High Corticosterone Levels in Prenatally Stressed Rats Predict Persistent Paradoxical Sleep Alterations

Dugovic, Christine; Maccari, Stefania; Weibel, Laurence; Turek, Fred W.; Reeth, Olivier Van

doi:10.1523/jneurosci.19-19-08656.1999

Cited by 151 publications

(93 citation statements)

References 55 publications

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“…HL and NHL mice exhibited different sleep structure and stability. The lighter and more fragmented sleep, and the decreased REM sleep latency in HL mice are in harmony with those of studies where helplessness was induced experimentally in rats (34,35). Moreover, alterations of sleep-wakefulness patterns in HL mice mimic to some extent those observed in depressed patients such as the enhanced REM sleep ''pressure'' and the sleep fragmentation (21).…”

Section: Discussionsupporting

confidence: 79%

Behavioral, neurochemical, and electrophysiological characterization of a genetic mouse model of depression

Yacoubi

Bouali

Popa

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

239

173

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Depression is a multifactorial illness and genetic factors play a role in its etiology. The understanding of its physiopathology relies on the availability of experimental models potentially mimicking the disease. Here we describe a model built up by selective breeding of mice with strikingly different responses in the tail suspension test, a stress paradigm aimed at screening potential antidepressants. Indeed, ''helpless'' mice are essentially immobile in the tail suspension test, as well as the Porsolt forced-swim test, and they show reduced consumption of a palatable 2% sucrose solution. In addition, helpless mice exhibit sleep-wakefulness alterations resembling those classically observed in depressed patients, notably a lighter and more fragmented sleep, with an increased pressure of rapid eye movement sleep. Compared with ''nonhelpless'' mice, they display higher basal seric corticosterone levels and lower serotonin metabolism index in the hippocampus. Remarkably, serotonin 1A autoreceptor stimulation induces larger hypothermia and inhibition of serotoninergic neuronal firing in the nucleus raphe dorsalis in helpless than in nonhelpless mice. Thus, helpless mice exhibit a decrease in serotoninergic tone, which evokes that associated with endogenous depression in humans. Finally, both the behavioral impairments and the serotoninergic dysfunction can be improved by chronic treatment with the antidepressant fluoxetine. The helpless line of mice may provide an opportunity to approach genes influencing susceptibility to depression and to investigate neurophysiological and neurochemical substrates underlying antidepressant effects.T he prevalence of depression worldwide is such that this disorder represents a major health problem. It is estimated, for example, that Ϸ10% of men and 20% of women in Western Europe will suffer from a major depressive episode at some time in their life. The monoamine hypothesis of depression suggests that one of the biological bases of affective disorders is a deficiency in the neurotransmitter serotonin (5-HT). During the past 40 yr, this hypothesis has been refined, as more experimental and clinical evidence has emerged. The selective 5-HT reuptake inhibitors, in particular, allowed important progress in our understanding of the role of 5-HT in depression. To some extent, the mechanism of action of 5-HT reuptake inhibitors, which are the most widely prescribed antidepressant drugs today, can be anticipated from our knowledge of the anatomy and chemistry of the central serotoninergic system. However, it must be accepted that extensive investigations have so far failed to find convincing evidence of a primary dysfunction of the serotoninergic system in patients with depression. Disturbances of sleep are typical for most depressed patients and belong to the core symptoms of the disorder. Polysomnographic sleep research has demonstrated that, besides disturbances of sleep continuity, depression is associated with a reduction of slow-wave sleep and a shortening of rapid eye movement (REM...

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Section: Discussionsupporting

confidence: 79%

Behavioral, neurochemical, and electrophysiological characterization of a genetic mouse model of depression

Yacoubi

Bouali

Popa

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

239

173

View full text Add to dashboard Cite

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“…50 Even in the absence of elevated HPA activity, however, it is noteworthy that CRH-COE hom -Nes and -Cam mice display increased spontaneous REM sleep as most other animal models of depression do. [51][52][53][54][55] It has been always difficult to dissociate the effects of each separate HPA hormone on sleep and to offer a mechanism how depression or stress promotes REM sleep. Exogenous administration of an unphysiologically high CRH dose triggers hyperarousal, leaving it unclear by which mechanism REM sleep is suppressed.…”

