhood (Heim and Nemeroff, 2001).
In animals, as in humans, HPA function is affected by gender and by early exposure to adverse events (Darnaudéry and Maccari, 2008, Kapoor et al., 2006, Louvart et al., 2006, Weinstock et al., 1992). The corticosterone response of female rats after an acute stress is of higher magnitude and duration than that of males (Louvart et al., 2006). However, 42 days after a traumatic procedure (an intense inescapable footshock followed by situational reminders), female rats exhibit increased negative feedback of the HPA axis whereas no effect is seen in male animals (Louvart et al., 2006). Prenatal restraint stress (PRS) induced by chronic restraint stress in pregnant rats is associated with HPA axis alterations in the offspring. Indeed, PRS animals display reduced levels of both mineralocorticoid and glucocorticoid receptors in the hippocampus, as well as prolonged stress-induced corticosterone secretion after restraint stress or exposure to novelty (Darnaudéry and Maccari, 2008). Moreover, PRS provokes depressive-like disturbances such as an increase in paradoxical sleep episodes and high levels of immobility in the forced swim test (Maccari and Morley-Fletcher, 2007). Recent studies suggest that the early environment could play a major role in the development of PTSD-like behaviors in animal models (Imanaka et al., 2006, Louvart et al., 2005a). Indeed, neonatal isolation significantly increases the contextual freezing observed in animals exposed to a single prolonged stress in adulthood (Imanaka et al., 2006). In the same way, after exposure to an intense footshock, female rats stressed in utero exhibit increased immobility in an aversive context, fail to habituate to a novel environment (Louvart et al., 2005a), and show a high preference for alcohol (Darnaudéry et al., 2007). Taken together, these results suggest that stress in early life can predispose animals to vulnerability to the negative effects of intense stress during adulthood.
Therefore, the aim of this study was to assess the long-term effects of a traumatic procedure on the corticosterone response to stress in female PRS rats. The corticosterone response to restraint stress was assessed 140 days post-shock in control and female PRS rats.
Section snippets
Methods
Animals were maintained on a 12 h light/dark cycle, with free access to food and water. Manipulation of the animals was carried out following the principles of laboratory animal care published by the French Ethical Committee and European Union norms (86/609/EEC). Nulliparous female Sprague–Dawley rats (Harlan, France) weighing 250 g were group-housed for 7 days after arrival to coordinate their estrus cycle. Females were then individually housed with a sexually experienced male rat for a complete
Results
As shown in Fig. 1A–C, corticosterone levels increased after 30 min of restraint stress in all experimental groups (time effect, F(3, 117) = 191.56, p < 0.001; post hoc Newman–Keul test, p < 0.001, 30 min vs. other time points). As expected, among No Shock groups (Fig. 1A), PRS rats exhibited higher plasma corticosterone levels (21.5 ± 3.0 μg/dl) than control females (12.1 ± 3.0 μg/dl), 120 min after the stress (group effect, F(1, 39) = 4.32, p < 0.05).
The aversive procedure affected the corticosterone response
Discussion
The present study aimed to evaluate the effects of the interaction between stress in early life and exposure to an intense footshock stress in adulthood, a proposed animal model of PTSD (Louvart et al., 2005b, Pynoos et al., 1996, Rasmussen et al., 2008), on the corticosterone response to stress in female rats. Our result reveals that in female rats, a traumatic procedure can induce a reversal of the prolongation of corticosterone secretion, a classic phenomenon described in PRS rats (
Conflict of interest
None declared.
Acknowledgements
We thank D. Deschamps and S. Lefèvre for animal care and F. Paquet, A. Bous and Dr. H. Bouwalerh for the technical help. English editing assistance was provided by Gap Junction (www.gap-junction.com).
Role of the funding sources: Funding for this study was provided by the CNRS (programme Sciences biomédicales, Santé et Société) and the University of Lille 1. Hélène Louvart was supported by a Fondation pour la Recherche Médicale fellowship program (Action dynamique en Psychiatrie). These funding
References (23)
- et al.
Epigenetic programming of the stress response in male and female rats by prenatal restraint stress
Brain Res. Rev.
(2008) - et al.
Impact of an intense stress on ethanol consumption in female rats characterized by their pre-stress preference: modulation by prenatal stress
Brain Res.
(2007) - et al.
The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies
Biol. Psychiatry
(2001) - et al.
Importance of early environment in the development of post-traumatic stress disorder-like behaviors
Behav. Brain Res.
(2006) - et al.
Stress–restress: effects on ACTH and fast feedback
Psychoneuroendocrinology
(1997) - et al.
Prenatal stress affects behavioral reactivity to an intense stress in adult female rats
Brain Res.
(2005) - et al.
Long-term behavioural alterations in female rats after a single intense footshock followed by situational reminders
Psychoneuroendocrinology
(2005) - et al.
Effects of a single footshock followed by situational reminders on HPA axis and behaviour in the aversive context in male and female rats
Psychoneuroendocrinology
(2006) - et al.
A behavioral animal model of posttraumatic stress disorder featuring repeated exposure to situational reminders
Biol. Psychiatry
(1996) - et al.
Acoustic startle amplitude predicts vulnerability to develop post-traumatic stress hyper-responsivity and associated plasma corticosterone changes in rats
Psychoneuroendocrinology
(2008)
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