WorldWideScience

Sample records for hpa-axis hormones oxytocin

  1. Effects of thermal environment on HPA-axis hormones, oxytocin and behavioral activity in peri-parturient sows

    DEFF Research Database (Denmark)

    Malmkvist, Jens; Damgaard, Birthe Marie; Pedersen, Lene Juul

    2009-01-01

    Provision of additional floor heating (33 to 34C) at birth and during the early postnatal hours is favorable for newborn piglets of domestic sows (Sus scrofa). We investigated whether this relatively high temperature influenced sow behavior and physiology around farrowing. Half of 28 second......-parity pregnant sows were randomly chosen to be exposed to floor heating 12 h after onset of nest building and until 48 h after birth of the first piglet (treatment = HEAT), whereas the rest of the sows entered the control group (treatment = CONT) with no floor heating. Hourly blood sampling from 8 h before...... and until 24 h after the birth of the first piglet was used for investigation of temporal changes in plasma concentrations of oxytocin, cortisol, and ACTH. In addition, occurrence and duration of sow postures were recorded -8 h to +48 h relative to the birth of first piglet. There was a clear temporal...

  2. Stressor-specific effects of sex on HPA axis hormones and activation of stress-related neurocircuitry.

    Science.gov (United States)

    Babb, Jessica A; Masini, Cher V; Day, Heidi E W; Campeau, Serge

    2013-11-01

    Experiencing stress can be physically and psychologically debilitating to an organism. Women have a higher prevalence of some stress-related mental illnesses, the reasons for which are unknown. These experiments explore differential HPA axis hormone release in male and female rats following acute stress. Female rats had a similar threshold of HPA axis hormone release following low intensity noise stress as male rats. Sex did not affect the acute release, or the return of HPA axis hormones to baseline following moderate intensity noise stress. Sensitive indices of auditory functioning obtained by modulation of the acoustic startle reflex by weak pre-pulses did not reveal any sexual dimorphism. Furthermore, male and female rats exhibited similar c-fos mRNA expression in the brain following noise stress, including several sex-influenced stress-related regions. The HPA axis response to noise stress was not affected by stage of estrous cycle, and ovariectomy significantly increased hormone release. Direct comparison of HPA axis hormone release to two different stressors in the same animals revealed that although female rats exhibit robustly higher HPA axis hormone release after restraint stress, the same effect was not observed following moderate and high intensity loud noise stress. Finally, the differential effect of sex on HPA axis responses to noise and restraint stress cannot readily be explained by differential social cues or general pain processing. These studies suggest the effect of sex on acute stress-induced HPA axis hormone activity is highly dependent on the type of stressor.

  3. Association of HPA axis hormones with copeptin after psychological stress differs by sex.

    Science.gov (United States)

    Spanakis, Elias K; Wand, Gary S; Ji, Nan; Golden, Sherita Hill

    2016-01-01

    Copeptin levels are elevated in severe medical conditions, an effect that is attributed to elevated arginine vasopressin (AVP) levels in response to physiological stress, resulting in activation of hypothalamus-pituitary-adrenal (HPA) axis. In the current study, we wanted to determine if copeptin is responsive to psychological stress, correlates with cortisol and adrenocorticotropin hormone (ACTH), and if associations differed by sex. In a cross-sectional study that included 100 healthy men (41%) and women (59%) (aged 18-30 years; mean 24.6 ± 3 years), who underwent the Trier Social Stress Test (TSST), we examined the association between percent change (peak-baseline/baseline) in copeptin levels and percent change in log ACTH and cortisol. Three baselines samples were drawn followed by blood sampling at 20, 35, 50, 65 and 85 min after TSST. There was a significant positive association between the percent change in copeptin and the percent change in log-transformed salivary cortisol (β-coefficient=0.95; p=0.02). The association between percent change in copeptin and log-transformed serum cortisol was not statistically significant in the overall population. There was a trend for a non-significant association between percent change in copeptin and percent change in log-transformed ACTH (β-coefficient=1.14; p=0.06). In males, there was a significant positive association between the percent change in copeptin levels and log-transformed salivary (β-coefficient=1.33, p=0.016) and serum cortisol (β-coefficient=0.69, p=0.01), whereas in women there was no statistically significant association. We found a significant positive association between percent change in copeptin and percent change in salivary and serum cortisol among males only. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Beyond the HPA-axis: The role of the gonadal steroid hormone receptors in modulating stress-related responses in an animal model of PTSD.

    Science.gov (United States)

    Fenchel, Daphna; Levkovitz, Yechiel; Vainer, Ella; Kaplan, Zeev; Zohar, Joseph; Cohen, Hagit

    2015-06-01

    The hypothalamic-pituitary-adrenal (HPA) axis, which plays a major role in the response to stress, and the hypothalamic-pituitary-gonadal (HPG) axis are closely linked with the ability to inhibit the other. Testosterone, a product of the HPG, has many beneficial effects beyond its functions as a sex hormone including anti-anxiety properties. In this study we examined the effect of stress exposure on gonadal hormones, and their efficacy in modulating anxiety-like response in an animal model of PTSD. Male rats were exposed to predator scent stress, followed by analysis of brain expression of androgen receptor (AR) receptor and estrogen receptor α (ERα). The behavioral effects of immediate treatment with testosterone, testosterone receptor antagonist (flutamide) or vehicle were evaluated using the elevated plus-maze, acoustic startle response and trauma-cue response. Levels of circulating corticosterone and testosterone were also measured after treatment. The behavioral effects of delayed testosterone treatment were explored in the same manner. We report that animals whose behavior was extremely disrupted (EBR) selectively displayed significant down-regulation of AR and ERα in the hippocampus. Immediate treatment with flutamide or delayed treatment with testosterone significantly increased prevalence rates of minimal behavioral response (MBR) and decreased prevalence of EBR with favorable behavioral results. Testosterone levels were higher in control un-exposed animals, while corticosterone was higher in control exposed animals. This study suggests that gonadal steroid hormones are involved in the neurobiological response to predator scent stress and thus warrant further study as a potential therapeutic avenue for the treatment of anxiety-related disorders. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  5. [Effects of electroacupuncture at "Yishu" (EX-B 3) on the relative hormones of HPA axis in rats with type-2 diabetes mellitus].

    Science.gov (United States)

    Gao, Shana; Li, Rui; Tian, Huan-huan; Pei, En-shi; Cao, Bing-yan; Wu, Yan

    2014-11-01

    ). Four weeks after the intervention, except that the rat's body mass in the normal group continued to increase, body mass in the model group, medication group and each electroacupuncture group were significantly reduced (Pelectroacupuncture at "Pishu" (BL 20) group and electroacupuncture at "Yishu" (EX-B 3) group were obviously reduced (Pelectroacupuncture at "Yishu" (EX-B 3) group was lower than that in the medication group and electroacupuncture at "Shenshu" (BL 23) group (both Pelectroacupuncture at "Yishu" (EX-B 3) group were reduced (Pelectroacupuncture at "Shenshu" (BL 23) group (both Pelectroacupuncture at "Shenshu" (BL 23) group (Pelectroacupuncture at "Pishu" (BL 20) group and electroacupuncture at "Yishu (EX-B 3)" group were evidently increased (Pelectroacupuncture at "Yishu" (EX-B 3) group (Pelectroacupuncture at "Yishu" (EX-B 3) group was lower than that in the medication group and electroacupuncture at "Shenshu" (BL 23) group (Pelectroacupuncture at "Yishu" (EX-B 3) group was lower than that in the medication group and electroacupuncture at "Pishu" (BL 20) group (both PElectroacupuncture at "Yishu" (EX-B 3) could reduce the level of CORT to improve the insulin resistance in rats with T2DM, improve insulin sensitivity index, regulate blood lipid metabolism and relieve the hyperactivity of the HPA axis.

  6. Binge-pattern alcohol exposure during puberty induces long-term changes in HPA axis reactivity.

    Directory of Open Access Journals (Sweden)

    Magdalena M Przybycien-Szymanska

    2011-04-01

    Full Text Available Adolescence is a dynamic and important period of brain development however, little is known about the long-term neurobiological consequences of alcohol consumption during puberty. Our previous studies showed that binge-pattern ethanol (EtOH treatment during pubertal development negatively dysregulated the responsiveness of the hypothalamo-pituitary-adrenal (HPA axis, as manifested by alterations in corticotrophin-releasing hormone (CRH, arginine vasopressin (AVP, and corticosterone (CORT during this time period. Thus, the primary goal of this study was to determine whether these observed changes in important central regulators of the stress response were permanent or transient. In this study, juvenile male Wistar rats were treated with a binge-pattern EtOH treatment paradigm or saline alone for 8 days. The animals were left undisturbed until adulthood when they received a second round of treatments consisting of saline alone, a single dose of EtOH, or a second binge-pattern treatment paradigm. The results showed that pubertal binge-pattern EtOH exposure induced striking long-lasting alterations of many HPA axis parameters. Overall, our data provide strong evidence that binge-pattern EtOH exposure during pubertal maturation has long-term detrimental effects for the healthy development of the HPA axis.

  7. Oxytocin is a cardiovascular hormone

    Directory of Open Access Journals (Sweden)

    Gutkowska J.

    2000-01-01

    Full Text Available Oxytocin (OT, a nonapeptide, was the first hormone to have its biological activities established and chemical structure determined. It was believed that OT is released from hypothalamic nerve terminals of the posterior hypophysis into the circulation where it stimulates uterine contractions during parturition, and milk ejection during lactation. However, equivalent concentrations of OT were found in the male hypophysis, and similar stimuli of OT release were determined for both sexes, suggesting other physiological functions. Indeed, recent studies indicate that OT is involved in cognition, tolerance, adaptation and complex sexual and maternal behaviour, as well as in the regulation of cardiovascular functions. It has long been known that OT induces natriuresis and causes a fall in mean arterial pressure, both after acute and chronic treatment, but the mechanism was not clear. The discovery of the natriuretic family shed new light on this matter. Atrial natriuretic peptide (ANP, a potent natriuretic and vasorelaxant hormone, originally isolated from rat atria, has been found at other sites, including the brain. Blood volume expansion causes ANP release that is believed to be important in the induction of natriuresis and diuresis, which in turn act to reduce the increase in blood volume. Neurohypophysectomy totally abolishes the ANP response to volume expansion. This indicates that one of the major hypophyseal peptides is responsible for ANP release. The role of ANP in OT-induced natriuresis was evaluated, and we hypothesized that the cardio-renal effects of OT are mediated by the release of ANP from the heart. To support this hypothesis, we have demonstrated the presence and synthesis of OT receptors in all heart compartments and the vasculature. The functionality of these receptors has been established by the ability of OT to induce ANP release from perfused heart or atrial slices. Furthermore, we have shown that the heart and large vessels

  8. Neuroactive steroids modulate HPA axis activity and cerebral brain-derived neurotrophic factor (BDNF) protein levels in adult male rats.

    Science.gov (United States)

    Naert, Gaëlle; Maurice, Tangui; Tapia-Arancibia, Lucia; Givalois, Laurent

    2007-01-01

    Depression is characterized by hypothalamo-pituitary-adrenocortical (HPA) axis hyperactivity. In this major mood disorder, neurosteroids and neurotrophins, particularly brain-derived neurotrophic factor (BDNF), seem to be implicated and have some antidepressant effects. BDNF is highly involved in regulation of the HPA axis, whereas neurosteroids effects have never been clearly established. In this systematic in vivo study, we showed that the principal neuroactive steroids, namely dehydroepiandrosterone (DHEA), pregnenolone (PREG) and their sulfate esters (DHEA-S and PREG-S), along with allopregnanolone (ALLO), stimulated HPA axis activity, while also modulating central BDNF contents. In detail, DHEA, DHEA-S, PREG, PREG-S and ALLO induced corticotropin-releasing hormone (CRH) and/or arginine vasopressin (AVP) synthesis and release at the hypothalamic level, thus enhancing plasma adrenocorticotropin hormone (ACTH) and corticosterone (CORT) concentrations. This stimulation of the HPA axis occurred concomitantly with BDNF modifications at the hippocampus, amygdala and hypothalamus levels. We showed that these neurosteroids induced rapid effects, probably via neurotransmitter receptors and delayed effects perhaps after metabolization in other neuroactive steroids. We highlighted that they had peripheral effects directly at the adrenal level by inducing CORT release, certainly after estrogenic metabolization. In addition, we showed that, at the dose used, only DHEA, DHEA-S and PREG-S had antidepressant effects. In conclusion, these results highly suggest that part of the HPA axis and antidepressant effects of neuroactive steroids could be mediated by BDNF, particularly at the amygdala level. They also suggest that neurosteroids effects on central BDNF could partially explain the trophic properties of these molecules.

  9. HPA axis reactivity to pharmacologic and psychological stressors in euthymic women with histories of postpartum versus major depression.

    Science.gov (United States)

    Ferguson, Elizabeth H; Di Florio, Arianna; Pearson, Brenda; Putnam, Karen T; Girdler, Susan; Rubinow, David R; Meltzer-Brody, Samantha

    2017-06-01

    It is unclear whether women with a history of postpartum depression (PPD) have residual, abnormal hypothalamic-pituitary-adrenal (HPA) axis reactivity, as has been reported in major depression (MDD). Further unclear is whether the abnormalities in HPA axis reactivity associated with MDD represent a stable, underlying predisposition or a state-dependent phenomenon. This study sought the following: (1) to determine if euthymic postpartum women with a history of depression have an abnormal HPA axis reactivity to pharmacologic and psychological challenges and (2) to compare HPA reactivity in women with histories of PPD versus MDD. As a secondary objective, we wanted to determine the influence of trauma history on HPA axis function. Forty-five parous (12-24 months postpartum), euthymic women with history of MDD (n = 15), PPD (n = 15), and controls (n = 15) completed pharmacologic (dexamethasone/corticotropin-releasing hormone (CRH) test [DEX/CRH]) and psychological (Trier social stress test [TSST]) challenges during the luteal phase. Outcome measures were cortisol and adrenocorticotropic hormone (ACTH) response after DEX/CRH, and blood pressure, heart rate, epinephrine, norepinephrine, and cortisol response during the TSST. All groups had robust cortisol and ACTH response to DEX/CRH and cortisol response to TSST. Groups did not differ significantly in cortisol or ACTH response to DEX/CRH or in blood pressure, heart rate, epinephrine, norepinephrine, or cortisol response to TSST. Cortisol/ACTH ratio did not differ significantly between groups. Trauma history was associated with decreased cortisol response to DEX/CRH in women with histories of MDD, which was not significant after correction (F 8,125 , p = 0.02, Greenhouse-Geisser corrected p = 0.11). Currently euthymic women with histories of MDD or PPD did not demonstrate residual abnormal stress responsivity following administration of either a pharmacologic or psychological stressor.

  10. Oxytocin: Old Hormone, New Drug

    Directory of Open Access Journals (Sweden)

    Jolanta Gutkowska

    2009-12-01

    Full Text Available Oxytocin (OT, traditionally associated with reproductive functions, was revisited recently, and several new functions in cardiovascular regulation were discovered. These functions include stimulation of the cardioprotective mediators nitric oxide (NO and atrial natriuretic peptide. OT’s cardiovascular outcomes comprise: (i natriuresis, (ii blood pressure reduction, (iii negative inotropic and chronotropic effects, (iv parasympathetic neuromodulation, (v NO pathway involvement in vasodilatation and endothelial cell growth, (vi anti-inflammatory and (vii antioxidant activities as well as (viii metabolic effects. In addition, we have reported abundant OT in the early developing heart with its capacity to generate cardiomyocytes (CMs from mouse embryonic stem cells and stem cells residing in the heart. OT increases glucose uptake by cultured CMs, in normal, hypoxic and even in insulin resistance conditions. In experimentally-induced myocardial infarction in rats, continuous in vivo OT delivery improves the cardiac healing process and cardiac work, diminishes inflammation, and stimulates angiogenesis. Therefore, in pathological situations, OT plays an anti-inflammatory and cardioprotective role, enhancing vascular and metabolic functions, with potential therapeutic application(s.

  11. Dietary Manipulations That Induce Ketosis Activate the HPA Axis in Male Rats and Mice: A Potential Role for Fibroblast Growth Factor-21.

    Science.gov (United States)

    Ryan, Karen K; Packard, Amy E B; Larson, Karlton R; Stout, Jayna; Fourman, Sarah M; Thompson, Abigail M K; Ludwick, Kristen; Habegger, Kirk M; Stemmer, Kerstin; Itoh, Nobuyuki; Perez-Tilve, Diego; Tschöp, Matthias H; Seeley, Randy J; Ulrich-Lai, Yvonne M

    2018-01-01

    In response to an acute threat to homeostasis or well-being, the hypothalamic-pituitary-adrenocortical (HPA) axis is engaged. A major outcome of this HPA axis activation is the mobilization of stored energy, to fuel an appropriate behavioral and/or physiological response to the perceived threat. Importantly, the extent of HPA axis activity is thought to be modulated by an individual's nutritional environment. In this study, we report that nutritional manipulations signaling a relative depletion of dietary carbohydrates, thereby inducing nutritional ketosis, acutely and chronically activate the HPA axis. Male rats and mice maintained on a low-carbohydrate high-fat ketogenic diet (KD) exhibited canonical markers of chronic stress, including increased basal and stress-evoked plasma corticosterone, increased adrenal sensitivity to adrenocorticotropin hormone, increased stress-evoked c-Fos immunolabeling in the paraventricular nucleus of the hypothalamus, and thymic atrophy, an indicator of chronic glucocorticoid exposure. Moreover, acutely feeding medium-chain triglycerides (MCTs) to rapidly induce ketosis among chow-fed male rats and mice also acutely increased HPA axis activity. Lastly, and consistent with a growing literature that characterizes the hepatokine fibroblast growth factor-21 (FGF21) as both a marker of the ketotic state and as a key metabolic stress hormone, the HPA response to both KD and MCTs was significantly blunted among mice lacking FGF21. We conclude that dietary manipulations that induce ketosis lead to increased HPA axis tone, and that the hepatokine FGF21 may play an important role to facilitate this effect. Copyright © 2018 Endocrine Society.