Section: Discussionmentioning

confidence: 99%

Conditional corticotropin-releasing hormone overexpression in the mouse forebrain enhances rapid eye movement sleep

et al. 2009

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Impaired sleep and enhanced stress hormone secretion are the hallmarks of stress-related disorders, including major depression. The central neuropeptide, corticotropin-releasing hormone (CRH), is a key hormone that regulates humoral and behavioral adaptation to stress. Its prolonged hypersecretion is believed to play a key role in the development and course of depressive symptoms, and is associated with sleep impairment. To investigate the specific effects of central CRH overexpression on sleep, we used conditional mouse mutants that overexpress CRH in the entire central nervous system (CRH-COE-Nes) or only in the forebrain, including limbic structures (CRH-COE-Cam). Compared with wild-type or control mice during baseline, both homozygous CRH-COE-Nes and -Cam mice showed constantly increased rapid eye movement (REM) sleep, whereas slightly suppressed non-REM sleep was detected only in CRH-COE-Nes mice during the light period. In response to 6-h sleep deprivation, elevated levels of REM sleep also became evident in heterozygous CRH-COE-Nes and -Cam mice during recovery, which was reversed by treatment with a CRH receptor type 1 (CRHR1) antagonist in heterozygous and homozygous CRH-COE-Nes mice. The peripheral stress hormone levels were not elevated at baseline, and even after sleep deprivation they were indistinguishable across genotypes. As the stress axis was not altered, sleep changes, in particular enhanced REM sleep, occurring in these models are most likely induced by the forebrain CRH through the activation of CRHR1. CRH hypersecretion in the forebrain seems to drive REM sleep, supporting the notion that enhanced REM sleep may serve as biomarker for clinical conditions associated with enhanced CRH secretion.

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“…127,159 Rat PS offspring show enhanced response to stress 126,127,135,155,160 and higher behavioral emotionality in several stressful situations. 155,159,[161][162][163][164] Adult PS offspring show many characteristics similar to those seen in depressed humans 165 including HPA dysregulations and anhedonic behaviors. 166,167 Abnormalities in brain neurotransmitter systems have also been reported, most importantly low central 5-HT activity in adult offspring after high maternal and fetal 5-HT.…”

Section: Stressmentioning

confidence: 93%

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

et al. 2006

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In recent years, the term serotonergic vulnerability (SV) has been used in scientific literature, but so far it has not been explicitly defined. This review article attempts to elucidate the SV concept. SV can be defined as increased sensitivity to natural or experimental alterations of the serotonergic (5-HTergic) system. Several factors that may disrupt the 5-HTergic system and hence contribute to SV are discussed, including genetic factors, female gender, personality characteristics, several types of stress and drug use. It is explained that SV can be demonstrated by means of manipulations of the 5-HTergic system, such as 5-HT challenges or acute tryptophan depletion (ATD). Results of 5-HT challenge studies and ATD studies are discussed in terms of their implications for the concept of SV. A model is proposed in which a combination of various factors that may compromise 5-HT functioning in one person can result in depression or other 5-HT-related pathology. By manipulating 5-HT levels, in particular with ATD, vulnerable subjects may be identified before pathology initiates, providing the opportunity to take preventive action. Although it is not likely that this model applies to all cases of depression, or is able to identify all vulnerable subjects, the strength of the model is that it may enable identification of vulnerable subjects before the 5-HT related pathology occurs. Molecular Psychiatry ( Keywords: serotonin; mood disorders; stress; genetics; sex; tryptophan Involvement of serotonin in depressionMood disorders are one of the most prevalent forms of mental illness. 1 According to the DSM-IV, the lifetime risk for major depressive disorder is between 10 and 25% for women and between 5 and 12% for men. 2 Depression has been studied intensively during the last few decades, but the psychological and neurobiological determinants of depression have not yet been precisely defined. Although several factors are known to contribute to the etiology of depression, it is not clear how these factors cause depression, and why some subjects become depressed while others remain unaffected. In terms of biological factors in the etiology of depression, there are several hypotheses. These include neurotransmitter dysfunctions (serotonin, 5-HT; dopamine, DA; norepinephrine, NE); dysregulations in hypothalamic-pituitary-adrenal (HPA) axis activity; and immune system imbalance. The aim of this article is not to discuss all of these hypotheses in detail, but to evaluate the role that serotonin may play within these hypothesized mechanisms.It is widely accepted that diminished serotonergic (5-HTergic) function is involved in the onset and course of depression. 3,4 The 5-HTergic system is a large and complex system. Although nearly all cell bodies of 5-HTergic neurons are located in the raphe nuclei in the brain stem, the axons of these neurons innervate almost the entire brain. The actions of 5-HT are mediated by 16 types and subtypes of receptors. 5 As the 5-HTergic system is assumed to be a modulatory system, the exact func...

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High Corticosterone Levels in Prenatally Stressed Rats Predict Persistent Paradoxical Sleep Alterations

Cited by 151 publications

References 55 publications

Behavioral, neurochemical, and electrophysiological characterization of a genetic mouse model of depression

Behavioral, neurochemical, and electrophysiological characterization of a genetic mouse model of depression

Conditional corticotropin-releasing hormone overexpression in the mouse forebrain enhances rapid eye movement sleep

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

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