Estrogen Receptor Gene Expression in Relation to Neuropsychiatric Disorders

Östlund, Hanna; Keller, Éva; Hurd, Yasmin L.

doi:10.1196/annals.1286.006

Cited by 239 publications

(165 citation statements)

References 42 publications

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“…In fact, estrogen receptors ␣ (ER␣) and ␤ (ER␤) are located in cAMYG, HIPP, VMN, PVN, PPN, and cortex (Keverne, 1988;Ostlund et al, 2003;Bao et al, 2005). Although previous work demonstrated excitatory effects of ER␣, ER␤ has shown nonexcitatory effects, thus suggesting that, through these receptors, estrogen may modulate autonomic and mood-related functions in relation to corticotropin-releasing factor (CRF) and norepinephrine (NE) release (Ostlund et al, 2003;Bao et al, 2005;Lund et al, 2005).…”

Section: Discussionmentioning

confidence: 90%

Hormonal Cycle Modulates Arousal Circuitry in Women Using Functional Magnetic Resonance Imaging

Goldstein¹,

Jerram²,

Poldrack³

et al. 2005

J. Neurosci.

321

254

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Sex-specific behaviors are in part based on hormonal regulation of brain physiology. This functional magnetic resonance imaging (fMRI) study demonstrated significant differences in activation of hypothalamic-pituitary-adrenal (HPA) circuitry in adult women with attenuation during ovulation and increased activation during early follicular phase. Twelve normal premenopausal women were scanned twice during the early follicular menstrual cycle phase compared with late follicular/midcycle, using negative valence/high arousal versus neutral visual stimuli, validated by concomitant electrodermal activity (EDA). Significantly greater magnitude of blood oxygenation level-dependent signal changes were found during early follicular compared with midcycle timing in central amygdala, paraventricular and ventromedial hypothalamic nuclei, hippocampus, orbitofrontal cortex (OFC), anterior cingulate gyrus (aCING), and peripeduncular nucleus of the brainstem, a network of regions implicated in the stress response. Arousal (EDA) correlated positively with brain activity in amygdala, OFC, and aCING during midcycle but not in early follicular, suggesting less cortical control of amygdala during early follicular, when arousal was increased. This is the first evidence suggesting that estrogen may likely attenuate arousal in women via cortical-subcortical control within HPA circuitry. Findings have important implications for normal sex-specific physiological functioning and may contribute to understanding higher rates of mood and anxiety disorders in women and differential sensitivity to trauma than men.

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Section: Discussionmentioning

confidence: 90%

Hormonal Cycle Modulates Arousal Circuitry in Women Using Functional Magnetic Resonance Imaging

Goldstein¹,

Jerram²,

Poldrack³

et al. 2005

J. Neurosci.

321

254

View full text Add to dashboard Cite

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“…The fact that E 2 rescues these extinction deficits suggests that E 2 enhances synaptic plasticity associated with extinction learning. Estrogen receptors a and b are expressed in the medial prefrontal cortex, amygdala, and hippocampus (Shughrue et al 1997;Ostlund et al 2003), structures that mediate extinction learning and consolidation . E 2 stimulates intracellular signaling cascades, growth factor induction, synaptogenesis, and protein synthesis (Spencer et al 2008;Frick 2012).…”

Section: Discussionmentioning

confidence: 99%

17β-Estradiol is necessary for extinction of cocaine seeking in female rats

et al. 2013

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Human and preclinical models of addiction demonstrate that gonadal hormones modulate acquisition of drug seeking. Little is known, however, about the effects of these hormones on extinction of drug-seeking behavior. Here, we investigated how 17b-estradiol (E 2 ) affects expression and extinction of cocaine seeking in female rats. Using a conditioned place preference (CPP) paradigm, ovariectomized rats were maintained throughout conditioning with 2 d of E 2 treatment followed by 2 d of vehicle treatment, or were injected with E 2 daily. Hormone injections were paired or explicitly unpaired with place conditioning sessions. Expression of a cocaine CPP was of equal magnitude regardless of conditioning protocol, suggesting that E 2 levels during conditioning did not affect subsequent CPP expression. During extinction, daily E 2 administration initially enhanced expression of the cocaine CPP, but resulted in significantly faster extinction compared to controls. Whereas E 2 -treated rats were extinguished within 8 d, vehicle-treated rats maintained CPP expression for more than a month, indicative of perseveration. To determine whether E 2 could rescue extinction in these rats, half were given daily E 2 treatment and half were given vehicle. E 2 -treated rats showed rapid extinction, whereas vehicle-treated rats continued to perseverate. These data demonstrate for the first time that E 2 is necessary for extinction of cocaine seeking in female rats, and that it promotes rapid extinction when administered daily. Clinically, these findings suggest that monitoring and maintaining optimal E 2 levels during exposure therapy would facilitate therapeutic interventions for female cocaine addicts.Gonadal hormones render women more susceptible than men to developing compulsive patterns of psychostimulant use. Natural fluctuations in levels of the primary ovarian hormones, estrogens and progesterone, account for this increased abuse liability. Higher levels of estrogens, and lower levels of progesterone, are associated with greater sensitivity to the euphorigenic properties of cocaine in women (Evans 2007). This increased sensitivity may contribute to why women, compared with men, start using cocaine regularly at a younger age (Chen and Kandel 2002), transition from use to abuse more quickly (McCance-Katz et al. 1999), experience greater craving in response to drug-associated cues (Robbins et al. 1999) and stress (Potenza et al. 2012;Waldrop et al. 2012), and exhibit more severe drug-seeking behavior upon relapse (Gallop et al. 2007). In contrast, more women than men remain abstinent after treatment (Weiss et al. 1997). Thus, women are both more susceptible to cocaine abuse and, paradoxically, more responsive to treatment.A substantial literature supports that estrogens mediate the enhancement of drug seeking observed in females (Febo et al. 2002;Larson et al. 2007;Segarra et al. 2010; Kerstetter and Kippin 2011), but little is known regarding the role of estrogens during treatment. Preclinically, treatment is modeled through ext...

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“…ER-a may be involved in automatic and reproductive functions, emotional expression and mood regulation, since this receptor subtype is predominantly expressed in hypothalamus and amygdala. 120 ER-b is highly expressed in hippocampus and thalamus, suggesting a role in cognition and memory. Compared to wild-type littermates, female ER-b knockout mice have been found to have significantly lower 5-HT and dopamine content in several brain regions, including reduced 5-HT in the hippocampus and a trend towards decreased 5-HT content in the dorsal raphe nucleus.…”

Section: Gendermentioning

confidence: 99%

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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Estrogen Receptor Gene Expression in Relation to Neuropsychiatric Disorders

Cited by 239 publications

References 42 publications

Hormonal Cycle Modulates Arousal Circuitry in Women Using Functional Magnetic Resonance Imaging

Hormonal Cycle Modulates Arousal Circuitry in Women Using Functional Magnetic Resonance Imaging

17β-Estradiol is necessary for extinction of cocaine seeking in female rats

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

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