  12. Inflammation Is an Important Covariate for the Crosstalk of Sleep and the HPA Axis in Rheumatoid Arthritis.

    Science.gov (United States)

    Straub, Rainer H; Detert, Jaqueline; Dziurla, René; Fietze, Ingo; Loeschmann, Peter-Andreas; Burmester, Gerd R; Buttgereit, Frank

    2017-01-01

    Rheumatoid arthritis (RA) patients have sleep problems, and inflammation influences sleep. We demonstrated that sleep quality improves during intensified treatment with methotrexate (MTX) or etanercept (ETA). Since the hypothalamic-pituitary-adrenal (HPA) axis is involved in sleep regulation, this study investigated the interrelation between sleep parameters, inflammation as objectified by C-reactive protein (CRP), and serum cortisol and adrenocorticotropic hormone (ACTH) levels. Thirty-one eligible patients (disease activity score, DAS28CRP ≥3.2) participated in a 16-week, open, prospective study of HPA axis outcomes. MTX was initiated in 15 patients (female-to-male ratio 9/6) and ETA in 16 patients (14/2). Clinical, laboratory (after polysomnography [PSG] between 8 and 9 a.m.), sleep (PSG), and HPA axis outcome parameters (after PSG between 8 and 9 a.m.) were recorded at baseline and week 16. Clinical characteristics of patients markedly improved throughout the study (e.g., DAS28CRP: p Sleep efficiency and wake time after sleep onset markedly improved in the ETA group. Serum cortisol and ACTH did not change during observation. At baseline, serum cortisol levels were negatively correlated to sleep efficiency; this may depend on inflammation, because controlling for CRP eliminated this negative correlation. After ETA treatment, serum cortisol had a high positive correlation with total sleep time, sleep efficiency, and a negative correlation with wake time before and after sleep onset, which was not eliminated by controlling for CRP. In RA patients, the data indicate that inflammation is an important covariate for the crosstalk of sleep and the HPA axis. © 2017 S. Karger AG, Basel.

  13. Dysregulation of the HPA axis as a core pathophysiology mediating co-morbid depression in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Xin eDu

    2015-03-01

    Full Text Available There is increasing evidence of prodromal manifestation of neuropsychiatric symptoms in a variety of neurodegenerative diseases such as Parkinson’s disease and Huntington’s disease. These affective symptoms may be observed many years before the core diagnostic symptoms of the neurological condition. It is becoming more apparent that depression is a significant modifying factor of the trajectory of disease progression, and even treatment outcomes. It is therefore crucial that we understand the potential pathophysiologies related to the primary condition, which could contribute to the development of depression. The hypothalamic-pituitary-adrenal (HPA axis is a key neuroendocrine signaling system involved in physiological homeostasis and stress response. Disturbances of this system lead to severe hormonal imbalances, and the majority of such patients also present with behavioural deficits and/or mood disorders. Dysregulation of the HPA axis is also strongly implicated in the pathology of major depressive disorder. Consistent with this, anti-depressant drugs such as the selective serotonin reuptake inhibitors (SSRI have been shown to alter HPA axis activity. In this review, we will summarize the current state of knowledge regarding HPA axis pathology in Alzheimer’s, Parkinson’s and Huntington’s diseases, differentiating between prodromal and later stages of disease progression where possible. Both clinical and preclinical evidence will be examined, but we highlight animal model studies as being particularly useful for uncovering novel mechanisms of pathology related to co-morbid mood disorders. Finally, we purpose utilizing the pre-clinical evidence to better inform prospective, intervention studies.

  14. Impaired glucocorticoid-mediated HPA axis negative feedback induced by juvenile social isolation in male rats.

    Science.gov (United States)

    Boero, Giorgia; Pisu, Maria Giuseppina; Biggio, Francesca; Muredda, Laura; Carta, Gianfranca; Banni, Sebastiano; Paci, Elena; Follesa, Paolo; Concas, Alessandra; Porcu, Patrizia; Serra, Mariangela

    2018-05-01

    We previously demonstrated that socially isolated rats at weaning showed a significant decrease in corticosterone and adrenocorticotropic hormone (ACTH) levels, associated with an enhanced response to acute stressful stimuli. Here we shown that social isolation decreased levels of total corticosterone and of its carrier corticosteroid-binding globulin, but did not influence the availability of the free active fraction of corticosterone, both under basal conditions and after acute stress exposure. Under basal conditions, social isolation increased the abundance of glucocorticoid receptors, while it decreased that of mineralocorticoid receptors. After acute stress exposure, socially isolated rats showed long-lasting corticosterone, ACTH and corticotrophin releasing hormone responses. Moreover, while in the hippocampus and hypothalamus of group-housed rats glucocorticoid receptors expression increased with time and reached a peak when corticosterone levels returned to basal values, in socially isolated rats expression of glucocorticoid receptors did not change. Finally, social isolation also affected the hypothalamic endocannabinoid system: compared to group-housed rats, basal levels of anandamide and cannabinoid receptor type 1 were increased, while basal levels of 2-arachidonoylglycerol were decreased in socially isolated rats and did not change after acute stress exposure. The present results show that social isolation in male rats alters basal HPA axis activity and impairs glucocorticoid-mediated negative feedback after acute stress. Given that social isolation is considered an animal model of several neuropsychiatric disorders, such as generalized anxiety disorder, depression, post-traumatic stress disorder and schizophrenia, these data could contribute to better understand the alterations in HPA axis activity observed in these disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. HPA AXIS RELATED GENES AND RESPONSE TO PSYCHOLOGICAL THERAPIES: GENETICS AND EPIGENETICS

    NARCIS (Netherlands)

    Roberts, Susanna; Keers, Robert; Lester, Kathryn J.; Coleman, Jonathan R. I.; Breen, Gerome; Arendt, Kristian; Blatter-Meunier, Judith; Cooper, Peter; Creswell, Cathy; Fjermestad, Krister; Havik, Odd E.; Herren, Chantal; Hogendoorn, Sanne M.; Hudson, Jennifer L.; Krause, Karen; Lyneham, Heidi J.; Morris, Talia; Nauta, Maaike; Rapee, Ronald M.; Rey, Yasmin; Schneider, Silvia; Schneider, Sophie C.; Silverman, Wendy K.; Thastum, Mikael; Thirlwall, Kerstin; Waite, Polly; Eley, Thalia C.; Wong, Chloe C. Y.

    2015-01-01

    Hypothalamic-pituitary-adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive

  16. From Malthus to motive: how the HPA axis engineers the phenotype, yoking needs to wants

    NARCIS (Netherlands)

    Pecoraro, Norman; Dallman, Mary F.; Warne, James P.; Ginsberg, Abigail B.; Laugero, Kevin D.; la Fleur, Susanne E.; Houshyar, Hani; Gomez, Francisca; Bhargava, Aditi; Akana, Susan F.

    2006-01-01

    The hypothalamo-pituitary-adrenal (HPA) axis is the critical mediator of the vertebrate stress response system, responding to environmental stressors by maintaining internal homeostasis and coupling the needs of the body to the wants of the mind. The HPA axis has numerous complex drivers and highly

  17. Beyond the HPA axis: progesterone-derived neuroactive steroids in human stress and emotion

    Directory of Open Access Journals (Sweden)

    Michelle eWirth

    2011-08-01

    Full Text Available Stress and social isolation are well-known risk factors for psychopathology. However, more research is needed as to the physiological mechanisms by which social support buffers the impacts of stress. Research in animal models suggests important roles for progesterone (P and its product, the neuroactive steroid allopregnanolone (ALLO, in stress and psychopathology. These hormones are produced in brain and periphery during stress in rodents, and down-regulate anxiety behavior and HPA axis activity. Human clinical populations, including depressed patients, have alterations in ALLO levels, but it is unclear whether these basal hormone level differences have clinical import. To begin to address this question, this review examines the role of P and ALLO in stress physiology, and the impact of these hormones on mood, in healthy humans. Evidence largely supports that P and ALLO increase during stress in humans. However, P/ALLO administration appears to cause only mild effects on mood and subjective anxiety, while exerting effects consistent with GABA receptor modulation. Additionally, P is linked to motivation for affiliation / social contact; P (and ALLO release may be especially responsive to social rejection. These observations lead to the novel hypothesis that stress-related P/ALLO production functions not only to down-regulate stress and anxiety, but also to promote social contact as a long-term coping strategy. Malfunctioning of the P/ALLO system could therefore underlie depression partly by decreasing propensity to affiliate with others.

  18. Update on stress and depression: the role of the hypothalamic-pituitary-adrenal (HPA axis

    Directory of Open Access Journals (Sweden)

    Mello Andrea de Abreu Feijó de

    2003-01-01

    Full Text Available Over the past 50 years, relationships between stress and the neurobiological changes seen in psychiatric disorders have been well-documented. A major focus of investigations in this area has been the role of the hypothalamic-pituitary-adrenal (HPA axis, both as a marker of stress response and as a mediator of additional downstream pathophysiologic changes. This review examines the emerging literature concerning the relationship between stress, HPA axis function, and depression, as well as the role of early life stress as an important risk factor for HPA axis dysregulation. The more recent studies reviewed suggest that the prominence of HPA axis hyperactivity in adults with depressive and anxiety disorders may constitute a link between the occurrence of adversity in childhood and the development of adult psychopathology

  19. Environmental stressors and epigenetic control of the hypothalamic-pituitary-adrenal-axis (HPA-axis)

    OpenAIRE

    Lee, Richard; Sawa, Akira

    2014-01-01

    In this review, we provide a brief summary of several key studies that broaden our understanding of stress and its epigenetic control of the hypothalamic-pituitary-adrenal axis (HPA)-axis function and behavior. Clinical and animal studies suggest a link among exposure to stress, dysregulation of the HPA-axis, and susceptibility to neuropsychiatric illnesses. Recent studies have supported the notion that exposure to glucocorticoids and stress in various forms, duration, and intensity during di...

  20. HPA axis hyperactivity and attempted suicide in young adult mood disorder inpatients.

    Science.gov (United States)

    Jokinen, Jussi; Nordström, Peter

    2009-07-01

    Hyperactivity of the Hypothalamic-Pituitary-Adrenal (HPA) axis is a consistent finding in Major Depressive Disorder (MDD) and most prospective studies of HPA-axis function have found that non-suppressors in the dexamethasone suppression test (DST) are more likely to commit suicide during follow-up. The results of studies on HPA-axis function and attempted suicide are less consistent. Suicide attempts are more common among young people than the elderly, whereas suicide is more common among the elderly. The impact of age related changes in HPA-axis system activity in relation to suicidal behaviour across the lifecycle may be of importance. The aim of the present study was to investigate the DST results in 36 young adult (30 years or younger) inpatients with mood disorder, with (n=18) and without suicide attempt at the index episode. The DST non-suppressor rate was 25% among young mood disorder inpatients. DST non-suppression was associated with suicide attempt and post-dexamethasone serum cortisol at 11:00 p.m. was significantly higher in suicide attempters compared to non-attempters. The DST non-suppressor rate was 39% in young adult suicide attempters compared with 11% in non-attempters. The results add to previous evidence in support of the role of HPA axis hyperactivity and suicidal behaviour. The present findings motivate to include HPA axis measures in the assessment of depression in young adults.

  1. The different roles of glucocorticoids in the hippocampus and hypothalamus in chronic stress-induced HPA axis hyperactivity.

    Directory of Open Access Journals (Sweden)

    Li-Juan Zhu

    Full Text Available Hypothalamus-pituitary-adrenal (HPA hyperactivity is observed in many patients suffering from depression and the mechanism underling the dysfunction of HPA axis is not well understood. Chronic stress has a causal relationship with the hyperactivity of HPA axis. Stress induces the over-synthesis of glucocorticoids, which will arrive at all the body containing the brain. It is still complicated whether glucocorticoids account for chronic stress-induced HPA axis hyperactivity and in which part of the brain the glucocorticoids account for chronic stress-induced HPA axis hyperactivity. Here, we demonstrated that glucocorticoids were indispensable and sufficient for chronic stress-induced hyperactivity of HPA axis. Although acute glucocorticoids elevation in the hippocampus and hypothalamus exerted a negative regulation of HPA axis, we found that chronic glucocorticoids elevation in the hippocampus but not in the hypothalamus accounted for chronic stress-induced hyperactivity of HPA axis. Chronic glucocorticoids exposure in the hypothalamus still exerted a negative regulation of HPA axis activity. More importantly, we found mineralocorticoid receptor (MR - neuronal nitric oxide synthesis enzyme (nNOS - nitric oxide (NO pathway mediated the different roles of glucocorticoids in the hippocampus and hypothalamus in regulating HPA axis activity. This study suggests that the glucocorticoids in the hippocampus play an important role in the development of HPA axis hyperactivity and the glucocorticoids in the hypothalamus can't induce hyperactivity of HPA axis, revealing new insights into understanding the mechanism of depression.

  2. Mechanisms of Imidacloprid-Induced Alteration of Hypothalamic-Pituitary-Adrenal (HPA Axis after Subchronic Exposure in Male Rats

    Directory of Open Access Journals (Sweden)

    Alya Annabi

    2015-11-01

    Full Text Available Imidacloprid (IMI is known to target the nicotinic acetylcholine receptors (nAChRs in insects, and potentially in mammals. However, IMI toxicity on mammalian tissues has not been adequately evaluated. The aim of the present study was to examine whether IMI induced functional impairment in hypthalamic-pituitary-adrenal (HPA axis tissues. An oral exposure of 40 mg IMI/kg for 28 days in male rats caused a significant increase in malondialdehyde (MDA level. The antioxidant catalase, superoxide dismutase, and glutathione S-transferase showed various alterations following administration, but a significantly depleted thiol (SH groups was only recorded in hypothalamic tissues. The increase in the relative weight of adrenal glands and the increased adrenal cholesterol and plasma adrenocorticotropic hormone (ACTH levels are indicative of general adaptation syndrome. The hypothalamic and pituitary acetylcholinesterase activity and calcium level were significantly increased, highlighting the alteration of cholinergic transmission. In conclusion, the findings obtained show that chronic exposure to IMI may alter biochemical processes of HPA axis.

  3. HPA axis hyperactivity as suicide predictor in elderly mood disorder inpatients.

    Science.gov (United States)

    Jokinen, Jussi; Nordström, Peter

    2008-11-01

    Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis function is associated with suicidal behaviour and age-associated alterations in HPA axis functioning may render elderly individuals more susceptible to HPA dysregulation related to mood disorders. Research on HPA axis function in suicide prediction in elderly mood disorder patients is sparse. The study sample consisted of 99 depressed elderly inpatients 65 years of age or older admitted to the department of Psychiatry at the Karolinska University Hospital between 1980 and 2000. The hypothesis was that elderly mood disorder inpatients who fail to suppress cortisol in the dexamethasone suppression test (DST) are at higher risk of suicide. The DST non-suppression distinguished between suicides and survivors in elderly depressed inpatients and the suicide attempt at the index episode was a strong predictor for suicide. Additionally, the DST non-suppression showed higher specificity and predictive value in the suicide attempter group. Due to age-associated alterations in HPA axis functioning, the optimal cut-off for DST non-suppression in suicide prediction may be higher in elderly mood disorder inpatients. These data demonstrate the importance of attempted suicide and DST non-suppression as predictors of suicide risk in late-life depression and suggest the use for neuroendocrine testing of HPA axis functioning as a complementary tool in suicide prevention.

  4. Association between Mastication, the Hippocampus, and the HPA Axis: A Comprehensive Review.

    Science.gov (United States)

    Azuma, Kagaku; Zhou, Qian; Niwa, Masami; Kubo, Kin-Ya

    2017-08-03

    Mastication is mainly involved in food intake and nutrient digestion with the aid of teeth. Mastication is also important for preserving and promoting general health, including hippocampus-dependent cognition. Both animal and human studies indicate that mastication influences hippocampal functions through the end product of the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoid (GC). Epidemiologic studies suggest that masticatory dysfunction in aged individuals, such as that resulting from tooth loss and periodontitis, acting as a source of chronic stress, activates the HPA axis, leading to increases in circulating GCs and eventually inducing various physical and psychological diseases, such as cognitive impairment, cardiovascular disorders, and osteoporosis. Recent studies demonstrated that masticatory stimulation or chewing during stressful conditions suppresses the hyperactivity of the HPA axis via GCs and GC receptors within the hippocampus, and ameliorates chronic stress-induced hippocampus-dependent cognitive deficits. Here, we provide a comprehensive overview of current research regarding the association between mastication, the hippocampus, and HPA axis activity. We also discuss several potential molecular mechanisms involved in the interactions between mastication, hippocampal function, and HPA axis activity.

  5. Modulation of HPA axis response to social stress in schizophrenia by childhood trauma.

    Science.gov (United States)

    Lange, Claudia; Huber, Christian G; Fröhlich, Daniela; Borgwardt, Stefan; Lang, Undine E; Walter, Marc

    2017-08-01

    HPA axis functioning plays an important role in the etiology of schizophrenia spectrum disorders (SSD). However, only few studies have examined HPA axis responsivity to psychosocial stress in SSD, and results are heterogeneous. Furthermore, childhood trauma is known to influence psychopathology and treatment outcome in SSD, but studies on the influence of childhood trauma on stress related HPA axis activity are missing. The purpose of this study was to investigate cortisol response to a psychosocial stress challenge in SSD patients, and to examine its association with severity of childhood trauma. The present study included 25 subacutely ill patients with a current episode of a chronic SSD and 25 healthy controls. Participants underwent the modified Trier Social Stress Test, and salivary cortisol levels were assessed. The childhood trauma questionnaire was used to assess severity of adverse life events. Overall, cortisol response was blunted in the patient group compared to the control group (pchildhood trauma experience: responders had experienced more emotional abuse in their past (pchildhood trauma might influence stress-related HPA axis activity in SSD. Our data contribute to the hypothesis that severity of childhood trauma may be of pathophysiological relevance in schizophrenia. In addition, it may be an overlooked factor contributing to inconsistent findings regarding HPA axis response to psychosocial stress in SSD. Copyright © 2017. Published by Elsevier Ltd.

  6. Circadian rhythms in the hypothalamo-pituitary-adrenal (HPA) axis

    NARCIS (Netherlands)

    Kalsbeek, A.; van der Spek, R.; Lei, J.; Endert, E.; Buijs, R. M.; Fliers, E.

    2012-01-01

    The pronounced daily variation in the release of adrenal hormones has been at the heart of the deciphering and understanding of the circadian timing system. Indeed, the first demonstration of an endocrine day/night rhythm was provided by Pincus (1943), by showing a daily pattern of 17-keto-steroid

  7. Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)###

    Science.gov (United States)

    While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral functions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone...

