Psychoneuroendocrinology
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Psychoneuroendocrinology · Jul 2008
Mice selected for high versus low stress reactivity: a new animal model for affective disorders.
Affective disorders such as major depression are among the most prevalent and costly diseases of the central nervous system, but the underlying mechanisms are still poorly understood. In recent years, it has become evident that alterations of the stress hormone system, in particular dysfunctions (hyper- or hypo-activity) of the hypothalamic-pituitary-adrenal (HPA) axis, play a prominent role in the development of major depressive disorders. Therefore, we aimed to generate a new animal model comprising these neuroendocrine core symptoms in order to unravel parameters underlying increased or decreased stress reactivity. ⋯ For example, monitoring the circadian rhythm of glucocorticoid secretion revealed clearly increased trough levels in HR mice, resulting in a flattened diurnal rhythm, again adding to the neuroendocrine similarities to patients suffering from melancholic depression. Taken together, our results suggest that distinct mechanisms influencing the function and regulation of the HPA axis are involved in the respective behavioral and neurobiological endophenotypes. Thus, the generated HR/IR/LR mouse lines can be a valuable model to elucidate molecular genetic, neuroendocrine, and behavioral parameters associated with altered stress reactivity, thereby improving our understanding of affective disorders, presumably including the symptomatology and pathophysiology of specific subtypes of major depression.
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Psychoneuroendocrinology · Jul 2008
Randomized Controlled TrialHPA axis activation by a socially evaluated cold-pressor test.
The cold-pressor test (CPT) in which subjects immerse their hand in ice water is among the most commonly used laboratory stressors. While the CPT elicits strong sympathetic nervous system activation, cortisol elevations indicative for the reactivity of the hypothalamus-pituitary-adrenal (HPA) axis are moderate to low in response to the CPT. In the present study, we assessed whether cortisol responses to the CPT can be increased by adding social-evaluative elements. ⋯ Social evaluation during hand immersion in warm water did not affect saliva cortisol levels suggesting that both social evaluation and a challenge are required for HPA axis activation. These findings indicate that the incorporation of social-evaluative elements increases HPA axis responses to the CPT. The SECPT can serve as a tool for future stress research.
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Psychoneuroendocrinology · Jul 2008
Chronic psychosocial stress affects corticotropin-releasing factor in the paraventricular nucleus and central extended amygdala as well as urocortin 1 in the non-preganglionic Edinger-Westphal nucleus of the tree shrew.
Stressful stimuli evoke neuronal and neuroendocrine responses helping an organism to adapt to changed environmental conditions. Chronic stressors may induce maladaptive responses leading to psychiatric diseases, such as anxiety and major depression. A suitable animal model to unravel mechanisms involved in the control of adaptation to chronic stress is the psychological subordination stress in the male tree shrew. ⋯ In the pPVN, the number of CRF-immunoreactive neurons and the specific signal density of CRF-immunoreactive fiber terminals in the CeA were strongly reduced (-300 and -40%, respectively; P<0.05), whereas no significant difference in CRF fiber density was found in BNSTdl. The npEW revealed 4 times less Ucn1-immunoreactive neurons (P<0.05). These clear effects on both Ucn1- and CRF-neuropeptide contents may reflect a crucial mechanism enabling the animal to adapt successfully to the stressors, and point to the significance of the pPVN, CeA and npEW in stress-induced brain diseases.