Psychoneuroendocrinology
-
Psychoneuroendocrinology · Jun 2013
Mineralocorticoid receptor antagonist spironolactone prevents chronic corticosterone induced depression-like behavior.
High level of serum corticosteroid is frequently associated with depression, in which a notable HPA (hypothalamus-pituitary-adrenal) axis hyperactivity is often observed. There are two types of corticosteroid receptors expressed in the hippocampus that provide potent negative feedback regulation on the HPA axis but dysfunction during depression, i.e. the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). The balance between hippocampal MR and GR during chronic stress plays an important role in the occurrence of depression. ⋯ On the other hand, co-administration of MR antagonist, spironolactone (25mg/kg, i.p. × 7 days) in corticosteroid-treated animals reduced immobility time in a forced-swimming test and improved performance in a novel object recognition test. In conclusion, we demonstrate that chronic corticosterone treatment triggers several depression-like behaviors, and in parallel, down-regulates MR expression in the hippocampus and hypothalamus. Administration of an MR antagonist confers an anti-depressant effect in chronic corticosterone-treated animals.
-
Psychoneuroendocrinology · Jun 2013
Neonatal amygdala lesions alter basal cortisol levels in infant rhesus monkeys.
The amygdala is mostly thought to exert an excitatory influence on the hypothalamic-pituitary-adrenal (HPA) axis, although its role regulating HPA basal tone is less clear, particularly during primate development. The current study examined the effects of neonatal amygdala lesions on basal HPA function and the postnatal testosterone (T) surge of rhesus monkeys reared with their mothers in large outdoor social groups. An early morning basal blood sample was collected at 2.5 months of age, whereas at 5 months samples were collected not only at sunrise, but also at mid-day and sunset to examine the diurnal rhythm of cortisol. ⋯ Instead, the diurnal cortisol rhythm of both males and females with amygdalectomy showed a blunted decline from mid-day to sunset compared to controls. These results indicate that neonatal amygdala damage alters basal HPA function in infant rhesus monkeys, affecting males only at early ages (at 2.5 months), while leaving the postnatal T surge intact, and resulting in a flattened diurnal rhythm in both genders at the later ages. Thus, the primate amygdala has a critical influence on the HPA axis in the first few months of life.
-
Psychoneuroendocrinology · Jun 2013
Effects of denial of reward through maternal contact in the neonatal period on adult hypothalamic-pituitary-adrenal axis function in the rat.
Emotional behavioral traits associated with stress response are well documented to be affected by early life events. In the present work, we used a novel paradigm of neonatal experience, in which pups were trained in a T-maze and either received (RER rats) or were denied (DER) the reward of maternal contact, during postnatal days 10-13. We then evaluated stress coping and key factors controlling the function of the hypothalamic-pituitary-adrenal axis in adulthood. ⋯ In addition, the DER neonatal experience induced an increase in hippocampal GR but a decrease in CRH-R1 immunopositive cells in the CA1 area of the hippocampus and the central amygdala. Overall, these data show a distinct stress response profile in the DER male rats, characterized by passive coping during the forced swim, increased hormonal response following stress, increased inhibitory control through GR and an indirect contribution of CRH-R1, the latter two factors resulting in a modified regulation of the response termination. It thus appears that DER rats have an enhanced potential for appropriate reactivity upon an incoming challenge, while maintaining in parallel an adequate control of the duration of their stress responses.
-
Psychoneuroendocrinology · Jun 2013
Importance of epigenetic mechanisms in visceral pain induced by chronic water avoidance stress.
Epigenetic molecular mechanisms, which include DNA methylation and histone deacetylation, are implicated in the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Previously, we demonstrated that repeated water avoidance stress (WAS), a validated model of chronic psychological stress, induces heightened visceral pain behaviors in rodents that resemble irritable bowel syndrome (IBS) sequelae. However, the involvement of epigenetic molecular mechanisms in the pathophysiology of stress-induced visceral pain has not been explored. ⋯ Compared to SHAM controls, methylation of the GR gene was increased following WAS while expression of the GR gene was decreased. Methylation of the CRF promoter was decreased with WAS with a concomitant increase in CRF expression. This study demonstrates the involvement of central epigenetic mechanisms in regulating stress-induced visceral hypersensitivity and provides a foundation for exploring the epigenetic mechanisms that may contribute to IBS-like symptomatology.