  8. Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)

    Science.gov (United States)

    While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral fimctions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone...

  9. In Search of HPA Axis Dysregulation in Child and Adolescent Depression

    Science.gov (United States)

    Guerry, John D.; Hastings, Paul D.

    2011-01-01

    Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in adults with major depressive disorder is among the most consistent and robust biological findings in psychiatry. Given the importance of the adolescent transition to the development and recurrence of depressive phenomena over the lifespan, it is important to have an integrative…

  10. Evidence for Stress-like Alterations in the HPA-Axis in Women Taking Oral Contraceptives

    DEFF Research Database (Denmark)

    Hertel, Johannes; König, Johanna; Homuth, Georg

    2017-01-01

    Using oral contraceptives has been implicated in the aetiology of stress-related disorders like depression. Here, we followed the hypothesis that oral contraceptives deregulate the HPA-axis by elevating circulating cortisol levels. We report for a sample of 233 pre-menopausal women increased...

  11. The effects of stress on hypothalamic-pituitary-adrenal (HPA) axis function in subjects with schizophrenia

    NARCIS (Netherlands)

    P.C. Guest (Paul); D. Martins-de-Souza (Daniel); H. Rahmoune (Hassan); S. Bahn (Sabine); P.C. Guest (Paul)

    2013-01-01

    textabstractOver the last few decades, evidence has been emerging that the pathogenesis of psychiatric disorders such as schizophrenia can involve perturbations of the hypothalamic-pituitary-adrenal (HPA) axis. Variations in the manifestation of these effects could be related to the differences in

  12. The role of BDNF and HPA axis in the neurobiology of burnout syndrome.

    Science.gov (United States)

    Onen Sertoz, Ozen; Tolga Binbay, Ibrahim; Koylu, Ersin; Noyan, Aysin; Yildirim, Emre; Elbi Mete, Hayriye

    2008-08-01

    Chronic stress is known to affect the HPA axis. The few clinical studies which have been conducted on HPA-axis function in burnout have produced inconsistent results. The etiological relationship between sBDNF and burnout has not yet been studied. The aim of the current study was to investigate the role of BDNF and HPA axis in the neurobiology of burnout. In the current study 37 clinically diagnosed burnout participants were compared with 35 healthy controls in terms of BDNF, HPA axis, burnout symptoms, depression, anxiety and psychosomatic complaints. Basal serum cortisol, sBDNF and cortisol level after 1 mg DST was sampled. We found no significant differences in terms of HPA-axis function (for basal serum cortisol, p=0.592; for cortisol level after 1 mg DST, p=0.921), but we did find lowered sBDNF levels in burnout group (88.66+/-18.15 pg/ml) as compared to healthy controls (102.18+/-20.92 pg/ml) and the difference was statistically significant (p=0.005). Logistic Regression Analysis revealed that emotional exhaustion (p=0.05), depersonalization (p=0.005) and depression (p=0.025) were significantly associated with burnout. sBDNF levels correlated negatively with emotional exhaustion (r=-,268, p=0.026), depersonalization (r=-,333, p=0.005) and correlated positively with competence (r=0.293, p=0.015) sub-scales of burnout inventory. However, there were no significant relationships between cortisol levels and sBDNF levels (r=0.80, p=0.51), depression, anxiety, psychosomatic complaints and burnout inventory. Our results suggest that low BDNF might contribute to the neurobiology of burnout syndrome and it seems to be associated with burnout symptoms including altered mood and cognitive functions.

  13. Long-term effects of early parental loss due to divorce on the HPA axis.

    Science.gov (United States)

    Bloch, Miki; Peleg, Ido; Koren, Danny; Aner, Hamotal; Klein, Ehud

    2007-04-01

    We investigated the long-term effects of divorce and early separation from one parent on HPA axis reactivity, in young adults without psychopathology. Participants were 44 young subjects, 22 whose parents divorced before they reached age 10, and 22 controls. Psychiatric symptomatology was measured with the Brief Symptom Inventory (BSI), family perceived stress by the Dyadic Adjustment Scale (DAS), and bonding by the Parental Bonding Instrument (PBI). Assessment of HPA axis function included baseline morning cortisol and ACTH and cortisol response to a CRH stimulation test. No baseline or stimulated group differences were observed for ACTH. Cortisol levels were consistently but insignificantly lower in the divorce group throughout the CRH stimulation reaching statistical significance only at 5 min (p<0.03). Group by time effect reached a trend level (p<0.06). A correlation was found between psychiatric symptomatology and PBI scores; however, both parameters did not correlate with HPA axis activity. A significant correlation was found between DAS scores and ACTH. A regression model revealed a contributing effect for both family stress and child-parent bonding to stimulated ACTH levels. These preliminary findings suggest that even in the absence of adult psychopathology, a history of childhood separation from one parent due to divorce may lead to detectable, albeit mild, long-term alterations in HPA axis activity. Furthermore, they suggest that level of stress at home and parental bonding are important determinants of this effect. It is likely that divorce has significant and sustained effects on children's HPA axis only in the context of a traumatic separation.

  14. Stress-induced oxytocin release and oxytocin cell number and size in prepubertal and adult male and female rats.

    Science.gov (United States)

    Minhas, Sumeet; Liu, Clarissa; Galdamez, Josselyn; So, Veronica M; Romeo, Russell D

    2016-08-01

    Studies indicate that adolescent exposure to stress is a potent environmental factor that contributes to psychological and physiological disorders, though the mechanisms that mediate these dysfunctions are not well understood. Periadolescent animals display greater stress-induced hypothalamic-pituitary-adrenal (HPA) axis responses than adults, which may contribute to these vulnerabilities. In addition to the HPA axis, the hypothalamo-neurohypophyseal tract (HNT) is also activated in response to stress. In adults, stress activates this system resulting in secretion of oxytocin from neurons in the supraoptic (SON) and paraventricular (PVN) nuclei. However, it is currently unknown whether a similar or different response occurs in prepubertal animals. Given the influence of these hormones on a variety of emotional behaviors and physiological systems known to change as an animal transitions into adulthood, we investigated stress-induced HPA and HNT hormonal responses before and after stress, as well as the number and size of oxytocin-containing cells in the SON and PVN of prepubertal (30d) and adult (70d) male and female rats. Though we found the well-established protracted adrenocorticotropic hormone and corticosterone response in prepubertal males and females, only adult males and prepubertal females showed a significant stress-induced increase in plasma oxytocin levels. Moreover, though we found no pubertal changes in the number of oxytocin cells, we did find a pubertal-related increase in oxytocin somal size in both the SON and PVN of males and females. Taken together, these data indicate that neuroendocrine systems can show different patterns of stress reactivity before and after adolescent development and that these responses can be further modified by sex. Given the impact of these hormones on a variety of systems, it will be imperative to further explore these changes in hormonal stress reactivity and their role in adolescent health. Copyright © 2016 Elsevier

  15. Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Gordijn, Maartje S.; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

    2012-01-01

    Background Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses may cause suppression of the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress

  16. Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Gordijn, Maartje S.; Rensen, Niki; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

    2015-01-01

    Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate

  17. Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Rensen, Niki; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

    2017-01-01

    Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate

  18. Dysregulation of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages: An individual participant meta-analysis

    NARCIS (Netherlands)

    Gardner, M.P.; Lightman, S.; Sayer, A.A.; Cooper, C.; Cooper, R.; Deeg, D.J.H.; Ebrahim, S.; Gallacher, J.; Kivimaki, M.; Kumari, M.; Kuh, D; Martin, R.M.; Peeters, G.; Ben-Shlomoa, Y.

    2013-01-01

    The association between functioning of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages remains poorly understood. We carried out meta-analyses to test the hypothesis that dysregulation of the HPA axis, as indexed by patterns of diurnal cortisol release, is

  19. Associations between HPA axis functioning and level of anxiety in children and adolescents with an anxiety disorder

    NARCIS (Netherlands)

    Kallen, V. L.; Tulen, J. H. M.; Utens, E. M. W. J.; Treffers, P. D. A.; de Jong, F. H.; Ferdinand, R. F.

    2008-01-01

    The hypothalamus-pituitary-adrenal (HPA) axis becomes active in response to stress. Hence, increased levels of anxiety in children and adolescents may be associated with changes in HPA-axis functioning. The aim of this study was to test if level of anxiety or specific anxiety disorders were

  20. Cognition and HPA axis reactivity in mildly to moderately depressed outpatients

    DEFF Research Database (Denmark)

    Krogh, Jesper; Videbech, Poul; Renvillard, Signe Groth

    2012-01-01

    Background: Patients with depression display neurobiological changes of the hypothalamic-pituitary axis as well as cognitive disturbances. Aims: To assess any association between hypothalamus-pituitary-adrenal (HPA) axis reactivity and memory-related cognitive functions. Methods: Depressed...... the following day at the same times. Results: Patients and controls did not differ on any memory-related cognitive skills. After dexamethasone the cortisol level was 1.7 nmol/l higher (95% CI 0.0-2.8, P =¿0.05) in depressed patients compared with controls. In the control group, but not in the patients...... after dexamethasone and visuo-spatial memory primarily driven by the healthy controls. Otherwise, no association were found between HPA axis reactivity and memory-related cognitive function....

  1. Daily family stress and HPA axis functioning during adolescence: The moderating role of sleep

    Science.gov (United States)

    Chiang, Jessica J.; Tsai, Kim M.; Park, Heejung; Bower, Julienne E.; Almeida, David M.; Dahl, Ronald E.; Irwin, Michael R.; Seeman, Teresa E.; Fuligni, Andrew J.

    2017-01-01

    The present study examined the moderating role of sleep in the association between family demands and conflict and hypothalamic-pituitary-adrenal (HPA) axis functioning in a sample of ethnically diverse adolescents (n = 316). Adolescents completed daily diary reports of family demands and conflict for 15 days, and wore actigraph watches during the first 8 nights to assess sleep. Participants also provided five saliva samples for 3 consecutive days to assess diurnal cortisol rhythms. Regression analyses indicated that sleep latency and efficiency moderated the link between family demands and the cortisol awakening response. Specifically, family demands were related to a smaller cortisol awakening response only among adolescents with longer sleep latency and lower sleep efficiency. These results suggest that certain aspects of HPA axis functioning may be sensitive to family demands primarily in the context of longer sleep latency and lower sleep efficiency. PMID:27235639

  2. Interaction Between 5-HTTLPR and BDNF Val66Met Polymorphisms on HPA Axis Reactivity in Preschoolers

    OpenAIRE

    Dougherty, Lea R.; Klein, Daniel N.; Congdon, Eliza; Canli, Turhan; Hayden, Elizabeth P.

    2009-01-01

    This study examined whether the interaction between the serotonin transporter promoter region (5-HTTLPR) and brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms was associated with hypothalamic-pituitary-adrenal (HPA) axis reactivity to stress. A community sample of 144 preschool-aged children was genotyped and exposed to stress-inducing laboratory tasks. Salivary cortisol was obtained at four time points during a standardized laboratory assessment before and after stressors invol...

  3. Early life stress, HPA axis adaptation and mechanisms contributing to later health outcomes

    Directory of Open Access Journals (Sweden)

    Jayanthi eManiam

    2014-05-01

    Full Text Available Stress activates the hypothalamic-pituitary-adrenal (HPA axis, which then modulates the degree of adaptation and response to a later stressor. It is known that early life stress can impact on later health but less is known about how early life stress impairs HPA axis activity, contributing to maladaptation of the stress response system. Early life stress exposure (either prenatally or in the early postnatal period can impact developmental pathways resulting in lasting structural and regulatory changes that predispose to adulthood disease. Epidemiological, clinical and experimental studies have demonstrated that early life stress produces long-term hyper responsiveness to stress with exaggerated circulating glucocorticoids, and enhanced anxiety and depression-like behaviours. Recently, evidence has emerged on early life stress induced metabolic derangements, for example hyperinsulinemia and altered insulin sensitivity on exposure to a high energy diet later in life. This draws our attention to the contribution of later environment to disease vulnerability. Early life stress can alter the expression of genes in peripheral tissues, such as the glucocorticoid receptor and 11-beta hydroxysteroid dehydrogenase (11β-HSD1. We propose that interactions between altered HPA axis activity and liver 11β-HSD1 modulates both tissue and circulating glucocorticoid availability, with adverse metabolic consequences. This review discusses the potential mechanisms underlying early life stress induced maladaptation of the HPA axis, and its subsequent effects on energy utilisation and expenditure. The effects of positive later environments as a means of ameliorating early life stress induced health deficits, and proposed mechanisms underpinning the interaction between early life stress and subsequent detrimental environmental exposures on metabolic risk will be outlined. Limitations in current methodology linking early life stress and later health outcomes will also

  4. Early-Life Stress, HPA Axis Adaptation, and Mechanisms Contributing to Later Health Outcomes

    Science.gov (United States)

    Maniam, Jayanthi; Antoniadis, Christopher; Morris, Margaret J.

    2014-01-01

    Stress activates the hypothalamic–pituitary–adrenal (HPA) axis, which then modulates the degree of adaptation and response to a later stressor. It is known that early-life stress can impact on later health but less is known about how early-life stress impairs HPA axis activity, contributing to maladaptation of the stress–response system. Early-life stress exposure (either prenatally or in the early postnatal period) can impact developmental pathways resulting in lasting structural and regulatory changes that predispose to adulthood disease. Epidemiological, clinical, and experimental studies have demonstrated that early-life stress produces long term hyper-responsiveness to stress with exaggerated circulating glucocorticoids, and enhanced anxiety and depression-like behaviors. Recently, evidence has emerged on early-life stress-induced metabolic derangements, for example hyperinsulinemia and altered insulin sensitivity on exposure to a high energy diet later in life. This draws our attention to the contribution of later environment to disease vulnerability. Early-life stress can alter the expression of genes in peripheral tissues, such as the glucocorticoid receptor and 11-beta hydroxysteroid dehydrogenase (11β-HSD1). We propose that interactions between altered HPA axis activity and liver 11β-HSD1 modulates both tissue and circulating glucocorticoid availability, with adverse metabolic consequences. This review discusses the potential mechanisms underlying early-life stress-induced maladaptation of the HPA axis, and its subsequent effects on energy utilization and expenditure. The effects of positive later environments as a means of ameliorating early-life stress-induced health deficits, and proposed mechanisms underpinning the interaction between early-life stress and subsequent detrimental environmental exposures on metabolic risk will be outlined. Limitations in current methodology linking early-life stress and later health outcomes will also be

  5. Burnout Is Associated with Reduced Parasympathetic Activity and Reduced HPA Axis Responsiveness, Predominantly in Males

    Directory of Open Access Journals (Sweden)

    Wieke de Vente

    2015-01-01

    Full Text Available There is mounting evidence that burnout is a risk factor for cardiovascular disease (CVD. Stress-related dysregulation of the sympathetic and parasympathetic system and the hypothalamic pituitary adrenal (HPA axis may explain the enhanced risk for CVD. To test this hypothesis, 55 patients (34 males and 21 females with burnout on sickness absence and 40 healthy participants (16 males and 24 females were exposed to a psychosocial stressor consisting of mental arithmetic and public speech. Physiological variables (i.e., blood pressure, heart rate, cardiac output, vascular resistance, cortisol, and alpha-amylase were measured. Basal levels, reactivity, and recovery were compared between groups. In male patients, baseline systolic blood pressure was higher, whereas basal alpha-amylase and cortisol reactivity were lower than in healthy males. In female patients, a tendency for lower basal cortisol was found as compared to healthy females. Furthermore, reduced basal heart rate variability and a trend for elevated basal cardiac output were observed in both male and female patients. Burnout is characterised by dysregulation of the sympathetic and parasympathetic system and the HPA axis, which was more pronounced in males than in females. This study further supports burnout as being a risk factor for CVD through dysregulation of the sympathetic and parasympathetic system and the HPA axis.

  6. Sex hormones and oxytocin augmentation strategies in schizophrenia : A quantitative review

    NARCIS (Netherlands)

    Heringa, Sophie M; Begemann, Marieke J H; Goverde, Angelique J; Sommer, Iris E C

    2015-01-01

    INTRODUCTION: Sex differences in incidence, onset and course of schizophrenia suggest sex hormones play a protective role in the pathophysiology. Such a role is also proposed for oxytocin, another important regulator of reproduction function. Evidence on the efficacy of sex hormones and oxytocin in

  7. Recovery of HPA Axis Function After Successful Gonadotropin-Induced Pregnancy and Delivery in a Woman With Panhypopituitarism: Case Report and Review.

