Decreased Sensitivity to Glucocorticoid Fast Feedback in Chronically Stressed Rats

Young, Elizabeth A.; Akana, Susan F.; Dallman, Mary F.

doi:10.1159/000125388

Cited by 125 publications

(48 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In a number of animal studies, stress-elevated corticosterone levels are associated with down-regulated hippocampal GR mRNA and receptor number, indicating that this reduction in receptors results in reduced efficacy of corticosterone negative feedback [12, 29, 30]. In our study, rats stressed through stress paradigm A had elevated plasma corticosterone levels when assayed on the 8th or 10th day of stress, but they were adapted to this mild stress on day 14, as judged by their normal basal corticosterone levels.…”

Section: Discussionmentioning

confidence: 99%

Long-Lasting Effects of Stress on Glucocorticoid Receptor Gene Expression in the Rat Brain

Kitraki¹,

Karandrea²,

Kittas³

1999

Neuroendocrinology

109

View full text Add to dashboard Cite

Stressful stimuli are known to affect glucocorticoid receptor (GR) mRNA levels in the rat brain. The aim of this study was to examine the duration of chronic stress-induced changes in GR gene expression in the male rat hippocampus and cerebellum. By using in situ hybridization histochemistry, we detected a statistically significant down-regulation of GR mRNA both in the hippocampus and in the cerebellum of rats stressed for 8, 10 and 14 days. The same degree of down-regulation could also be detected in the above brain areas of rats stressed for 14 days and left undisturbed for 48 h or 8 days after stress. To examine the effects of subsequent stressors on the expression of down-regulated GR mRNA in the hippocampus of chronically stressed rats, we determined, by Northern blotting, GR mRNA levels in the hippocampi of rats stressed for 14 days and subsequently exposed to either short- or long-duration stressors. The down-regulated levels of GR mRNA remained practically unaffected when a subsequent new stressor was applied. Our results show that chronic stress-induced down-regulation of GR mRNA in the rat brain can be extended for periods longer than the initial/causative stimulus, irrespective of the presence of a novel stimulus.

show abstract

Section: Discussionmentioning

confidence: 99%

Long-Lasting Effects of Stress on Glucocorticoid Receptor Gene Expression in the Rat Brain

Kitraki¹,

Karandrea²,

Kittas³

1999

Neuroendocrinology

109

View full text Add to dashboard Cite

show abstract

“…In response to chronic stress, a reduction in both GR and MR numbers 14 has been reported particularly in the hippocampus (the site of the 'fast feedback' inhibition) 1417 . Chronic treatment with ECS is an exception but although hippocampal corticosteroid receptors are not down-regulated, CRH mRNA is increased as is adrenal volume and the net effect is an increase both in basal corticosteroid secretion and the corticosteroid response to ECS 18 . Both 'fast' and 'delayed' feedback inhibition are impaired in animals exposed to chronic stress 1 '.…”

Section: Hpa Activation In Response To Chronic Stress -Animal Studiesmentioning

confidence: 95%

The neuroendocrinology of depression and chronic stress

Checkley¹

1996

British Medical Bulletin

283

147

View full text Add to dashboard Cite

This chapter will review basic and clinical studies of the social, genetic and developmental influences upon the reactivity of the hypothalamic pituitary adrenal (HPA) axis and the relationship of these to depression. Significant advances have taken place in each of these areas and it is now possible to interlink many of these areas of work. In order to do so, this chapter will be organised into five sections.The first section will show how the neuroendocrinology of chronic stress is characterised by an up-regulation of the central drive to the HPA axis in conjunction with downregulation of its negative feedback control.The second will show that very similar processes occur in depressive illness.The third section will describe social, developmental and genetic influences on the HPA axis both in experimental animals and in man.The fourth will show how activation of the HPA axis can influence the development of animal models of depression as well as the onset and perpetuation of clinical depression.The final section will draw together an overall hypothesis and indicate the potential for new treatments for depression that arise from this work. The neuroendocrinology of acute and chronic stressThe secretion of corticosteroid hormones (predominantly cortisol in man and corticosterone in the rat) is the most important endocrine component of the response to stress and the one that is most necessary for successful adaptation: the acute response has a time course of 1-2 h and the chronic response one of days or weeks. HPA activation in response to acute stress -animal studiesThe central drive to the stress response of the HPA axis is organised by the parvocellular component of the paraventricular nucleus (PVN) of the hypothalamus. Some of these cells synthesise corticotropin releasing Postal address: hormone (CRH) alone and some both CRH and arginine vasopressin Prof Stuart chockley, (AVP), but both types of cells project to the external zone of the median institute of Psychiatry, eminence and release their hormones into the hypophyseal portal system Denmark HiTLndo'n wm ch carries the hormones to the anterior pituitary gland. In response to SE5 8AF, UK an acute stress there is an increase in the synthesis of CRH mRNA and

