Psychoneuroendocrinology
-
Psychoneuroendocrinology · Sep 2013
Comparative StudyDenial or receipt of expected reward through maternal contact during the neonatal period differentially affect the development of the rat amygdala and program its function in adulthood in a sex-dimorphic way.
Early experiences affect brain development and thus adult brain function and behavior. We employed a novel early experience model involving denial (DER) or receipt of expected reward (RER) through maternal contact in a T-maze. Exposure to the DER experience for the first time, on postnatal day 10 (PND10), was stressful for the pups, as assessed by increased corticosterone levels, and was accompanied by enhanced activation of the amygdala, as assessed by c-Fos immunohistochemistry. ⋯ On the other hand, the DER males, but not females showed an increased activation, as assessed by c-Fos expression, of the amygdala following fear conditioning. Our results show that the DER early experience programmed the function of the adult amygdala as to render it more sensitive to fearful stimuli. This programming by the DER early experience could be mediated through epigenetic modifications of histones leading to chromatin opening, as indicated by our results showing increased levels of phospho-acetyl-histone-3 in the amygdala of the DER males.
-
Psychoneuroendocrinology · Sep 2013
Cannabinoids and traumatic stress modulation of contextual fear extinction and GR expression in the amygdala-hippocampal-prefrontal circuit.
Considerable evidence suggests that cannabinoids modulate the behavioral and physiological response to stressful events. We have recently shown that activating the cannabinoid system using the CB1/CB2 receptor agonist WIN55,212-2 (WIN) in proximity to exposure to single-prolonged stress (SPS), a rat model of emotional trauma, prevented the stress-induced enhancement of acoustic startle response, the impairment in avoidance extinction and the enhanced negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis (Ganon-Elazar and Akirav, 2012). Some of the effects were found to be mediated by CB1 receptors in the basolateral amygdala (BLA). ⋯ We found that: (i) SPS impaired contextual fear extinction tested one week after trauma exposure and that WIN prevented the stress-induced impairment of extinction when microinjected immediately after trauma exposure into the BLA or hippocampus (5 μg), but not when microinjected into the PFC, (ii) the ameliorating effects of WIN on contextual extinction were prevented by blocking GRs in the BLA and hippocampus, and (iii) SPS up regulated GRs in the BLA, PFC and hippocampus and systemic WIN administration (0.5 mg/kg) after trauma exposure normalized GR levels in the BLA and hippocampus, but not in the PFC. Cannabinoid receptor activation in the aftermath of trauma exposure may regulate the emotional response to the trauma and prevent stress-induced impairment of extinction and GR up regulation through the mediation of CB1 receptors in the BLA and hippocampus. Taken together, the findings suggest that the interaction between the cannabinoid and glucocorticoid systems is crucial in the modulation of emotional trauma.
-
Psychoneuroendocrinology · Aug 2013
Analysis of baseline hypothalamic-pituitary-adrenal activity in late adolescence reveals gender specific sensitivity of the stress axis.
Dysfunctional regulation of the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as an important biological mechanism underlying stress-related diseases; however, a better understanding of the interlinked neuroendocrine events driving the release of cortisol by this stress axis is essential for progress in preventing or halting irreversible development of adverse HPA-function. We aimed to investigate basal HPA-activity in a normal population in late adolescence, the time of life believed to overlap with HPA-axis maturation and establishment of a lasting set point level of HPA function. A total of 1258 participants (mean age 16.6 years) recruited from the Western Australian Pregnancy (Raine) Cohort provided fasting morning blood and saliva samples for basal HPA activity assessment. ⋯ Free plasma cortisol, calculated from total circulating cortisol and CBG concentrations, was also significantly reduced in girls using oral contraceptives, possibly via an enhancing effect of oral contraceptives on blood CBG content. This study highlights a clear gender difference in HPA activity under non-stressful natural conditions. This finding may be relevant for research into sex-specific stress-related diseases with a typical onset in late adolescence.
-
Psychoneuroendocrinology · Jul 2013
The use of saliva for assessment of cortisol pulsatile secretion by deconvolution analysis.
Cortisol is the key effector molecule of the HPA axis and is secreted in a pulsatile manner in all species studied. In order to understand cortisol signalling in health and disease, detailed analysis of hormone pulsatility is necessary. To dissect cortisol pulsatility in plasma deconvolution techniques have been applied. ⋯ The deconvolution of the most distinct component of cortisol diurnal rhythm-cortisol awakening response (CAR), revealed an average 2.5±1.1 peaks based on the individual time for cortisol to return to baseline levels. In conclusion, deconvolution analysis of plasma and salivary cortisol concentration time series showed a close correlation and similar pulsatile characteristics between saliva and plasma cortisol. Similarly, Monte Carlo simulations revealed a high concordance between the peaks in these coupled time series suggesting that saliva is a suitable medium for subsequent deconvolution analysis yielding accurate and reliable models of cortisol secretion in particular during the morning hours.
-
Psychoneuroendocrinology · Jul 2013
Influence of stress on fear memory processes in an aversive differential conditioning paradigm in humans.
It is widely assumed that learning and memory processes play an important role in the pathogenesis, expression, maintenance and therapy of anxiety disorders, such as phobias or post-traumatic stress disorder (PTSD). Memory retrieval is involved in symptom expression and maintenance of these disorders, while memory extinction is believed to be the underlying mechanism of behavioral exposure therapy of anxiety disorders. There is abundant evidence that stress and stress hormones can reduce memory retrieval of emotional information, whereas they enhance memory consolidation of extinction training. ⋯ No group differences were observed with respect to extinction. In conclusion, the present study provides evidence that stress can reduce memory retrieval of conditioned fear in men. Our findings may contribute to the understanding of the effects of stress and glucocorticoids on fear symptoms in anxiety disorders and suggest that such effects may be sex-specific.