    Science.gov (United States)

    Wang, Yi; Zhang, Qiongyue; Yang, Jianzhi; Zhao, Xiaolong; He, Min; Shou, Xuefei; Li, Shiqi; Li, Yiming; Wang, Yongfei; Ye, Hongying

    2015-09-01

    Hypopituitarism is defined as the partial or complete defect of anterior pituitary hormone secretion. Patients with hypopituitarism usually need life-long hormone replacement therapy. However, in this case, we report a patient with panhypopituitarism whose hypothalamus-pituitary-adrenal (HPA) axis function was completely recovered after pregnancy and delivery. In this case study, we reported the case management and conducted a review of literature to identify the possible mechanism of pituitary function recovery. The patient who suffered from secondary amenorrhea was found a nonfunctioning pituitary macroadenoma, and the hormone test showed serum cortisol, FT3, FT4, thyrotropic hormone, and prolactin were at normal range. After surgical removal of the tumor which invasion in the sellar region, the patient had panhypopituitarism confirmed by the routine hormone test. Though spontaneous pregnancy is impossible in female patients with panhypopituitarism, the patient was restored fertility by the help of artificial reproductive techniques. After the confirmation of the pregnancy, levothyroixine was increased to 75 μg daily and readjusted to 150 μg daily before delivery according to the monthly measurement thyroid function. Hydrocortisone 10 mg daily replaced cortisone acetate; the dose was increased according to the symptoms of morning sickness. A single stress dose of hydrocortisone (200 mg) was used before elective cesarean delivery and was tapered to the dose of 10 mg per day in 1 week. Levothyroixine was reduced to 75 μg daily after delivery. During follow-up, her hypothalamus-pituitary-adrenal (HPA) axis function was completely recovered. The peak serum cortisol level could increase to 19.08 μg/dL by insulin-induced hypoglycemia. However, growth hormone remained unresponsive to the insulin-tolerance test, and thyroid hormone still needed exogenous supplementation. Hormone replacement therapy needed closely followed by endocrinologist and multidisciplinary

  8. Effects of Early-Life Adversity on Hippocampal Structures and Associated HPA Axis Functions.

    Science.gov (United States)

    Dahmen, Brigitte; Puetz, Vanessa B; Scharke, Wolfgang; von Polier, Georg G; Herpertz-Dahlmann, Beate; Konrad, Kerstin

    2018-01-01

    Early-life adversity (ELA) is one of the major risk factors for serious mental and physical health risks later in life. ELA has been associated with dysfunctional neurodevelopment, especially in brain structures such as the hippocampus, and with dysfunction of the stress system, including the hypothalamic-pituitary-adrenal (HPA) axis. Children who have experienced ELA are also more likely to suffer from mental health disorders such as depression later in life. The exact interplay of aberrant neurodevelopment and HPA axis dysfunction as risks for psychopathology is not yet clear. We investigated volume differences in the bilateral hippocampus and in stress-sensitive hippocampal subfields, behavior problems, and diurnal cortisol activity in 24 children who had experienced documented ELA (including out-of-home placement) in a circumscribed duration of adversity only in their first 3 years of life in comparison to data on 25 control children raised by their biological parents. Hippocampal volumes and stress-sensitive hippocampal subfields (Cornu ammonis [CA]1, CA3, and the granule-cell layer of the dentate gyrus [GCL-DG]) were significantly smaller in children who had experienced ELA, taking psychiatric diagnoses and dimensional psychopathological symptoms into account. ELA moderated the relationship between left hippocampal volume and cortisol: in the control group, hippocampal volumes were not related to diurnal cortisol, while in ELA children, a positive linear relationship between left hippocampal volume and diurnal cortisol was present. Our findings show that ELA is associated with altered development of the hippocampus, and an altered relationship between hippocampal volume and HPA axis activity in youth in care, even after they have lived in stable and caring foster family environments for years. Altered hippocampal development after ELA could thus be associated with a risk phenotype for the development of psychiatric disorders later in life. © 2017 S. Karger

  9. Progressive dysregulation of autonomic and HPA axis functions in HIV-1 clade C infection in South India.

    Science.gov (United States)

    Chittiprol, Seetharamaiah; Kumar, Adarsh M; Satishchandra, P; Taranath Shetty, K; Bhimasena Rao, R S; Subbakrishna, D K; Philip, Mariyamma; Satish, K S; Ravi Kumar, H; Kumar, Mahendra

    2008-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection causes a wide spectrum of abnormalities in neurological, neuropsychological, and neuroendocrinological functions. Several studies report disturbance in autonomic nervous system (ANS) and hypothalamic pituitary-adrenal (HPA) axis function in HIV-1B infected individuals. However, no such investigations on the effect of HIV-1 clade C infection, particularly during the initial phase of the disease progression, have been reported. The present investigations were carried out longitudinally over a 2-year period at 12 monthly intervals in clinically asymptomatic HIV-1 clade C seropositive patients (n=120) and seronegative control subjects (n=29). We determined both the basal levels and the dynamic changes in plasma levels of norepinephrine (NE), epinephrine (E), adrenocorticotrophic hormone (ACTH) and cortisol (CORT). Studies were also extended longitudinally (at three separate yearly visits of each participant), to evaluate the response of autonomic and HPA axis to mirror star tracing challenge test (MSTCT) and the values were determined as area under the curve (AUC, corrected for baseline levels of NE, E, ACTH, and CORT). The findings show that the values of basal plasma NE levels, as well as NE response to MSTCT (AUC) at the first visit of HIV-1 seropositive individuals did not differ from those found in the control subjects (NE, pg/ml, HIV-1C=313.5+/-12.7 vs. controls=353.0+/-21.3; p=NS; AUC, HIV-1C=225+/-14.75 vs. controls=232.7+/-19.34; p=NS, respectively). At the subsequent two visits of HIV-1 positive patients however, NE response to MSTCT challenge was progressively attenuated (AUC=235+/-19.5 and 162.7+/-13.6; p<0.01 and 0.05, respectively) compared to that found at the first visit. On the other hand, plasma levels of E as well as E response to MSTCT at the first visit were significantly lower in HIV-1C seropositive individuals compared to those in the control subjects (pg/ml, HIV-1C=77.30+/-5.7 vs. controls

  10. Microbial symbionts accelerate wound healing via the neuropeptide hormone oxytocin.

    Directory of Open Access Journals (Sweden)

    Theofilos Poutahidis

    Full Text Available Wound healing capability is inextricably linked with diverse aspects of physical fitness ranging from recovery after minor injuries and surgery to diabetes and some types of cancer. Impact of the microbiome upon the mammalian wound healing process is poorly understood. We discover that supplementing the gut microbiome with lactic acid microbes in drinking water accelerates the wound-healing process to occur in half the time required for matched control animals. Further, we find that Lactobacillus reuteri enhances wound-healing properties through up-regulation of the neuropeptide hormone oxytocin, a factor integral in social bonding and reproduction, by a vagus nerve-mediated pathway. Bacteria-triggered oxytocin serves to activate host CD4+Foxp3+CD25+ immune T regulatory cells conveying transplantable wound healing capacity to naive Rag2-deficient animals. This study determined oxytocin to be a novel component of a multi-directional gut microbe-brain-immune axis, with wound-healing capability as a previously unrecognized output of this axis. We also provide experimental evidence to support long-standing medical traditions associating diet, social practices, and the immune system with efficient recovery after injury, sustained good health, and longevity.

  11. Metabotropic glutamate receptor subtype 7 ablation causes dysregulation of the HPA axis and increases hippocampal BDNF protein levels: implications for stress-related psychiatric disorders.

    Science.gov (United States)

    Mitsukawa, Kayo; Mombereau, Cedric; Lötscher, Erika; Uzunov, Doncho P; van der Putten, Herman; Flor, Peter J; Cryan, John F

    2006-06-01

    Regulation of neurotransmission via group-III metabotropic glutamate receptors (mGluR4, -6, -7, and -8) has recently been implicated in the pathophysiology of affective disorders, such as major depression and anxiety. For instance, mice with a targeted deletion of the gene for mGluR7 (mGluR7-/-) showed antidepressant and anxiolytic-like effects in a variety of stress-related paradigms, including the forced swim stress and the stress-induced hyperthermia tests. Deletion of mGluR7 reduces also amygdala- and hippocampus-dependent conditioned fear and aversion responses. Since the hypothalamic-pituitary-adrenal (HPA) axis regulates the stress response we investigate whether parameters of the HPA axis at the levels of selected mRNA transcripts and endocrine hormones are altered in mGluR7-deficient mice. Over all, mGluR7-/- mice showed only moderately lower serum levels of corticosterone and ACTH compared with mGluR7+/+ mice. More strikingly however, we found strong evidence for upregulated glucocorticoid receptor (GR)-dependent feedback suppression of the HPA axis in mice with mGluR7 deficiency: (i) mRNA transcripts of GR were significantly upregulated in the hippocampus of mGluR7-/- animals, (ii) similar increases were seen with 5-HT1A receptor transcripts, which are thought to be directly controlled by the transcription factor GR and finally (iii) mGluR7-/- mice showed elevated sensitivity to dexamethasone-induced suppression of serum corticosterone when compared with mGluR7+/+ animals. These results indicate that mGluR7 deficiency causes dysregulation of HPA axis parameters, which may account, at least in part, for the phenotype of mGluR7-/- mice in animal models for anxiety and depression. In addition, we present evidence that protein levels of brain-derived neurotrophic factor are also elevated in the hippocampus of mGluR7-/- mice, which we discuss in the context of the antidepressant-like phenotype found in those animals. We conclude that genetic ablation of m

  12. HPA-axis stress reactivity in youth depression: evidence of impaired regulatory processes in depressed boys.

    Science.gov (United States)

    Lopez-Duran, Nestor L; McGinnis, Ellen; Kuhlman, Kate; Geiss, Elisa; Vargas, Ivan; Mayer, Stefanie

    2015-01-01

    Given the link between youth depression and stress exposure, efforts to identify related biomarkers have involved examinations of stress regulation systems, including the hypothalamic-pituitary-adrenal (HPA) axis. Despite these vast efforts, the underlying mechanisms at play, as well as factors that may explain heterogeneity of past findings, are not well understood. In this study, we simultaneously examined separate components of the HPA-axis response (e.g. activation intensity, peak levels, recovery) to the Socially Evaluated Cold-Pressor Test in a targeted sample of 115 youth (age 9-16), recruited to overrepresent youth with elevated symptoms of depression. Among youth who displayed a cortisol response to the task, depression symptoms were associated with higher peak responses but not greater rate of activation or recovery in boys only. Among those who did not respond to the task, depression symptoms were associated with greater cortisol levels throughout the visit in boys and girls. Results suggest that depression symptoms are associated with a more prolonged activation of the axis and impaired recovery to psychosocial stressors primarily in boys. We discussed two potential mechanistic explanations of the link between depression symptoms and the duration of activation: (1) inhibitory shift (i.e. point at which the ratio of inhibitory and excitatory input into the axis shifts from greater excitatory to greater inhibitory input) or (2) inhibitory threshold (i.e. level of cortisol exposure required to activate the axis' feedback inhibition system).

  13. Do different data analytic approaches generate discrepant findings when measuring mother-infant HPA axis attunement?

    Science.gov (United States)

    Bernard, Nicola K; Kashy, Deborah A; Levendosky, Alytia A; Bogat, G Anne; Lonstein, Joseph S

    2017-03-01

    Attunement between mothers and infants in their hypothalamic-pituitary-adrenal (HPA) axis responsiveness to acute stressors is thought to benefit the child's emerging physiological and behavioral self-regulation, as well as their socioemotional development. However, there is no universally accepted definition of attunement in the literature, which appears to have resulted in inconsistent statistical analyses for determining its presence or absence, and contributed to discrepant results. We used a series of data analytic approaches, some previously used in the attunement literature and others not, to evaluate the attunement between 182 women and their 1-year-old infants in their HPA axis responsivity to acute stress. Cortisol was measured in saliva samples taken from mothers and infants before and twice after a naturalistic laboratory stressor (infant arm restraint). The results of the data analytic approaches were mixed, with some analyses suggesting attunement while others did not. The strengths and weaknesses of each statistical approach are discussed, and an analysis using a cross-lagged model that considered both time and interactions between mother and infant appeared the most appropriate. Greater consensus in the field about the conceptualization and analysis of physiological attunement would be valuable in order to advance our understanding of this phenomenon. © 2016 Wiley Periodicals, Inc.

  14. UV irradiation to mouse skin decreases hippocampal neurogenesis and synaptic protein expression via HPA axis activation.

    Science.gov (United States)

    Han, Mira; Ban, Jae-Jun; Bae, Jung-Soo; Shin, Chang-Yup; Lee, Dong Hun; Chung, Jin Ho

    2017-11-14

    The skin senses external environment, including ultraviolet light (UV). Hippocampus is a brain region that is responsible for memory and emotion. However, changes in hippocampus by UV irradiation to the skin have not been studied. In this study, after 2 weeks of UV irradiation to the mouse skin, we examined molecular changes related to cognitive functions in the hippocampus and activation of the hypothalamic-pituitary-adrenal (HPA) axis. UV exposure to the skin decreased doublecortin-positive immature neurons and synaptic proteins, including N-methyl-D-aspartate receptor 2 A and postsynaptic density protein-95, in the hippocampus. Moreover, we observed that UV irradiation to the skin down-regulated brain-derived neurotrophic factor expression and ERK signaling in the hippocampus, which are known to modulate neurogenesis and synaptic plasticity. The cutaneous and central HPA axes were activated by UV, which resulted in significant increases in serum levels of corticosterone. Subsequently, UV irradiation to the skin activated the glucocorticoid-signaling pathway in the hippocampal dentate gyrus. Interestingly, after 6 weeks of UV irradiation, mice showed depression-like behavior in the tail suspension test. Taken together, our data suggest that repeated UV exposure through the skin may negatively affect hippocampal neurogenesis and synaptic plasticity along with HPA axis activation.

  15. Effects of intranasal and peripheral oxytocin or gastrin-releasing peptide administration on social interaction and corticosterone levels in rats.

    Science.gov (United States)

    Kent, Pamela; Awadia, Alisha; Zhao, Leah; Ensan, Donna; Silva, Dinuka; Cayer, Christian; James, Jonathan S; Anisman, Hymie; Merali, Zul

    2016-02-01

    The intranasal route of drug administration has gained increased popularity as it is thought to allow large molecules, such as peptide hormones, more direct access to the brain, while limiting systemic exposure. Several studies have investigated the effects of intranasal oxytocin administration in humans as this peptide is associated with prosocial behavior. There are, however, few preclinical studies investigating the effects of intranasal oxytocin administration in rodents. Oxytocin modulates hypothalamic-pituitary-adrenal (HPA) axis functioning and it has been suggested that oxytocin's ability to increase sociability may occur through a reduction in stress reactivity. Another peptide that appears to influence both social behavior and HPA axis activity is gastrin-releasing peptide (GRP), but it is not known if these GRP-induced effects are related. With this in mind, in the present study, we assessed the effects of intranasal and intraperitoneal oxytocin and GRP administration on social interaction and release of corticosterone in rats. Intranasal and intraperitoneal administration of 20, but not 5 μg, of oxytocin significantly increased social interaction, whereas intranasal and peripheral administration of GRP (20 but not 5 μg) significantly decreased levels of social interaction. In addition, while intranasal oxytocin (20 μg) had no effect on blood corticosterone levels, a marked increase in blood corticosterone levels was observed following intraperitoneal oxytocin administration. With GRP, intranasal (20 μg) but not peripheral administration increased corticosterone levels. These findings provide further evidence that intranasal peptide delivery can induce behavioral alterations in rodents which is consistent with findings from human studies. In addition, the peptide-induced changes in social interaction were not linked to fluctuations in corticosterone levels. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Effects of resistance exercise on the HPA axis response to psychological stress during short-term smoking abstinence in men.

    Science.gov (United States)

    Ho, Jen-Yu; Kraemer, William J; Volek, Jeff S; Vingren, Jakob L; Fragala, Maren S; Flanagan, Shawn D; Maladouangdock, Jesse; Szivak, Tunde K; Hatfield, Disa L; Comstock, Brett A; Dunn-Lewis, Courtenay; Ciccolo, Joseph T; Maresh, Carl M

    2014-03-01

    The purpose of this study was to examine the effects of resistance exercise on the hypothalamic-pituitary-adrenal axis (HPA) response to mental challenge, withdrawal symptoms, urge to smoke, and cognitive stress during 24-hour smoking abstinence. 8 sedentary smokers (mean±SD age: 20.1±1.7y; height: 171.6±10.8cm; body mass: 70.4±12.0kg; smoking history: 2.9±0.8y) completed a 24-hour ad libitum smoking trial (SMO) followed by two 24-hour smoking abstinence trials. During abstinence trials, participants performed six whole body resistance exercises (EX) or a control condition (CON) in the morning, followed by mental challenge tasks in the afternoon. Plasma adrenocorticotropin hormone (ACTH), and salivary and serum cortisol were measured during each visit at rest (REST), and then before (PRE-EX), immediately after (IP-EX), and 30min after exercise (30-EX); and before (PRE-MC), immediately after (IP-MC), and 30min after mental challenge (30-MC). Resistance exercise significantly (p≤0.05) elevated plasma ACTH and serum cortisol at IP-EX during EX compared with SMO and CON trials. Resting ACTH, salivary and serum cortisol concentrations at Pre-MC did not differ between EX and CON trials. The HPA axis response to mental challenge was similar after EX and CON trials. Finally, resistance exercise did not reduce withdrawal symptoms, urge to smoke, or stress. Resistance exercise did not substantially alter resting HPA hormones or the HPA response to mental challenge tasks during 24h of smoking abstinence. © 2013.

  17. HPA-axis hyperactivity and mortality in psychotic depressive disorder: preliminary findings.

    Science.gov (United States)

    Coryell, William; Fiedorowicz, Jess; Zimmerman, Mark; Young, Elizabeth

    2008-06-01

    The excess mortality associated with depressive disorders has been most often attributed to risks for suicide but diverse findings indicate that depressive disorders also increase risks for cardiovascular (CV) mortality. Among the possible mediators is the hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity that characterizes many cases of relatively severe depressive disorder and severity is characteristic of psychotic depressive disorder. The following describes a 17-year mortality follow-up of 54 patients with Research Diagnostic Criteria (RDC) psychotic major depression or schizoaffective, mainly affective, depression. All had baseline assessments that included a 1mg dexamethasone suppression test with post-dexamethasone samples at 8 a.m., 4 p.m. and 11 p.m. Regression analyses showed that both greater age and higher maximum post-dexamethasone cortisol concentrations predicted deaths due to CV causes (t=4.01, pdepressive disorder to CV mortality.

  18. Alterations in HPA-axis and autonomic nervous system functioning in childhood anxiety disorders point to a chronic stress hypothesis.

    Science.gov (United States)

    Dieleman, Gwendolyn C; Huizink, Anja C; Tulen, Joke H M; Utens, Elisabeth M W J; Creemers, Hanneke E; van der Ende, Jan; Verhulst, Frank C

    2015-01-01

    It is of debate whether or not childhood anxiety disorders (AD) can be captured by one taxonomic construct. This study examined whether perceived arousal (PA), autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis measures can distinguish children with different primary diagnoses of clinical anxiety disorders (AD) from each other, and from a general population reference group (GP). The study sample consisted of 152 AD children (comparing separation anxiety disorder, generalized anxiety disorder, social phobia and specific phobia), aged 8- to 12-years, and 200 same-aged reference children. HPA-axis functioning was measured by a diurnal cortisol profile. ANS functioning was measured by continuous measures of skin conductance level in rest and during a mental arithmetic task and high frequency heart rate variability in rest. PA was assessed by a questionnaire. The AD sample showed lower high frequency heart rate variability during rest, heightened anticipatory PA, higher basal and reactive skin conductance levels and lower basal HPA-axis functioning compared to the GP sample. The existence of three or more clinical disorders, i.e. a high clinical 'load', was associated with lower basal HPA-axis functioning, higher skin conductance level and lower posttest PA. Specific phobia could be discerned from social phobia and separation anxiety disorder on higher skin conductance level. Our findings indicated that children with AD have specific psychophysiological characteristics, which resemble the psychophysiological characteristics of chronic stress. A high clinical 'load' is associated with an altered ANS and HPA-axis functioning. Overall, ANS and HPA-axis functioning relate to AD in general, accept for specific phobia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. HPA axis dysregulation, NR3C1 polymorphisms and glucocorticoid receptor isoforms imbalance in metabolic syndrome.

