Effects of Mineralocorticoid and Glucocorticoid Receptor Blockade on Hypothalamic–Pituitary–Adrenal Function in Female Rats Prenatally Exposed to Ethanol

Glavas, Maria M.; Yu, Wayne; Weinberg, Joanne

doi:10.1111/j.1530-0277.2006.00236.x

Cited by 18 publications

(19 citation statements)

References 37 publications

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“…1B). These results demonstrate that corticosteroid receptor antagonists have no significant effect on CSD-induced adrenocortical activation, a result similar to those reported previously (Glavas et al, 2006; Moldow et al, 2005; Pace and Spencer, 2005; Weidenfeld and Feldman, 1993). Taken together, the present results suggest that both MRs and GRs did not play an important role in mediating suppressive effects of glucocorticoids on HPA axis function in the intense stimuli like CSD.…”

Section: Discussionsupporting

confidence: 92%

“…For example, stress-induced high plasma corticosterone levels were further exaggerated by treatment with either corticosteroid receptor antagonists alone or in combination (Ratka et al, 1989; Spencer et al, 1998). However, a no further change in plasma corticosterone levels was also reported in the animal stress models by similar treatments (Glavas et al, 2006; Moldow et al, 2005; Pace and Spencer, 2005; Weidenfeld and Feldman, 1993). In the present study, while plasma corticosterone levels in CSD rats treated with mifepristone or spironolactone alone were similarly increased as in CSD-alone rats, CSD rats treated with both mifepristone and spironolactone showed a lower plasma corticosterone level than that of the CSD-alone group.…”

Section: Discussionsupporting

confidence: 58%

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Chronic social defeat up-regulates expression of norepinephrine transporter in rat brains

Chen

Fan

Liu

et al. 2012

Neurochemistry International

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Stress has been reported to activate the locus coeruleus (LC)–noradrenergic system. However, the molecular link between chronic stress and noradrenergic neurons remains to be elucidated. In the present study adult Fischer 344 rats were subjected to a regimen of chronic social defeat (CSD) for 4 weeks. Measurements by in situ hybridization and Western blotting showed that CSD significantly increased mRNA and protein levels of the norepinephrine transporter (NET) in the LC region and NET protein levels in the hippocampus, frontal cortex and amygdala. CSD-induced increases in NET expression were abolished by adrenalectomy or treatment with corticosteroid receptor antagonists, suggesting the involvement of corticosterone and corticosteroid receptors in this upregulation. Furthermore, protein levels of protein kinase A (PKA), protein kinase C (PKC), and phosphorylated cAMP-response element binding (pCREB) protein were significantly reduced in the LC and its terminal regions by the CSD paradigm. Similarly, these reduced protein levels caused by CSD were prevented by adrenalectomy. However, effects of corticosteroid receptor antagonists on CSD-induced down-regulation of PKA, PKC, and pCREB proteins were not consistent. While mifeprestone and spironolactone, either alone or in combination, totally abrogate CSD effects on these protein levels of PKA, PKC and pCREB in the LC and those in the hippocampus, frontal cortex and amygdala, their effects on PKA and PKC in the hippocampus, frontal cortex and amygdala were region-dependent. The present findings indicate a correlation between chronic stress and activation of the noradrenergic system. This correlation and CSD-induced alteration in signal transduction molecules may account for their critical effects on the development of symptoms of major depression.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 58%

Chronic social defeat up-regulates expression of norepinephrine transporter in rat brains

Chen

Fan

Liu

et al. 2012

Neurochemistry International

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“…This suggests an alteration in MR-mediated CORT signalling, and perhaps an altered MR/GR balance (Sliwowska et al, 2008). In addition, we found that MR and GR blockade resulted in greater ACTH release in PAE females but not males under basal or pre-stress conditions, compared to their PF and C counterparts (Glavas et al, 2006), which is consistent with what was observed by Young et al (2004) among depressed populations, as described above.…”

Section: Prenatal Alcohol Exposure and Hpa Dysregulationsupporting

confidence: 90%

Prenatal alcohol exposure: Fetal programming and later life vulnerability to stress, depression and anxiety disorders

