Influence of chronic stress on brain corticosteroid receptors and HPA axis activity.
Journal Title: Pharmacological Reports - Year 2013, Vol 65, Issue 5
Abstract
Background: Disruption of the glucocorticoid negative feedback system evoked in animals by chronic stress can be induced by downregulation of glucocorticoid receptors (GRs) in several brain regions. In the present study, the dynamics of the changes in GRs, in brain structures involved in stress reactions, prefrontal cortex, hippocampus and hypothalamus was compared with the peripheral hypothalamo-pituitary-adrenocortical (HPA) axis hormones response to chronic stress. Methods: Rats were exposed to 10 min restraint or restrained twice a day for 3, 7 or 14 days, and 24 h after the last stress session exposed to homotypic stress for 10 min. Control rats were not restrained. After rapid decapitation at 0, 1, 2, and 3 h after stress termination, trunk blood for plasma adrenocorticotropic hormone (ACTH) and corticosterone determinations was collected and prefrontal cortex, hippocampus and hypothalamus were excised and frozen. Plasma hormones were determined using commercially available kits and glucocorticoids and mineralocorticoids protein levels in brain structure samples were determined by western blot procedure. Results: Restraint stress alone significantly decreased glucocorticoid receptor (GR) level in prefrontal cortex and hippocampus, and increased mineralocorticoid receptor (MR) level in hypothalamus. Prior repeated stress for 3 days significantly increased GR protein level in hippocampus and diminished that level in hypothalamus in 7 days stressed rats. Acute stress-induced strong increase in plasma ACTH and corticosterone levels decreased to control level after 1 or 2 h, respectively. Prior repeated stress for 3 days markedly diminished the fall in plasma ACTH level and repeated stress for 7 days moderately deepened this decrease. Plasma ACTH level induced by homotypic stress in rats exposed to restraint for 3, 7, and 14 days did not markedly differ from its control level, whereas plasma corticosterone response was significantly diminished. The fast decrease of stress-induced high plasma ACTH and corticosterone levels was accompanied by a parallel decline of GR level only in prefrontal cortex but not in the hippocampus or hypothalamus. Conclusions: Comparison of the dynamics of changes in plasma ACTH and corticosterone level with respective alterations in GR and MR in brain structures suggests that the buffering effect of repeated stress depends on the period of habituation to stress and the brain structure involved in regulation of these stress response.
Authors and Affiliations
Anna Gądek-Michalska, Jadwiga Spyrka, Paulina Rachwalska, Joanna Tadeusz, Jan Bugajski
Keywords
Related Articles
- EP ID EP110056
- DOI -
- Views 98
- Downloads 0
Residual fraction of the area under the curve as a qualitative criterion in pharmacokinetic studies.
The aim of the present study was to determine whether the residual area under the curve (AUC(res%); expressed as % of total value of AUC) could be used as a parameter for the qualitative evaluation of pharmacokinetic stu...
Huntington's disease: pathogenesis to animal models.
Huntington's disease (HD) is an inherited genetic disorder, characterized by cognitive dysfunction and abnormal body movements called chorea. George Huntington, an Ohio physician, described the disease precisely in 1872....
Synergism between dexketoprofen and meloxicam in an orofacial formalin test was not modified by opioid antagonists.
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs for the management of acute and chronic pain. The role of the opioid system in the synergism between NSAIDs is not well characterized. M...
Inhibition of NAD(P)H oxidase attenuates aggregation of platelets from high-risk cardiac patients with aspirin resistance.
Up to one-third of serious vascular events in high-risk patients is attributable to a failure of aspirin (ASA) to suppress platelet aggregation. We hypothesized that inhibition of NAD(P)H oxidase may inhibit aggregation...
Neurochemical modulation of stress-induced cognitive inflexibility in a rat model of an attentional set-shifting task.
It is widely accepted that chronic stress, which is considered a risk factor for several neuropsychiatric disorders, may have detrimental effects on prefrontal functions. In animal models, chronic stress produces morphol...