    Science.gov (United States)

    Martins, Clarissa Silva; Elias, Daniel; Colli, Leandro Machado; Couri, Carlos Eduardo; Souza, Manoel Carlos L A; Moreira, Ayrton C; Foss, Milton C; Elias, Lucila L K; de Castro, Margaret

    2017-03-01

    Metabolic syndrome (MetS) shares several similarities with hypercortisolism. To evaluate hypothalamic-pituitary-adrenal (HPA) axis sensitivity to dexamethasone (DEX), NR3C1 single nucleotide polymorphisms (SNPs), and expression of glucocorticoid receptor (GR) isoforms and cytokines in peripheral immune cells of MetS patients and controls. Prospective study with 40 MetS patients and 40 controls was conducted at the Ribeirão Preto Medical School University Hospital. Plasma and salivary cortisol were measured in basal conditions and after 0.25, 0.5, and 1 mg of DEX given at 2300 h. In addition, p.N363S (rs6195), p.ER22/23EK (rs6189-6190), and BclI (rs41423247) SNPs were evaluated by quantitative polymerase chain reaction allelic discrimination. Exons 3 to 9 and exon/intron boundaries of NR3C1 were sequenced. GR isoforms and cytokines (IL1B, IL2, IL4, IL6, IL8, IL10, IFNγ, TNFα) expression were assessed by quantitative polymerase chain reaction. Plasma and salivary cortisol (nmol/L) after 1-mg DEX were higher in MetS patients compared with controls (PF: 70.2 ± 17.3 vs 37.9 ± 2.6, P = .02, and SF: 4.9 ± 1.7 vs 2.2 ± 0.3, P molecular mechanism of glucocorticoid resistance in MetS. Thus, HPA axis dysregulation might contribute to MetS pathogenesis. Copyright © 2016 John Wiley & Sons, Ltd.

  20. The BDNF Val66Met polymorphism affects HPA-axis reactivity to acute stress.

    Science.gov (United States)

    Alexander, Nina; Osinsky, Roman; Schmitz, Anja; Mueller, Eva; Kuepper, Yvonne; Hennig, Juergen

    2010-07-01

    Growing evidence suggests that individual differences in HPA-axis reactivity to psychosocial stress are partly due to heritable influences. However, knowledge about the role of specific genetic variants remains very limited to date. Since brain-derived neurotrophic factor (BDNF) not only exhibits neurotrophic actions but is also involved in the regulation of hypothalamic neuropeptides, we investigated the role of a common functional polymorphism within the BDNF gene (BDNF Val66Met) in the context of endocrine and cardiovascular stress reactivity. Healthy male adults (N=100) were genotyped and exposed to a standardized laboratory stress task (Public Speaking). Saliva cortisol and self-reported mood levels were obtained at 6 time points prior to the stressor and during an extended recovery period. Furthermore, heart rate reactivity as an indicator of sympathetic activation was monitored continuously during the experimental procedure. We report a small, but significant effect of the BDNF Val66Met polymorphism on stress reactivity. More precisely, carriers of the met-allele showed a significantly attenuated HPA-axis and cardiovascular reactivity to the psychosocial stressor compared to subjects with the val/val genotype. Furthermore, the diminished physiological response in met-allele carriers was also attended by significantly lower self-reported ratings of perceived stress and nervousness. Our findings of a diminished endocrine and cardiovascular stress response in healthy male adults is consistent with a previously published study and adds further evidence for a crucial role of the BDNF Val66Met polymorphism in the modulation of stress reactivity. Copyright 2010. Published by Elsevier Ltd.

  1. Positive and negative social support and HPA-axis hyperactivity: Evidence from glucocorticoids in human hair.

    Science.gov (United States)

    Iob, Eleonora; Kirschbaum, Clemens; Steptoe, Andrew

    2018-06-12

    While positive social support is associated with lower prevalence of disease and better treatment outcomes, negative social relationships can instead have unfavourable consequences for several physical and mental health conditions. However, the specific mechanisms by which this nexus might operate remain poorly understood. Hypothalamic-pituitary-adrenal (HPA) axis hyperactivity owing to psychosocial stress has been proposed as a potential pathway underlying the link between social support and health. Hair glucocorticoids such as cortisol and cortisone are emerging as promising biomarkers of long-term retrospective HPA activation. Therefore, the aim of this investigation was to examine the effects of positive and negative experiences of social support within key relationships (i.e. spouse/partner, children, other family members, and friends) on cortisol and cortisone. These associations were tested in a sample of 2520 older adults (mean age 68.1) from the English Longitudinal Study of Ageing. Hair samples were collected in wave 6 (2012/13). To understand the impact of cumulative exposure to poor social support, the analysis used self-reported data from waves 4 (2008/09) and 6. Covariates included demographic, socioeconomic, lifestyle, and hair characteristics. In cross sectional analyses, lower positive support from all sources and specifically from children were associated with higher cortisol. Additionally, lower positive support from children was positively associated with cortisone. Similarly, higher overall negative support was related to higher cortisol, and greater negative support from children was also positively associated with cortisone. In longitudinal analyses, there was evidence for positive associations between hair glucocorticoids and cumulative exposure to poorer social support. Experiences of low positive and high negative social support, particularly from children, were both related to higher hair glucocorticoids. Hence, social relationships of

  2. Emotional exhaustion and overcommitment to work are differentially associated with hypothalamus-pituitary-adrenal (HPA) axis responses to a low-dose ACTH1-24 (Synacthen) and dexamethasone-CRH test in healthy school teachers.

    Science.gov (United States)

    Wolfram, Maren; Bellingrath, Silja; Feuerhahn, Nicolas; Kudielka, Brigitte M

    2013-01-01

    Evidence for a detrimental impact of chronic work stress on health has accumulated in epidemiological research. Recent studies indicate altered hypothalamus-pituitary-adrenal (HPA) axis regulation as a possible biological pathway underlying the link between stress and disease. However, the direction of dysregulation remains unclear, with reported HPA hyper- or hyporeactivity. To disentangle potential effects on different functional levels in the HPA axis, we examined responses using two pharmacological stimulation tests in 53 healthy teachers (31 females, 22 males; mean age: 49.3 years; age range: 30-64 years): a low-dose adrenocorticotrophic hormone (ACTH(1-24), Synacthen) test was used to assess adrenal cortex sensitivity and the combined dexamethasone-corticotropin releasing hormone (DEX-CRH) test to examine pituitary and adrenal cortex reactivity. Blood and saliva samples were collected at - 1,+15,+30,+45,+60,+90,+120 min. Emotional exhaustion (EE), the core dimension of burnout, was measured with the Maslach Burnout Inventory. Overcommitment (OC) was assessed according to Siegrist's effort-reward-imbalance model. We found a significant association between EE and higher plasma cortisol profiles after Synacthen (p = 0.045). By contrast, OC was significantly associated with attenuated ACTH (p = 0.045), plasma cortisol (p = 0.005), and salivary cortisol (p = 0.023) concentrations following DEX-CRH. Results support the notion of altered HPA axis regulation in chronically work-stressed teachers, with differential patterns of hyper- and hyporeactivity depending on individual stress condition and the tested functional level of the HPA axis.

  3. [Oxytocin: the hormone of love, trust and social bond. Clinical use in autism and social phobia].

    Science.gov (United States)

    Martin-Du Pan, R C

    2012-03-21

    Oxytocin, an octapeptide synthesized in the hypothalamus, stimulates milk election and uterine contractions. In the brain this hormone acts as a neuropeptide. It could inhibit through the GABAergic system the activity of limbic amygdala, which is involved in the response to fear. Oxytocin could also induce the protective behaviour of the mother towards its offspring through the dopaminergic system. In mankind, oxytocin plays a role in trust, empathy, generosity, stress and sexuality. Clinical studies are testing potential benefits of oxytocin administration in autism, depression and social phobia. Results are still preliminary.

  4. Resveratrol ameliorates chronic unpredictable mild stress-induced depression-like behavior: involvement of the HPA axis, inflammatory markers, BDNF, and Wnt/β-catenin pathway in rats

    Directory of Open Access Journals (Sweden)

    Yang X

    2017-10-01

    Full Text Available Xin-Hua Yang,1 Su-Qi Song,2 Yun Xu3 1Department of Pharmacy, Hefei Eighth People’s Hospital, Hefei, 2Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, 3Faculty of Pharmacy, Anhui Medical University, Hefei, China Abstract: Classic antidepressant drugs are modestly effective across the population and most are associated with intolerable side effects. Recently, numerous lines of evidence suggest that resveratrol (RES, a natural polyphenol, possesses beneficial therapeutic activity for depression. The aim of the present study was to explore whether RES exhibits an antidepressant-like effect in a depression model and to explore the possible mechanism. A depression model was established via chronic unpredictable mild stress (CUMS, after which the model rats in the RES and fluoxetine groups received a daily injection of RES or fluoxetine, respectively. The sucrose preference test, open field test, and forced swimming test were used to explore the antidepressant-like effects of RES. The activity of the hypothalamic–pituitary–adrenal (HPA axis was evaluated by detecting the plasma corticosterone concentration and hypothalamic mRNA expression of corticotrophin-releasing hormone. The plasma interleukin-6 (IL-6, C-reactive protein (CRP, and tumor necrosis factor-α (TNF-α concentrations were measured by enzyme-linked immunosorbent assay. Hippocampal protein expression of brain-derived neurotrophic factor (BDNF and the Wnt/β-catenin pathway were analyzed by western blot. The results showed that RES relieved depression-like behavior of CUMS rats, as indicated by the increased sucrose preference and the decreased immobile time. Rats that received RES treatment exhibited reduced plasma corticosterone levels and corticotrophin-releasing hormone mRNA expression in the hypothalamus, suggesting that the hyperactivity of the HPA axis in CUMS rats was reversed by RES. Moreover, after RES treatment, the rats exhibited increased

  5. Resveratrol ameliorates chronic unpredictable mild stress-induced depression-like behavior: involvement of the HPA axis, inflammatory markers, BDNF, and Wnt/β-catenin pathway in rats.

    Science.gov (United States)

    Yang, Xin-Hua; Song, Su-Qi; Xu, Yun

    2017-01-01

    Classic antidepressant drugs are modestly effective across the population and most are associated with intolerable side effects. Recently, numerous lines of evidence suggest that resveratrol (RES), a natural polyphenol, possesses beneficial therapeutic activity for depression. The aim of the present study was to explore whether RES exhibits an antidepressant-like effect in a depression model and to explore the possible mechanism. A depression model was established via chronic unpredictable mild stress (CUMS), after which the model rats in the RES and fluoxetine groups received a daily injection of RES or fluoxetine, respectively. The sucrose preference test, open field test, and forced swimming test were used to explore the antidepressant-like effects of RES. The activity of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by detecting the plasma corticosterone concentration and hypothalamic mRNA expression of corticotrophin-releasing hormone. The plasma interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) concentrations were measured by enzyme-linked immunosorbent assay. Hippocampal protein expression of brain-derived neurotrophic factor (BDNF) and the Wnt/β-catenin pathway were analyzed by western blot. The results showed that RES relieved depression-like behavior of CUMS rats, as indicated by the increased sucrose preference and the decreased immobile time. Rats that received RES treatment exhibited reduced plasma corticosterone levels and corticotrophin-releasing hormone mRNA expression in the hypothalamus, suggesting that the hyperactivity of the HPA axis in CUMS rats was reversed by RES. Moreover, after RES treatment, the rats exhibited increased plasma IL-6, CRP, and TNF-α concentrations. Furthermore, RES treatment upregulated the hippocampal protein levels of BDNF and the relative ratio of p-β-catenin/β-catenin while downregulating the relative ratio of p-GSK-3β/GSK-3β. Our findings suggest that RES improved

  6. Alterations in HPA-axis and autonomic nervous system functioning in childhood anxiety disorders point to a chronic stress hypothesis

    NARCIS (Netherlands)

    Dieleman, G.C.; Huizink, A.C.; Tulen, J.H.M.; Utens, E.M.W.J.; Creemers, H.E.; van der Ende, J.; Verhulst, F.C.

    2015-01-01

    Background: It is of debate whether or not childhood anxiety disorders (AD) can be captured by one taxonomic construct. This study examined whether perceived arousal (PA), autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis measures can distinguish children with different

  7. Alterations in HPA-axis and autonomic nervous system functioning in childhood anxiety disorders point to a chronic stress hypothesis

    NARCIS (Netherlands)

    Dieleman, Gwendolyn C.; Huizink, Anja C.; Tulen, Joke H. M.; Utens, Elisabeth M. W. J.; Creemers, Hanneke E.; van der Ende, Jan; Verhulst, Frank C.

    2015-01-01

    It is of debate whether or not childhood anxiety disorders (AD) can be captured by one taxonomic construct. This study examined whether perceived arousal (PA), autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis measures can distinguish children with different primary

  8. Excess portal venous long-chain fatty acids induce syndrome X via HPA axis and sympathetic activation

    NARCIS (Netherlands)

    Benthem, L; Keizer, Klaas-Jan; Wiegman, CH; De Boer, SF; Strubbe, JH; Steffens, AB; Kuipers, F; Scheurink, AJW

    2000-01-01

    We tested the hypothesis that excessive portal venous supply of long-chain fatty acids to the liver contributes to the development of insulin resistance via activation of the hypothalamus-pituitary-adrenal axis (HPA axis) and sympathetic system. Rats received an intraportal infusion of the

  9. The relation between hypothalamic-pituitary-adrenal (HPA) axis activity and age of onset of alcohol use

    NARCIS (Netherlands)

    Evans, B.E.; Greaves-Lord, K.; Euser, A.S.; Franken, I.H.A.; Huizink, A.C.

    2012-01-01

    Aims: Hypothalamic-pituitary-adrenal (HPA) axis activity may prove a viable biomarker for identifying those susceptible to alcohol use disorders. The purpose of this study was to examine the relation of the age at which adolescents begin drinking with diurnal and stress cortisol. Design:

  10. Change in parent-child conflict and the HPA-axis: Where should we be looking and for how long?

    Science.gov (United States)

    Kuhlman, Kate R.; Repetti, Rena L.; Reynolds, Bridget M.; Robles, Theodore F.

    2017-01-01

    Objective Salivary cortisol is increasingly used as a longitudinal indicator of change in neuroendocrine regulation and as a predictor of health outcomes in youth. The purpose of this study was to describe which indices of HPA-axis functioning are sensitive to changes in parent-child conflict over a three week period and to explore the time course under which these changes can be measured. Methods Youth (n = 47; ages 8–13) completed daily diaries of their conflict with parents for 56 days. On days 17–18 and 38–39, youth contributed saliva samples upon waking, 30-minutes post-waking, afternoon, and bedtime. We assessed change in average diurnal HPA-axis functioning between day 17–18 and day 38–39 as a function of the slopes of change in parent-child conflict over 3 weeks. Results Increasing parent-child conflict was positively associated with concurrent increases in total cortisol output (AUCg), flattening of the diurnal slope, and increases in cortisol at bedtime, but not with change in the cortisol awakening response (CAR). Further, associations between parent-child conflict and both AUCg and bedtime cortisol were observed with at least 14 days of daily diary reporting, whereas any additional ratings of conflict beyond 3 days of daily diaries did not improve model fit for changes in diurnal slope. Conclusions This study demonstrates the within-subject up-regulation of the HPA-axis across three weeks in a healthy sample of youth exposed to natural increases in family conflict. In particular, cortisol at bedtime may be the HPA-axis index that is most sensitive to change over time in parent-child conflict, above and beyond conflict occurring that day. Further, when testing associations between family stressors and diurnal cortisol, the optimal schedule for assessing parent-child conflict varies for different indices of HPA-axis functioning. PMID:26963373

  11. Association of HPA axis-related genetic variation with stress reactivity and aggressive behaviour in pigs

    Directory of Open Access Journals (Sweden)

    Muráni Eduard

    2010-08-01

    Full Text Available Abstract Background Stress, elicited for example by aggressive interactions, has negative effects on various biological functions including immune defence, reproduction, growth, and, in livestock, on product quality. Stress response and aggressiveness are mutually interrelated and show large interindividual variation, partly attributable to genetic factors. In the pig little is known about the molecular-genetic background of the variation in stress responsiveness and aggressiveness. To identify candidate genes we analyzed association of DNA markers in each of ten genes (CRH g.233C>T, CRHR1 c.*866_867insA, CRHBP c.51G>A, POMC c.293_298del, MC2R c.306T>G, NR3C1 c.*2122A>G, AVP c.207A>G, AVPR1B c.1084A>G, UCN g.1329T>C, CRHR2 c.*13T>C related to the hypothalamic-pituitary-adrenocortical (HPA axis, one of the main stress-response systems, with various stress- and aggression-related parameters at slaughter. These parameters were: physiological measures of the stress response (plasma concentrations of cortisol, creatine kinase, glucose, and lactate, adrenal weight (which is a parameter reflecting activity of the central branch of the HPA axis over time and aggressive behaviour (measured by means of lesion scoring in the context of psychosocial stress of mixing individuals with different aggressive temperament. Results The SNP NR3C1 c.*2122A>G showed association with cortisol concentration (p = 0.024, adrenal weight (p = 0.003 and aggressive behaviour (front lesion score, p = 0.012; total lesion score p = 0.045. The SNP AVPR1B c.1084A>G showed a highly significant association with aggressive behaviour (middle lesion score, p = 0.007; total lesion score p = 0.003. The SNP UCN g.1329T>C showed association with adrenal weight (p = 0.019 and aggressive behaviour (front lesion score, p = 0.029. The SNP CRH g.233C>T showed a significant association with glucose concentration (p = 0.002, and the polymorphisms POMC c.293_298del and MC2R c.306T>G with adrenal

  12. Can variation in hypothalamic-pituitary-adrenal (HPA-axis activity explain the relationship between depression and cognition in bipolar patients?