show abstract

“…Sapolsky et al (1984b) have demonstrated that chronic immobilization stress downregulates glucocorticoid receptors in the brain. Furthermore, rats that were chronically exposed to footshock stress showed a decreased sensitivity to glucocorticoid negative feedback, indicating the involvement of glucocorticoid receptor downregulation (Young et al, 1990). Therefore, it is conceivable that part of the actions is mediated through the glucocorticoid receptor reduction in the chronically stressed rat brains.…”

Section: Chronic Stress Induces Working Memory Impairment Via a D1 Rementioning

confidence: 99%

Chronic Stress Induces Impairment of Spatial Working Memory Because of Prefrontal Dopaminergic Dysfunction

et al. 2000

View full text Add to dashboard Cite

Although the mechanism responsible for cognitive deficits in stress-related neuropsychiatric disorders has been obscure, prefrontal cortical (PFC) dopaminergic dysfunction is thought to be involved. In animals, the mesoprefrontal dopaminergic system is particularly vulnerable to stress, and chronic stress induces working memory impairment. However, the relation between the working memory impairment and altered dopaminergic activity in chronically stressed rats is unclear. Furthermore, the change of dopaminergic activity in the PFC induced by stress is thought to express as a stress response, not as a disorder of organic function. We have previously reported that chronic stress administered by water immersion and restraint for 4 weeks induces a organic disorder such as hippocampal neuronal degeneration. We therefore examined whether chronically stressed (4 weeks) and recovered (10 d) rats show a working memory impairment caused by reduced dopamine (DA) transmission in the PFC, as suspected in the neuropsychiatric disorders. The stress impaired the spatial working memory evaluated by T-maze task and induced a marked reduction of DA transmission concomitant with an increase in DA D1 receptor density in the PFC. This memory impairment was sufficiently ameliorated by intra-PFC infusion of 10 ng SKF 81297, a D1 receptor-specific agonist. Pretreatment with intraperitoneal injection of 20 g/kg SCH 23390, a D1 receptor antagonist, reversed the SKF 81297 response. These results indicate that chronic stress induces working memory impairment through a D1 receptor-mediated hypodopaminergic mechanism in the PFC. These findings provide important information for understanding of the mechanisms underlying PFC dysfunction in stress-related neuropsychiatric disorders.Key words: chronic stress; working memory; prefrontal cortex; dopaminergic neuron; D1 receptor; cognitive deficit Exposure to stress is known to precipitate or exacerbate many neuropsychiatric disorders such as depression, Parkinson's disease, schizophrenia, and others (Schwab and Zieper, 1965;Mazure, 1995). All these disorders involve a working memory deficit caused by prefrontal cortical (PFC) dysfunction (Mattes, 1980;Weinberger et al., 1986;Deutch, 1993;Fibiger, 1995). Several antidepressants increase dopamine (DA) levels in the PFC (Tanda et al., 1994), and raising the DA level in patients with Parkinson's disease with L-3,4-dihydroxyphenylalanine improves their working memory deficit (Lange et al., 1992). These findings suggest that a reduced dopaminergic transmission in the PFC is responsible for the working memory deficits in the neuropsychiatric disorders.In animals, reduced PFC dopaminergic function or blockade of DA receptor in the PFC of monkeys and rats impairs working memory function (Brozoski et al., 1979;Simon et al., 1980;Bubser and Schmidt, 1990), which supports the observations in the neuropsychiatric disorders. In addition, an exposure to acute stress in monkeys or rats has been reported to produce working memory impairment, which can be blocked by...

show abstract

Decreased Sensitivity to Glucocorticoid Fast Feedback in Chronically Stressed Rats

Cited by 125 publications

References 19 publications

Long-Lasting Effects of Stress on Glucocorticoid Receptor Gene Expression in the Rat Brain

Long-Lasting Effects of Stress on Glucocorticoid Receptor Gene Expression in the Rat Brain

The neuroendocrinology of depression and chronic stress

Chronic Stress Induces Impairment of Spatial Working Memory Because of Prefrontal Dopaminergic Dysfunction

Contact Info

Product

Resources

About