Hellemans

Śliwowska

Verma

et al. 2010

Neuroscience & Biobehavioral Reviews

Self Cite

291

232

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Children with Fetal Alcohol Spectrum Disorder (FASD) exhibit cognitive, neuropsychological and behavioral problems, and numerous secondary disabilities including depression and anxiety disorders. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is common in depression/anxiety, reflected primarily in increased HPA tone or activity. Prenatal alcohol exposure (PAE) increases HPA tone and results in HPA dysregulation throughout life, paralleling many of the HPA changes in depression/anxiety. We review data demonstrating altered HPA function and increased depression/anxiety in FASD. In the context of the stress-diathesis model, we discuss the hypothesis that fetal programming of the HPA axis by PAE alters neuroadaptive mechanisms that mediate the stress response, thus sensitizing the organism to stressors encountered later in life, and mediating, at least partly, the increased vulnerability to depression/anxiety disorders. Furthermore, we present evidence demonstrating sex-specific alterations in both hormonal and behavioral responsiveness to tasks measuring depressive- and anxiety-like behaviors in PAE offspring. Overall, the research suggests that the stress-diathesis model provides a powerful approach for elucidating mechanisms underlying the increased vulnerability to mental illness among individuals with FASD, and developing appropriate treatments for these individuals. Dr. Seymour Levine’s seminal work on the long-term consequences of early life experiences formed a framework for the development of the research described in this review.

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“…The decreased stress-responsiveness with mifepristone treatment is consistent with a previous report by (Ratka et al, 1989) in which animals treated systemically with mifepristone prior to exposure to novel environment displayed decreased stress-responsiveness (i.e., corticosterone) compared with vehicle treated animals. However, there are other reports whereby mifepristone increases neuroendocrine responsiveness to restraint stress in females prenatally exposed to ethanol (Glavas et al, 2006). …”

Section: Discussionmentioning

confidence: 99%

Mifepristone decreases depression-like behavior and modulates neuroendocrine and central hypothalamic–pituitary–adrenocortical axis responsiveness to stress

Wulsin

Herman

Solomon

2010

Psychoneuroendocrinology

113

110

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Summary Glucocorticoid dyshomeostasis is observed in a proportion of depressed individuals. As a result, glucocorticoid receptor (GR) antagonists are currently being tested as potential anti-depressants. The current study was designed to test the efficacy of mifepristone, a GR antagonist, in mitigating behavioral, neuroendocrine and central nervous system (CNS) responses to an acute stressor. Adult male rats were treated for five days with mifepristone (10 mg/kg) and then exposed to the forced swim test (FST). Treatment with mifepristone decreased immobility and increased swimming (but not climbing) behavior in the FST, consistent with antidepressant action. In addition, mifepristone dampened the ACTH response to FST exposure. In the CNS, mifepristone increased c-Fos expression in all subdivisions of the medial prefrontal cortex (mPFC) and decreased neuronal activity in some subdivisions of the hippocampus including the CA2, CA3, and hilus region of the dentate gyrus in animals exposed to FST. In contrast, mifepristone increased neuronal activity in the ventral subiculum (output region of the hippocampus) and decreased c-Fos expression in the central amygdala (CeA) in animals exposed to FST. These data suggest that antidepressant efficacy and perhaps HPA dampening properties of RU486 are related to alterations in key limbic circuits mediating CNS stress responses, resulting in enhanced stress inhibition (via the mPFC and ventral subiculum) as well as decreased stress excitation (central amygdala). Overall the data suggest that drugs targeting the glucocorticoid receptor may ameliorate stress dysfunction associated with depressive illness.

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Effects of Mineralocorticoid and Glucocorticoid Receptor Blockade on Hypothalamic–Pituitary–Adrenal Function in Female Rats Prenatally Exposed to Ethanol

Cited by 18 publications

References 37 publications

Chronic social defeat up-regulates expression of norepinephrine transporter in rat brains

Chronic social defeat up-regulates expression of norepinephrine transporter in rat brains

Prenatal alcohol exposure: Fetal programming and later life vulnerability to stress, depression and anxiety disorders

Mifepristone decreases depression-like behavior and modulates neuroendocrine and central hypothalamic–pituitary–adrenocortical axis responsiveness to stress

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