    Directory of Open Access Journals (Sweden)

    Marieke J van der Werf-Eldering

    Full Text Available Dysregulation of the hypothalamic-pituitary-adrenal (HPA axis is thought to be associated with more mood symptoms and worse cognitive functioning. This study examined whether variation in HPA axis activity underlies the association between mood symptoms and cognitive functioning.In 65 bipolar patients cognitive functioning was measured in domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory, executive functioning and an overall mean score. Severity of depression was assessed by the Inventory of Depressive Symptomatology-self rating version. Saliva cortisol measurements were performed to calculate HPA axis indicators: cortisol awakening response, diurnal slope, the evening cortisol level and the cortisol suppression on the dexamethasone suppression test. Regression analyses of depressive symptoms and cognitive functioning on each HPA axis indicator were performed. In addition we calculated percentages explanation of the association between depressive symptoms and cognition by HPA axis indicators. Depressive symptoms were associated with dysfunction in psychomotor speed, attentional switching and the mean score, as well as with attenuation in diurnal slope value. No association was found between HPA axis activity and cognitive functioning and HPA axis activity did not explain the associations between depressive symptoms and cognition.As our study is the first one in this field specific for bipolar patients and changes in HPA-axis activity did not seem to explain the association between severity of depressive symptoms and cognitive functioning in bipolar patients, future studies are needed to evaluate other factors that might explain this relationship.

  13. Interaction between 5-HTTLPR and BDNF Val66Met polymorphisms on HPA axis reactivity in preschoolers.

    Science.gov (United States)

    Dougherty, Lea R; Klein, Daniel N; Congdon, Eliza; Canli, Turhan; Hayden, Elizabeth P

    2010-02-01

    This study examined whether the interaction between the serotonin transporter promoter region (5-HTTLPR) and brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms was associated with hypothalamic-pituitary-adrenal (HPA) axis reactivity to stress. A community sample of 144 preschool-aged children was genotyped and exposed to stress-inducing laboratory tasks. Salivary cortisol was obtained at four time points during a standardized laboratory assessment before and after stressors involving separation from a parent and frustrating tasks. Children homozygous for the short-5-HTTLPR allele and carrying the Met-BDNF allele evidenced a significantly lower initial level of cortisol, followed by a positive increase in cortisol in response to the laboratory stressors. In contrast, children who were homozygous for the short-5-HTTLPR and the Val-BDNF alleles evidenced a greater decline in cortisol in response to the laboratory stressors. Findings indicated that the BDNF gene moderated the association between 5-HTTLPR and children's biological stress responses, suggesting that epistatic effects play a role in individual differences in stress regulation, and possibly genetic vulnerability to stress-related disorders. Copyright 2009 Elsevier B.V. All rights reserved.

  14. Hormones, stress, and cognition: The effects of glucocorticoids and oxytocin on memory

    Science.gov (United States)

    Wirth, Michelle M.

    2014-01-01

    Hormones have nuanced effects on learning and memory processes. The degree and direction of the effect (e.g., is memory impaired or enhanced?) depends on the dose, type and stage of memory, and type of material being learned, among other factors. This review will focus on two specific topics within the realm of effects of hormones on memory: (1) How glucocorticoids (the output hormones of the hypothalamic-pituitary-adrenal axis) affect long-term memory consolidation, retrieval, and working memory, with a focus on neural mechanisms and effects of emotion; and (2) How oxytocin affects memory, with emphasis on a speculative hypothesis that oxytocin might exert its myriad effects on human social cognition and behavior via impacts on more general cognitive processes. Oxytocin-glucocorticoid interactions will be briefly addressed. These effects of hormones on memory will also be considered from an evolutionary perspective. PMID:25893159

  15. The role of trauma in the hormonal interplay of cortisol, testosterone, and oxytocin in adolescent aggression.

    Science.gov (United States)

    Fragkaki, Iro; Cima, Maaike; Granic, Isabela

    2018-02-01

    Although numerous studies have examined the neuroendocrinology of aggression, the findings are mixed and focused on cortisol and testosterone. We argue that past findings remain inconclusive partly because the key roles of oxytocin and trauma have not been systematically integrated yet. Oxytocin is associated with social behavior and interacts with cortisol and testosterone, whereas trauma is a crucial risk factor of aggression that strongly affects hormonal activity. In this review, we investigate the role of trauma in the hormonal interplay of cortisol, testosterone, and oxytocin in aggression during adolescence. We first discuss how these hormones interact with each other and how trauma influences these interactions and then we propose a model that highlights the role of trauma in the hormonal interplay in aggression. We suggest that the timing of trauma has a distinct effect on hormonal activity and it should be integrated into any comprehensive model. Current trauma is linked to different levels of oxytocin, cortisol, testosterone, and testosterone/cortisol ratio than childhood trauma, but this distinction is also influenced by gender and type of aggression. We conclude that in order to better understand the neuroendocrinology of aggression, it is crucial to incorporate the investigation of oxytocin and trauma in future research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Differences in HPA axis reactivity to intimacy in women with and without histories of sexual trauma.

    Science.gov (United States)

    Martinson, Amber; Craner, Julia; Sigmon, Sandra

    2016-03-01

    Sexual trauma can lead to longstanding effects on individuals' intimacy functioning. The current study aimed to assess hypothalamic pituitary adrenal (HPA) axis functioning (i.e., cortisol reactivity) prior to (-5min), during (+15, +30, +45min), and following (+60min) an experimental manipulation of emotional closeness in a sample of women survivors of sexual trauma with varying levels of posttraumatic stress disorder (PTSD) symptomatology versus controls. Participants included 50 women, which were divided into 2 groups on the basis of a structured clinical interview: 26 women with a history of sexual trauma with and without PTSD (sexual trauma group), and 24 women without a history of sexual trauma or PTSD (controls). Participants came into the lab and participated in a 45min emotional closeness exercise with a male confederate and completed self-report questionnaires of closeness, state anxiety/depression, and cortisol assays at the aforementioned time points. Women with a history of sexual trauma exhibited a blunted cortisol response and greater anxious mood in reaction to the intimacy induction task compared to controls. Results also demonstrated that, unexpectedly, PTSD symptom severity scores among sexual trauma survivors were not associated with differential cortisol responding to the task compared to controls. Adaptive responses to stress are characterized by a relatively rapid cortisol increase followed by a steady decline. The results of this study demonstrated that women with a history of sexual trauma, in contrast, displayed a blunted cortisol response to an intimacy induction task. Both controls and women with a history of sexual trauma reported increased feelings of closeness to the male confederate in response to the intimacy induction task, suggesting that survivors were able to achieve similar adaptive feelings of intimacy when provided with the right conditions. Published by Elsevier Ltd.

  17. The stress-buffering effect of acute exercise: Evidence for HPA axis negative feedback.

    Science.gov (United States)

    Zschucke, Elisabeth; Renneberg, Babette; Dimeo, Fernando; Wüstenberg, Torsten; Ströhle, Andreas

    2015-01-01

    According to the cross-stressor adaptation hypothesis, physically trained individuals show lower physiological and psychological responses to stressors other than exercise, e.g. psychosocial stress. Reduced stress reactivity may constitute a mechanism of action for the beneficial effects of exercise in maintaining mental health. With regard to neural and psychoneuroendocrine stress responses, the acute stress-buffering effects of exercise have not been investigated yet. A sample of highly trained (HT) and sedentary (SED) young men was randomized to either exercise on a treadmill at moderate intensity (60-70% VO2max; AER) for 30 min, or to perform 30 min of "placebo" exercise (PLAC). 90 min later, an fMRI experiment was conducted using an adapted version of the Montreal Imaging Stress Task (MIST). The subjective and psychoneuroendocrine (cortisol and α-amylase) changes induced by the exercise intervention and the MIST were assessed, as well as neural activations during the MIST. Finally, associations between the different stress responses were analysed. Participants of the AER group showed a significantly reduced cortisol response to the MIST, which was inversely related to the previous exercise-induced α-amylase and cortisol fluctuations. With regard to the sustained BOLD signal, we found higher bilateral hippocampus (Hipp) activity and lower prefrontal cortex (PFC) activity in the AER group. Participants with a higher aerobic fitness showed lower cortisol responses to the MIST. As the Hipp and PFC are brain structures prominently involved in the regulation of the hypothalamus-pituitary-adrenal (HPA) axis, these findings indicate that the acute stress-buffering effect of exercise relies on negative feedback mechanisms. Positive affective changes after exercise appear as important moderators largely accounting for the effects related to physical fitness. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. HPA axis response to psychological stress and treatment retention in residential substance abuse treatment: a prospective study.

    Science.gov (United States)

    Daughters, Stacey B; Richards, Jessica M; Gorka, Stephanie M; Sinha, Rajita

    2009-12-01

    Substance abuse treatment programs are often characterized by high rates of premature treatment dropout, which increases the likelihood of relapse to drug use. Negative reinforcement models of addiction emphasize an individual's inability to tolerate stress as a key factor for understanding poor substance use treatment outcomes, and evidence indicates that dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis contributes to an individual's inability to respond adaptively to stress. The aim of the current study was to examine whether HPA axis response to stress is predictive of treatment retention among a sample of drug users in residential substance abuse treatment. Prospective study assessing treatment retention among 102 individuals enrolled in residential substance abuse treatment. Participants completed two computerized stress tasks, and HPA axis response to stress was measured via salivary cortisol at five time points from baseline (pre-stress) to 30 min post-stress exposure. The main outcome measures were treatment dropout (categorical) and total number of days in treatment (continuous). A significantly higher salivary cortisol response to stress was observed in treatment dropouts compared to treatment completers. Further, Cox proportional hazards survival analyses indicated that a higher peak cortisol response to stress was associated with a shorter number of days to treatment dropout. Results indicate that a higher salivary cortisol level in response to stress is associated with an inability to remain in substance abuse treatment. These findings are the first to document a biological marker of stress as a predictor of substance abuse treatment dropout, and support the development and implementation of treatments targeting this vulnerability.

  19. Repetitive stress leads to impaired cognitive function that is associated with DNA hypomethylation, reduced BDNF and a dysregulated HPA axis.

    Science.gov (United States)

    Makhathini, Khayelihle B; Abboussi, Oualid; Stein, Dan J; Mabandla, Musa V; Daniels, William M U

    2017-08-01

    Exposure to repetitive stress has a negative influence on cognitive-affective functioning, with growing evidence that these effects may be mediated by a dysregulated hypothalamic-pituitary-adrenal (HPA) axis, abnormal neurotrophic factor levels and its subsequent impact on hippocampal function. However, there are few data about the effect of repetitive stressors on epigenetic changes in the hippocampus. In the present study, we examine how repetitive restrain stress (RRS) affects cognitive-affective functioning, HPA axis regulation, brain-derived neurotrophic factor (BDNF) levels, and global hippocampal DNA methylation. RRS was induced in rats by restraining the animals for 6h per day for 28 days. The novel object recognition test (NORT) was used to assess cognitive functioning and the open field test (OFT) was performed to assess anxiety-like behavior during the last week of stress. Hippocampal BDNF levels, glucocorticoid (GR) and mineralocorticoid (MR) receptor mRNA were assessed using real-time PCR and confirmed with Western blot, while ELISAs were used to determine plasma corticosterone levels and the global methylation status of the hippocampus. Animals exposed to repetitive stress demonstrated significant alterations in the NORT and OFT, had significantly increased plasma corticosterone and significantly decreased hippocampal BDNF concentrations. The expression levels of GR and MR mRNA and protein levels of these genes were significantly decreased in the stressed group compared to control animals. The global DNA methylation of the hippocampal genome of stressed animals was also significantly decreased compared to controls. The data here are consistent with previous work emphasizing the role of the HPA axis and neurotrophic factors in mediating cognitive-affective changes after exposure to repetitive stressors. Our findings, however, extend the literature by indicating that epigenetic alterations in the hippocampal genome may also play an important role in the

  20. Forced swimming-induced oxytocin release into blood and brain: Effects of adrenalectomy and corticosterone treatment.

    Science.gov (United States)

    Torner, Luz; Plotsky, Paul M; Neumann, Inga D; de Jong, Trynke R

    2017-03-01

    The oxytocin (OXT) system is functionally linked to the HPA axis in a reciprocal and complex manner. Certain stressors are known to cause the simultaneous release of OXT and adrenocorticotrophic hormone (ACTH) followed by corticosterone (CORT). Furthermore, brain OXT attenuates ACTH and CORT responses. Although there are some indications of CORT influencing OXT neurotransmission, specific effects of CORT on neurohypophyseal or intra-hypothalamic release of OXT have not been studied in detail. In the present set of experiments, adult male rats were adrenalectomized (ADX) or sham-operated and fitted with a jugular vein catheter and/or microdialysis probe targeting the hypothalamic paraventricular nucleus (PVN). Blood samples and dialysates were collected before and after forced swimming (FS) and analyzed for CORT, ACTH and AVP concentrations (in plasma) and OXT concentrations (in plasma and dialysates). Experimental treatments included acute infusion of CORT (70 or 175μg/kg i.v.) 5min prior to FS, or subcutaneous placement of 40% CORT pellets resulting in stable CORT levels in the normal basal range. Although ADX did not alter basal OXT concentrations either in plasma or in microdialysates from the PVN, it did cause an exaggerated peripheral secretion of OXT and a blunted intra-PVN release of OXT in response to FS. CORT pellets did not influence either of these ADX-induced effects, while acute infusion of 175μg/kg CORT rescued the stress-induced rise in OXT release within the PVN and modestly increased peripheral OXT secretion. In conclusion, these results indicate that CORT regulates both peripheral and intracerebral OXT release, but in an independent manner. Whereas the peripheral secretion of OXT occurs simultaneously to HPA axis activation in response to FS and is modestly influenced by CORT, HPA axis activation and circulating CORT strongly contribute to the stress-induced stimulation of OXT release within the PVN. Copyright © 2016 Elsevier Ltd. All rights

  1. BDNF and glucocorticoids regulate corticotrophin-releasing hormone (CRH) homeostasis in the hypothalamus

    OpenAIRE

    Jeanneteau, Freddy D.; Lambert, W. Marcus; Ismaili, Naima; Bath, Kevin G.; Lee, Francis S.; Garabedian, Michael J.; Chao, Moses V.

    2012-01-01

    Regulation of the hypothalamic–pituitary–adrenal (HPA) axis is critical for adaptation to environmental changes. The principle regulator of the HPA axis is corticotrophin-releasing hormone (CRH), which is made in the parventricular nucleus and is an important target of negative feedback by glucocorticoids. However, the molecular mechanisms that regulate CRH are not fully understood. Disruption of normal HPA axis activity is a major risk factor of neuropsychiatric disorders in which decreased ...

  2. Antidepressant-like effects of salidroside on olfactory bulbectomy-induced pro-inflammatory cytokine production and hyperactivity of HPA axis in rats.

    Science.gov (United States)

    Yang, Shui-Jin; Yu, Hai-Yang; Kang, Dan-Yu; Ma, Zhan-Qiang; Qu, Rong; Fu, Qiang; Ma, Shi-Ping

    2014-09-01

    Salidroside (SA) is the primary bioactive marker compound in the standardized extracts from Rhodiola rosea. Although it has potential antidepressant activity in a rat behavioral despair model, the mechanisms of antidepressant effect for SA remain unclear. The objective of this study was to evaluate the antidepressant effects of SA and to discuss the potential mechanisms in olfactory bulbectomized (OBX) rats. SA of 20, 40 mg/kg (p.o.) for 2 weeks notably alleviated OBX-induced hyperactivity in open field test, decreased immobility time in TST and FST. Chronic treatment with SA could remarkably reduce TNF-α and IL-1β levels in hippocampus. Western blot showed that SA could markedly increase glucocorticoid receptor (GR) and brain-derived neurotrophic factor (BDNF) expression in the hippocampus. Besides, SA could also attenuate corticotropin-releasing hormone (CRH) expression in hypothalamus, as well as reducing significantly the levels of serum corticosterone. In conclusion, this study demonstrated that OBX rats treated with SA could significantly improve the depressive-like behaviors. The antidepressant mechanisms of SA might be associated with its anti-inflammatory effects and the regulation of HPA axis activity. Reversal of abnormalities of GR may be partly responsible for those effects. These findings suggested that SA might become a beneficial agent to prevent and treat the depression. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Maternal early-life trauma and affective parenting style: the mediating role of HPA-axis function.

    Science.gov (United States)

    Juul, Sarah H; Hendrix, Cassandra; Robinson, Brittany; Stowe, Zachary N; Newport, D Jeffrey; Brennan, Patricia A; Johnson, Katrina C

    2016-02-01

    A history of childhood trauma is associated with increased risk for psychopathology and interpersonal difficulties in adulthood and, for those who have children, impairments in parenting and increased risk of negative outcomes in offspring. Physiological and behavioral mechanisms are poorly understood. In the current study, maternal history of childhood trauma was hypothesized to predict differences in maternal affect and HPA axis functioning. Mother-infant dyads (N = 255) were assessed at 6 months postpartum. Mothers were videotaped during a 3-min naturalistic interaction, and their behavior was coded for positive, neutral, and negative affect. Maternal salivary cortisol was measured six times across the study visit, which also included an infant stressor paradigm. Results showed that childhood trauma history predicted increased neutral affect and decreased mean cortisol in the mothers and that cortisol mediated the association between trauma history and maternal affect. Maternal depression was not associated with affective measures or cortisol. Results suggest that early childhood trauma may disrupt the development of the HPA axis, which in turn impairs affective expression during mother-infant interactions in postpartum women. Interventions aimed at treating psychiatric illness in postpartum women may benefit from specific components to assess and treat trauma-related symptoms and prevent secondary effects on parenting.

  4. 17β-Estradiol is required for the sexually dimorphic effects of repeated binge-pattern alcohol exposure on the HPA axis during adolescence.

    Directory of Open Access Journals (Sweden)

    Magdalena M Przybycien-Szymanska

    Full Text Available Alcohol consumption during adolescence has long-term sexually dimorphic effects on anxiety behavior and mood disorders. We have previously shown that repeated binge-pattern alcohol exposure increased the expression of two critical central regulators of stress and anxiety, corticotrophin-releasing hormone (CRH and arginine vasopressin (AVP, in adolescent male rats. By contrast, there was no effect of alcohol on these same genes in adolescent females. Therefore, we tested the hypothesis that 17β-estradiol (E(2, the predominant sex steroid hormone in females, prevents alcohol-induced changes in CRH and AVP gene expression in the paraventricular nucleus (PVN of the hypothalamus. To test this hypothesis, postnatal day (PND 26 females were ovariectomized and given E(2 replacement or cholesterol as a control. Next, they were given an alcohol exposure paradigm of 1 saline alone, 2 acute (single dose or 3 a repeated binge-pattern. Our results showed that acute and repeated binge-pattern alcohol treatment increased plasma ACTH and CORT levels in both E(2- and Ch-treated groups, however habituation to repeated binge-pattern alcohol exposure was evident only in E(2-treated animals. Further, repeated binge-pattern alcohol exposure significantly decreased CRH and AVP mRNA in Ch-, but not E(2-treated animals, which was consistent with our previous observations in gonad intact females. We further tested the effects of E(2 and alcohol treatment on the activity of the wild type CRH promoter in a PVN-derived neuronal cell line. Alcohol increased CRH promoter activity in these cells and concomitant treatment with E(2 completely abolished the effect. Together our data suggest that E(2 regulates the reactivity of the HPA axis to a repeated stressor through modulation of the habituation response and further serves to maintain normal steady state mRNA levels of CRH and AVP in the PVN in response to a repeated alcohol stressor.

  5. Activation of ATP-sensitive potassium channel by iptakalim normalizes stress-induced HPA axis disorder and depressive behaviour by alleviating inflammation and oxidative stress in mouse hypothalamus.

    Science.gov (United States)

    Zhao, Xiao-Jie; Zhao, Zhan; Yang, Dan-Dan; Cao, Lu-Lu; Zhang, Ling; Ji, Juan; Gu, Jun; Huang, Ji-Ye; Sun, Xiu-Lan

    2017-04-01

    Stress-induced disturbance of the hypothalamic-pituitary-adrenal (HPA) axis is strongly implicated in incidence of mood disorders. A heightened neuroinflammatory response and oxidative stress play a fundamental role in the dysfunction of the HPA axis. We have previously demonstrated that iptakalim (Ipt), a new ATP-sensitive potassium (K-ATP) channel opener, could prevent oxidative injury and neuroinflammation against multiple stimuli-induced brain injury. The present study was to demonstrate the impacts of Ipt in stress-induced HPA axis disorder and depressive behavior. We employed 2 stress paradigms: 8 weeks of continuous restraint stress (chronic restraint stress, CRS) and 2h of restraint stress (acute restraint stress, ARS), to mimic both chronic stress and severe acute stress. Prolonged (4 weeks) and short-term (a single injection) Ipt treatment was administered 30min before each stress paradigm. We found that HPA axis was altered after stress, with different responses to CRS (lower ACTH and CORT, higher AVP, but normal CRH) and ARS (higher CRH, ACTH and CORT, but normal AVP). Both prolonged and short-term Ipt treatment normalized stress-induced HPA axis disorders and abnormal behaviors in mice. CRS and ARS up-regulated mRNA levels of inflammation-related molecules (TNFα, IL-1β, IL-6 and TLR4) and oxidative stress molecules (gp91phox, iNOS and Nrf2) in the mouse hypothalamus. Double immunofluorescence showed CRS and ARS increased microglia activation (CD11b and TNFα) and oxidative stress in neurons (NeuN and gp91phox), which were alleviated by Ipt. Therefore, the present study reveals that Ipt could prevent against stress-induced HPA axis disorders and depressive behavior by alleviating inflammation and oxidative stress in the hypothalamus. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Effects of early childhood trauma on hypothalamic-pituitary-adrenal (HPA) axis function in patients with Chronic Fatigue Syndrome.

    Science.gov (United States)

    Kempke, Stefan; Luyten, Patrick; De Coninck, Sarah; Van Houdenhove, Boudewijn; Mayes, Linda C; Claes, Stephan

    2015-02-01

    There is a paucity of studies that have investigated the assumption that early childhood trauma is associated with hypothalamic-pituitary-adrenal (HPA) axis dysfunction in Chronic Fatigue Syndrome (CFS). The current study is the first to simultaneously investigate relationships among early childhood trauma, cortisol activity, and cortisol stress reactivity to psychosocial stress in a sample of well-screened CFS patients. We also examined whether self-critical perfectionism (SCP) plays a mediating role in the potential relationship between early trauma and neurobiological stress responses. A total of 40 female patients diagnosed with CFS were asked to provide morning saliva cortisol samples (after awakening, 30min later, and 1h later) for seven consecutive days as a measure of cortisol activity. In addition, patients were exposed to the Trier Social Stress Test, a well-validated stress test, to investigate the relationship between early childhood trauma and cortisol stress reactivity. Before the start of the study, patients completed the Childhood Trauma Questionnaire-Short form (CTQ-SF) as a measure of early childhood trauma (i.e. sexual, physical and emotional traumatic experiences). SCP was measured with the Depressive Experiences Questionnaire (DEQ). Data were analyzed by calculating several indices of cortisol secretion (i.e. Cortisol Awakening Response and Area Under the Curve). There was no association between early childhood trauma and cortisol as measured over the 7-day period. However, emotional neglect was significantly negatively related to cortisol reactivity in the TSST. SCP did not significantly mediate this association. Findings of this study suggest that emotional neglect is associated with blunted HPA axis reactivity, congruent with the assumption that CFS may reflect loss of adaptability of the neuroendocrine stress response system in at least a subgroup of patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of CREB.

    Science.gov (United States)

    Xu, Ying; Ku, Baoshan; Tie, Lu; Yao, Haiyan; Jiang, Wengao; Ma, Xing; Li, Xuejun

    2006-11-29

    Curcuma longa is a major constituent of the traditional Chinese medicine Xiaoyao-san, which has been used to effectively manage stress and depression-related disorders in China. Curcumin is the active component of curcuma longa, and its antidepressant effects were described in our prior studies in mouse models of behavioral despair. We hypothesized that curcumin may also alleviate stress-induced depressive-like behaviors and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Thus in present study we assessed whether curcumin treatment (2.5, 5 and 10 mg/kg, p.o.) affects behavior in a chronic unpredictable stress model of depression in rats and examined what its molecular targets may be. We found that subjecting animals to the chronic stress protocol for 20days resulted in performance deficits in the shuttle-box task and several physiological effects, such as an abnormal adrenal gland weight to body weight (AG/B) ratio and increased thickness of the adrenal cortex as well as elevated serum corticosterone levels and reduced glucocorticoid receptor (GR) mRNA expression. These changes were reversed by chronic curcumin administration (5 or 10 mg/kg, p.o.). In addition, we also found that the chronic stress procedure induced a down-regulation of brain-derived neurotrophic factor (BDNF) protein levels and reduced the ratio of phosphorylated cAMP response element-binding protein (pCREB) to CREB levels (pCREB/CREB) in the hippocampus and frontal cortex of stressed rats. Furthermore, these stress-induced decreases in BDNF and pCREB/CREB were also blocked by chronic curcumin administration (5 or 10 mg/kg, p.o.). These results provide compelling evidence that the behavioral effects of curcumin in chronically stressed animals, and by extension humans, may be related to their modulating effects on the HPA axis and neurotrophin factor expressions.

  8. Stress in adolescence and drugs of abuse in rodent models: Role of dopamine, CRF, and HPA axis

    Science.gov (United States)

    Burke, Andrew R.; Miczek, Klaus A.

    2014-01-01

    Rationale Research on adolescence and drug abuse increased substantially in the past decade. However, drug-addiction related behaviors following stressful experiences during adolescence are less studied. We focus on rodent models of adolescent stress cross-sensitization to drugs of abuse. Objectives Review the ontogeny of behavior, dopamine, corticotropin-releasing factor (CRF), and the hypothalamic pituitary adrenal (HPA) axis in adolescent rodents. We evaluate evidence that stressful experiences during adolescence engender hypersensitivity to drugs of abuse and offer potential neural mechanisms. Results and Conclusions Much evidence suggests that final maturation of behavior, dopamine systems, and HPA axis occurs during adolescence. Stress during adolescence increases amphetamine- and ethanol-stimulated locomotion, preference, and self-administration under many conditions. The influence of adolescent stress on subsequent cocaine- and nicotine-stimulated locomotion and preference is less clear. The type of adolescent stress, temporal interval between stress and testing, species, sex, and the drug tested are key methodological determinants for successful cross-sensitization procedures. The sensitization of the mesolimbic dopamine system is proposed to underlie stress cross-sensitization to drugs of abuse in both adolescents and adults through modulation by CRF. Reduced levels of mesocortical dopamine appear to be a unique consequence of social stress during adolescence. Adolescent stress may reduce the final maturation of cortical dopamine through D2 dopamine receptor regulation of dopamine synthesis or glucocorticoid-facilitated pruning of cortical dopamine fibers. Certain rodent models of adolescent adversity are useful for determining neural mechanisms underlying the cross-sensitization to drugs of abuse. PMID:24370534

  9. Does stress affect the joints? Daily stressors, stress vulnerability, immune and HPA axis activity, and short-term disease and symptom fluctuations in rheumatoid arthritis

    NARCIS (Netherlands)

    Evers, A.W.M.; Verhoeven, E.W.M.; Middendorp, H. van; Sweep, F.C.; Kraaimaat, F.W.; Donders, A.R.T.; Eijsbouts, A.E.; Laarhoven, A.I.M. van; Brouwer, S.J.M. de; Wirken, L.; Radstake, T.R.D.J.; Riel, P.L.C.M. van

    2014-01-01

    OBJECTIVES: Both stressors and stress vulnerability factors together with immune and hypothalamus-pituitary-adrenal (HPA) axis activity components have been considered to contribute to disease fluctuations of chronic inflammatory diseases, such as rheumatoid arthritis (RA). The aim of the present

  10. HPA-axis activity and externalizing behavior problems in early adolescents from the general population : the role of comorbidity and gender The TRAILS study

    NARCIS (Netherlands)

    Marsman, Rianne; Swinkels, Sophie H. N.; Rosmalen, Judith G. M.; Oldehinkel, Albertine J.; Ormel, Johan; Buitelaar, Jan K.

    Contradictory findings on the relationship between hypothalamus-pituitary-adrenal (HPA)-axis activity and externalizing behavior problems could be due to studies not accounting for issues of comorbidity and gender. In a population-based cohort of 1768 (10- to 12-year-old) early adolescents, we used

  11. How does the brain deal with cumulative stress? A review with focus on developmental stress, HPA axis function and hippocampal structure in humans.

    Science.gov (United States)

    Frodl, Thomas; O'Keane, Veronica

    2013-04-01

    There is evidence that excessive stress exposure of the brain, mediated through the neurotoxic effects of cortisol and possibly neuroinflammation, causes damage to brain structure and function: the glucocorticoid cascade hypothesis. Functional changes of hypothalamic-pituitary-adrenal (HPA) axis as well as alterations in brain structures like the hippocampus have been consistently reported in major depression. However, there has not been a lot of emphasis on bringing findings from studies on early childhood stress, HPA axis functioning and hippocampal imaging together. This is the subject for this systematic review of the literature on how developmental stress, specifically childhood maltreatment, may impact on HPA axis function and hippocampal structure. We will also review the literature on the relationship between HPA axis function and hippocampal volume in healthy, depressed and other disease states. There is evidence that prenatal stress and childhood maltreatment is associated with an abnormally developing HPA system, as well as hippocampal volume reduction. Smaller hippocampal volumes are associated with increased cortisol secretion during the day. We conclude that a model integrating childhood maltreatment, cortisol abnormalities and hippocampal volume may need to take other factors into account, such as temperament, genetics or the presence of depression; to provide a cohesive explanation of all the findings. Finally, we have to conclude that the cascade hypothesis, mainly based on preclinical studies, has not been translated enough into humans. While there is evidence that early life maltreatment results in structural hippocampal changes and these are in turn more prominent in subjects with higher continuous cortisol secretion it is less clear which role early life maltreatment plays in HPA axis alteration. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Resveratrol ameliorates the anxiety- and depression-like behavior of subclinical hypothyroidism rat: possible involvement of the HPT axis, HPA axis, and Wnt/β-catenin pathway

    Directory of Open Access Journals (Sweden)

    Jinfang eGe

    2016-05-01

    Full Text Available Metabolic disease subclinical hypothyroidism (SCH is closely associated with depression-like behavior both in human and animal studies, and our previous studies have identified the antidepressant effect of resveratrol (RES in stressed rat model. The aim of this study was to investigate whether RES would manifest an antidepressant effect in SCH rat model and explore the possible mechanism. A SCH rat model was induced by hemi-thyroid electrocauterization, after which the model rats in the RES and LT4 groups received a daily intragastric injection of RES at the dose of 15 mg/kg or LT4 at the dose of 60 μg/kg for 16 days, respectively. The rats’ plasma concentrations of thyroid hormones were measured. Behavioral performance and hypothalamic-pituitary-adrenal (HPA activity were evaluated. The protein expression levels of the Wnt/β-catenin in the hippocampus were detected by western blot. The results showed that RES treatment down-regulated the elevated plasma thyroid stimulating hormone (TSH concentration and the hypothalamic mRNA expression of thyrotropin releasing hormone (TRH in the SCH rats. RES-treated rats showed increased rearing frequency and distance in the OFT, increased sucrose preference in the SPT, and decreased immobility in the FST compared with SCH rats. The ratio of the adrenal gland weight to body weight, the plasma corticosterone levels and the hypothalamic CRH mRNA expression were reduced in the RES-treated rats. Moreover, RES treatment up-regulated the relative ratio of phosphorylated-GSK3β (p-GSK3β/GSK3β and protein levels of p-GSK3β, cyclinD1 and c-myc, while down-regulating the relative ratio of phosphorylated-β-catenin (p-β-catenin/β-catenin and expression of GSK3β in the hippocampus. These findings suggest that RES exerts anxiolytic- and antidepressant-like effect in SCH rats by down-regulating hyperactivity of the HPA axis and regulating both the HPT axis and the Wnt/β-catenin pathway.

  13. Sex differences in the outcome of juvenile social isolation on HPA axis function in rats.

    Science.gov (United States)

    Pisu, M G; Garau, A; Boero, G; Biggio, F; Pibiri, V; Dore, R; Locci, V; Paci, E; Porcu, P; Serra, M

    2016-04-21

    Women are more likely than men to suffer from anxiety disorders and major depression. These disorders share hyperresponsiveness to stress as an etiological factor. Thus, sex differences in brain arousal systems and their regulation by chronic stress may account for the increased vulnerability to these disorders in women. Social isolation is a model of early life stress that results in neurobiological alterations leading to increased anxiety-like and depressive-like behaviors. Here we investigated the sex difference in the effects of post-weaning social isolation on acute stress sensitivity and behavior in rats. In both sexes, social isolation at weaning reduced basal levels of the neuroactive steroid allopregnanolone in the brain and of corticosterone in plasma. Moreover, acute stress increased plasma corticosterone levels in both group-housed and socially isolated male and female rats; however this effect was greater in male than female rats subjected to social isolation. Intriguingly, group-housed female rats showed no change in plasma and brain levels of allopregnanolone after acute foot-shock stress. The absence of stress-induced effects on allopregnanolone synthesis might be due to the physiologically higher levels of this hormone in females vs. males. Accordingly, increasing allopregnanolone levels in male rats blunted the response to foot-shock stress in these animals. Socially isolated male, but not female, rats also display depressive-like behavior and increased hippocampal brain-derived neurotrophic factor (BDNF). The ovarian steroids could "buffer" the effect of this adverse experience in females on these parameters. Finally, the dexamethasone (DEX) suppression test indicated that the chronic stress associated with social isolation impairs feedback inhibition in both sexes in which an increase in the abundance of glucocorticoid receptors (GRs) in the hippocampus was found. Altogether, these results demonstrate that social isolation affects neuroendocrine

  14. Ovarian hormone deprivation reduces oxytocin expression in Paraventricular Nucleus preautonomic neurons and correlates with baroreflex impairment in rats

    Directory of Open Access Journals (Sweden)

    Vitor Ulisses De Melo

    2016-10-01

    Full Text Available The prevalence of cardiovascular diseases including hypertension increases dramatically in women after menopause, however the mechanisms involved remain incompletely understood. Oxytocinergic (OTergic neurons are largely present within the paraventricular nucleus of the hypothalamus (PVN. Several studies have shown that OTergic drive from PVN to brainstem increases baroreflex sensitivity and improves autonomic control of the circulation. Since preautonomic PVN neurons express different types of estrogen receptors, we hypothesize that ovarian hormone deprivation causes baroreflex impairment, autonomic imbalance and hypertension by negatively impacting OTergic drive and oxytocin levels in pre-autonomic neurons. Here, we assessed oxytocin gene and protein expression (qPCR and immunohistochemistry within PVN subnuclei in sham-operated and ovariectomized Wistar rats. Conscious hemodynamic recordings were used to assess resting blood pressure and heart rate and the autonomic modulation of heart and vessels was estimated by power spectral analysis. We observed that the ovarian hormone deprivation in ovariectomized rats decreased baroreflex sensitivity, increased sympathetic and reduced vagal outflows to the heart and augmented the resting blood pressure. Of note, ovariectomized rats had reduced PVN oxytocin mRNA and protein expression in all pre-autonomic PVN subnuclei. Furthermore, reduced PVN oxytocin protein levels were positively correlated with decreased baroreflex sensitivity and negatively correlated with increased LF/HF ratio. These findings suggest that reduced oxytocin expression in OTergic neurons of the PVN contributes to the baroreflex dysfunction and autonomic dysregulation observed with ovarian hormone deprivation.

  15. Basal functioning of the hypothalamic-pituitary-adrenal (HPA) axis and psychological distress in recreational ecstasy polydrug users.

    Science.gov (United States)

    Wetherell, Mark A; Montgomery, Catharine

    2014-04-01

    Ecstasy (MDMA) is a psychostimulant drug which is increasingly associated with psychobiological dysfunction. While some recent studies suggest acute changes in neuroendocrine function, less is known about long-term changes in HPA functionality in recreational users. The current study is the first to explore the effects of ecstasy-polydrug use on psychological distress and basal functioning of the HPA axis through assessing the secretion of cortisol across the diurnal period. Seventy-six participants (21 nonusers, 29 light ecstasy-polydrug users, 26 heavy ecstasy-polydrug users) completed a substance use inventory and measures of psychological distress at baseline, then two consecutive days of cortisol sampling (on awakening, 30 min post awakening, between 1400 and 1600 hours and pre bedtime). On day 2, participants also attended the laboratory to complete a 20-min multitasking stressor. Both user groups exhibited significantly greater levels of anxiety and depression than nonusers. On day 1, all participants exhibited a typical cortisol profile, though light users had significantly elevated levels pre-bed. On day 2, heavy users demonstrated elevated levels upon awakening and all ecstasy-polydrug users demonstrated elevated pre-bed levels compared to non-users. Significant between group differences were also observed in afternoon cortisol levels and in overall cortisol secretion across the day. The increases in anxiety and depression are in line with previous observations in recreational ecstasy-polydrug users. Dysregulated diurnal cortisol may be indicative of inappropriate anticipation of forthcoming demands and hypersecretion may lead to the increased psychological and physical morbidity associated with heavy recreational use of ecstasy.

  16. BDNF Val66Met polymorphism is associated with HPA axis reactivity to psychological stress characterized by genotype and gender interactions.

    Science.gov (United States)

    Shalev, Idan; Lerer, Elad; Israel, Salomon; Uzefovsky, Florina; Gritsenko, Inga; Mankuta, David; Ebstein, Richard P; Kaitz, Marsha

    2009-04-01

    A key protein in maintaining neuronal integrity throughout the life span is brain-derived neurotrophic factor (BDNF). The BDNF gene is characterized by a functional polymorphism, which has been associated with stress-related disorders such as anxiety-related syndromes and depression, prompting us to examine individual responses by Genotype and Sex to a standardized social stress paradigm. Gender differences in BDNFxstress responses were posited because estrogen induces synthesis of BDNF in several brain regions. 97 university students (51 females and 46 males) participated in a social stress procedure (Trier Social Stress Test, TSST). Indices of stress were derived from repeated measurement of cortisol, blood pressure, and heart rate during the TSST. All subjects were genotyped for the Val66Met polymorphism. Tests of within-subject effects showed a significant three-way interaction (SPSS GLM repeated measures: Time (eight levels)xBDNF (val/val, val/met)xSex: p=0.0002), which reflects gender differences in the pattern of cortisol rise and decline during the social challenge. In male subjects, val/val homozygotes showed a greater rise in salivary cortisol than val/met heterozygotes. In female subjects, there was a trend for the opposite response, which is significant when area under the curve increase (AUCi) was calculated for the val/val homozygotes to show the lowest rise. Overall, the same pattern of results was observed for blood pressure and heart rate. These results indicate that a common, functionally significant polymorphism in the BDNF gene modulates HPA axis reactivity and regulation during the TSST differently in men and women. Findings may be related to gender differences in reactivity and vulnerability to social stress.

  17. Brain catalase activity inhibition as well as opioid receptor antagonism increases ethanol-induced HPA axis activation.

    Science.gov (United States)

    Pastor, Raúl; Sanchis-Segura, Carles; Aragon, Carlos M G

    2004-12-01

    Growing evidence indicates that brain catalase activity is involved in the psychopharmacological actions of ethanol. Recent data suggest that participation of this enzymatic system in some ethanol effects could be mediated by the endogenous opioid system. The present study assessed whether brain catalase has a role in ethanol-induced activation of the HPA axis, a neuroendocrine system modulated by the endogenous opioid neurotransmission. Swiss male mice received an intraperitoneal injection of the catalase inhibitor 3-amino-1,2,4-triazole (AT; 0-1 g/kg), and 0 to 20 hr after this administration, animals received an ethanol (0-4 g/kg; intraperitoneally) challenge. Thirty, 60, or 120 min after ethanol administration, plasma corticosterone levels were determined immunoenzymatically. In addition, we tested the effects of 45 mg/kg of cyanamide (another catalase inhibitor) and 0 to 2 mg/kg of naltrexone (nonselective opioid receptor antagonist) on ethanol-induced enhancement in plasma corticosterone values. The present study revealed that AT boosts ethanol-induced increase in plasma corticosterone levels in a dose- and time-dependent manner. However, it did not affect corticosterone values when measured after administration of saline, cocaine (4 mg/kg, intraperitoneally), or morphine (30 mg/kg, intraperitoneally). The catalase inhibitor cyanamide (45 mg/kg, intraperitoneally) also increased ethanol-related plasma corticosterone levels. These effects of AT and cyanamide on ethanol-induced corticosterone values were observed under treatment conditions that decreased significantly brain catalase activity. Indeed, a significant correlation between effects of catalase manipulations on both variables was found. Finally, we found that the administration of naltrexone enhanced the levels of plasma corticosterone after the administration of saline or ethanol. This study shows that the inhibition of brain catalase increases ethanol-induced plasma corticosterone levels. Results are

  18. Colocalization of corticotropin-releasing hormone and oestrogen receptor-alpha in the paraventricular nucleus of the hypothalamus in mood disorders

    NARCIS (Netherlands)

    Bao, Ai-Min; Hestiantoro, Andon; van Someren, Eus J. W.; Swaab, Dick F.; Zhou, Jiang-Ning

    2005-01-01

    Oestrogens may modulate the activity of the hypothalamic-pituitary-adrenal (HPA) axis. The present study was to investigate whether the activity of the HPA axis in mood disorders might be directly modulated by oestrogens via oestrogen receptors (ORs) in the corticotropin-releasing hormone (CRH)

  19. In Obesity, HPA Axis Activity Does Not Increase with BMI, but Declines with Aging: A Meta-Analysis of Clinical Studies.

    Directory of Open Access Journals (Sweden)

    Judit Tenk

    Full Text Available Obesity is one of the major public health challenges worldwide. It involves numerous endocrine disorders as etiological factors or as complications. Previous studies strongly suggested the involvement of the hypothalamic-pituitary-adrenal (HPA axis activity in obesity, however, to date, no consistent trend in obesity-associated alterations of the HPA axis has been identified. Aging has been demonstrated to aggravate obesity and to induce abnormalities of the HPA axis. Thus, the question arises whether obesity is correlated with peripheral indicators of HPA function in adult populations.We aimed to meta-analyze literature data on peripheral cortisol levels as indicators of HPA activity in obesity during aging, in order to identify possible explanations for previous contradictory findings and to suggest new approaches for future clinical studies.3,596 records were identified through searching of PubMed, Embase and Cochrane Library Database. Altogether 26 articles were suitable for analyses.Empirical research papers were eligible provided that they reported data of healthy adult individuals, included body mass index (BMI and measured at least one relevant peripheral cortisol parameter (i.e., either morning blood cortisol or 24-h urinary free cortisol.We used random effect models in each of the meta-analyses calculating with the DerSimonian and Laird weighting methods. I-squared indicator and Q test were performed to assess heterogeneity. Meta-regression was applied to explore the effect of BMI and age on morning blood and urinary free cortisol levels. To assess publication bias Egger's test was used.Obesity did not show any correlation with the studied peripheral cortisol values. On the other hand, peripheral cortisol levels declined with aging within the obese, but not in the non-obese groups.Our analysis demonstrated that obesity or healthy aging does not lead to enhanced HPA axis activity, peripheral cortisol levels rather decline with aging.

  20. In Obesity, HPA Axis Activity Does Not Increase with BMI, but Declines with Aging: A Meta-Analysis of Clinical Studies.

    Science.gov (United States)

    Tenk, Judit; Mátrai, Péter; Hegyi, Péter; Rostás, Ildikó; Garami, András; Szabó, Imre; Solymár, Margit; Pétervári, Erika; Czimmer, József; Márta, Katalin; Mikó, Alexandra; Füredi, Nóra; Párniczky, Andrea; Zsiborás, Csaba; Balaskó, Márta

    2016-01-01

    Obesity is one of the major public health challenges worldwide. It involves numerous endocrine disorders as etiological factors or as complications. Previous studies strongly suggested the involvement of the hypothalamic-pituitary-adrenal (HPA) axis activity in obesity, however, to date, no consistent trend in obesity-associated alterations of the HPA axis has been identified. Aging has been demonstrated to aggravate obesity and to induce abnormalities of the HPA axis. Thus, the question arises whether obesity is correlated with peripheral indicators of HPA function in adult populations. We aimed to meta-analyze literature data on peripheral cortisol levels as indicators of HPA activity in obesity during aging, in order to identify possible explanations for previous contradictory findings and to suggest new approaches for future clinical studies. 3,596 records were identified through searching of PubMed, Embase and Cochrane Library Database. Altogether 26 articles were suitable for analyses. Empirical research papers were eligible provided that they reported data of healthy adult individuals, included body mass index (BMI) and measured at least one relevant peripheral cortisol parameter (i.e., either morning blood cortisol or 24-h urinary free cortisol). We used random effect models in each of the meta-analyses calculating with the DerSimonian and Laird weighting methods. I-squared indicator and Q test were performed to assess heterogeneity. Meta-regression was applied to explore the effect of BMI and age on morning blood and urinary free cortisol levels. To assess publication bias Egger's test was used. Obesity did not show any correlation with the studied peripheral cortisol values. On the other hand, peripheral cortisol levels declined with aging within the obese, but not in the non-obese groups. Our analysis demonstrated that obesity or healthy aging does not lead to enhanced HPA axis activity, peripheral cortisol levels rather decline with aging.

  1. Does stress affect the joints? Daily stressors, stress vulnerability, immune and HPA axis activity, and short-term disease and symptom fluctuations in rheumatoid arthritis.

    Science.gov (United States)

    Evers, Andrea W M; Verhoeven, Elisabeth W M; van Middendorp, Henriët; Sweep, Fred C G J; Kraaimaat, Floris W; Donders, A Rogier T; Eijsbouts, Agnes E; van Laarhoven, Antoinette I M; de Brouwer, Sabine J M; Wirken, Lieke; Radstake, Timothy R D J; van Riel, Piet L C M

    2014-09-01

    Both stressors and stress vulnerability factors together with immune and hypothalamus-pituitary-adrenal (HPA) axis activity components have been considered to contribute to disease fluctuations of chronic inflammatory diseases, such as rheumatoid arthritis (RA). The aim of the present study was to investigate whether daily stressors and worrying as stress vulnerability factor as well as immune and HPA axis activity markers predict short-term disease activity and symptom fluctuations in patients with RA. In a prospective design, daily stressors, worrying, HPA axis (cortisol) and immune system (interleukin (IL)-1β, IL-6, IL-8, interferon (IFN)-γ, tumour necrosis factor α) markers, clinical and self-reported disease activity (disease activity score in 28 joints, RA disease activity index), and physical symptoms of pain and fatigue were monitored monthly during 6 months in 80 RA patients. Multilevel modelling indicated that daily stressors predicted increased fatigue in the next month and that worrying predicted increased self-reported disease activity, swollen joint count and pain in the next month. In addition, specific cytokines of IL-1β and IFN-γ predicted increased fatigue 1 month later. Overall, relationships remained relatively unchanged after controlling for medication use, disease duration and demographic variables. No evidence was found for immune and HPA axis activity markers as mediators of the stress-disease relationship. Daily stressors and the stress-vulnerability factor worrying predict indicators of the short-term course of RA disease activity and fatigue and pain, while specific cytokines predict short-term fluctuations of fatigue. These stress-related variables and immune markers seem to affect different aspects of disease activity or symptom fluctuations independently in RA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  2. Recovery by N-acetylcysteine from subchronic exposure to Imidacloprid-induced hypothalamic-pituitary-adrenal (HPA) axis tissues injury in male rats.

    Science.gov (United States)

    Annabi, Alya; Dhouib, Ines Bini; Lamine, Aicha Jrad; El Golli, Nargès; Gharbi, Najoua; El Fazâa, Saloua; Lasram, Mohamed Montassar

    2015-01-01

    Imidacloprid is the most important example of the neonicotinoid insecticides known to target the nicotinic acetylcholine receptor in insects, and potentially in mammals. N-Acetyl-l-cysteine (NAC) has been shown to possess curative effects in experimental and clinical investigations. The present study was designed to evaluate the recovery effect of NAC against Imidacloprid-induced oxidative stress and cholinergic transmission alteration in hypothalamic-pituitary-adrenal (HPA) axis of male rats following subchronic exposure. About 40 mg/kg of Imidacloprid was administered daily by intragastric intubation and 28 days later, the rats were sacrificed and HPA axis tissues were removed for different analyses. Imidacloprid increased adrenal relative weight and cholesterol level indicating an adaptive stage of the general alarm reaction to stress. Moreover, Imidacloprid caused a significant increase in malondialdehyde level, the antioxidants catalase, superoxide dismutase and glutathione-S-transferase showed various alterations following administration and significant depleted thiols content was only recorded in hypothalamic tissue. Furthermore, the hypothalamic and pituitary acetylcholinesterase activity and calcium level were significantly increased highlighting the alteration of cholinergic activity. The present findings revealed that HPA axis is a sensitive target to Imidacloprid (IMI). Interestingly, the use of NAC for only 7 days post-exposure to IMI showed a partial therapeutic effect against Imidacloprid toxicity.

  3. Effects of selective serotonin reuptake inhibitor treatment on plasma oxytocin and cortisol in major depressive disorder.

    Science.gov (United States)

    Keating, Charlotte; Dawood, Tye; Barton, David A; Lambert, Gavin W; Tilbrook, Alan J

    2013-04-29

    Oxytocin is known for its capacity to facilitate social bonding, reduce anxiety and for its actions on the stress hypothalamopituitary adrenal (HPA) axis. Since oxytocin can physiologically suppress activity of the HPA axis, clinical applications of this neuropeptide have been proposed in conditions where the function of the HPA axis is dysregulated. One such condition is major depressive disorder (MDD). Dysregulation of the HPA system is the most prominent endocrine change seen with MDD, and normalizing the HPA axis is one of the major targets of recent treatments. The potential clinical application of oxytocin in MDD requires improved understanding of its relationship to the symptoms and underlying pathophysiology of MDD. Previous research has investigated potential correlations between oxytocin and symptoms of MDD, including a link between oxytocin and treatment related symptom reduction. The outcomes of studies investigating whether antidepressive treatment (pharmacological and non-pharmacological) influences oxytocin concentrations in MDD, have produced conflicting outcomes. These outcomes suggest the need for an investigation of the influence of a single treatment class on oxytocin concentrations, to determine whether there is a relationship between oxytocin, the HPA axis (e.g., oxytocin and cortisol) and MDD. Our objective was to measure oxytocin and cortisol in patients with MDD before and following treatment with selective serotonin reuptake inhibitors, SSRI. We sampled blood from arterial plasma. Patients with MDD were studied at the same time twice; pre- and post- 12 weeks treatment, in an unblinded sequential design (clinicaltrials.govNCT00168493). Results did not reveal differences in oxytocin or cortisol concentrations before relative to following SSRI treatment, and there were no significant relationships between oxytocin and cortisol, or these two physiological variables and psychological symptom scores, before or after treatment. These outcomes

  4. Ozone-Induced Pulmonary Injury and Inflammation are Modulated by Adrenal-Derived Stress Hormones

    Science.gov (United States)

    Ozone exposure promotes pulmonary injury and inflammation. Previously we have characterized systemic changes that occur immediately after acute ozone exposure and are mediated by neuro-hormonal stress response pathway. Both HPA axis and sympathetic tone alterations induce the rel...

  5. Escitalopram alters gene expression and HPA axis reactivity in rats following chronic overexpression of corticotropin-releasing factor from the central amygdala

    Science.gov (United States)

    Flandreau, Elizabeth I.; Bourke, Chase H.; Ressler, Kerry J.; Vale, Wylie W.; Nemeroff, Charles B.; Owens, Michael J.

    2013-01-01

    Summary We have previously demonstrated that viral-mediated overexpression of corticotropin-releasing factor (CRF) within the central nucleus of the amygdala (CeA) reproduces many of the behavioral and endocrine consequences of chronic stress. The present experiment sought to determine whether administration of the selective serotonin reuptake inhibitor (SSRI) escitalopram reverses the adverse effects of CeA CRF overexpression. In a 2 × 2 design, adult male rats received bilateral infusions of a control lentivirus or a lentivirus in which a portion of the CRF promoter is used to drive increased expression of CRF peptide. Four weeks later, rats were then implanted with an Alzet minipump to deliver vehicle or 10 mg/kg/day escitalopram for a 4-week period of time. The defensive withdrawal (DW) test of anxiety and the sucrose-preference test (SPT) of anhedonia were performed both before and after pump implantation. Additional post-implant behavioral tests included the elevated plus maze (EPM) and social interaction (SI) test. Following completion of behavioral testing, the dexamethasone/CRF test was performed to assess HPA axis reactivity. Brains were collected and expression of HPA axis-relevant transcripts were measured using in situ hybridization. Amygdalar CRF overexpression increased anxiety-like behavior in the DW test at week eight, which was only partially prevented by escitalopram. In both CRF-overexpressing and control groups, escitalopram decreased hippocampal CRF expression while increasing hypothalamic and hippocampal expression of the glucocorticoid receptor (GR). These gene expression changes were associated with a significant decrease in HPA axis reactivity in rats treated with escitalopram. Interestingly, escitalopram increased the rate of weight gain only in rats overexpressing CRF. Overall these data support our hypothesis that amygdalar CRF is critical in anxiety-like behavior; because the antidepressant was unable to reverse behavioral

  6. Saikosaponin D relieves unpredictable chronic mild stress induced depressive-like behavior in rats: involvement of HPA axis and hippocampal neurogenesis.

    Science.gov (United States)

    Li, Hong-Yan; Zhao, Ying-Hua; Zeng, Min-Jie; Fang, Fang; Li, Min; Qin, Ting-Ting; Ye, Lu-Yu; Li, Hong-Wei; Qu, Rong; Ma, Shi-Ping

    2017-11-01

    Saikosaponin D (SSD), a major bioactive component isolated from Radix Bupleuri, has been reported to exert neuroprotective properties. The present study was designed to investigate the anti-depressant-like effects and the potential mechanisms of SSD. Behavioural tests including sucrose preference test (SPT), open field test (OFT) and forced swim test (FST) were performed to study the antidepressant-like effects of SSD. In addition, we examined corticosterone and glucocorticoid receptor (GR) levels to evaluate hypothalamic-pituitary-adrenal (HPA) axis function. Furthermore, hippocampal neurogenesis was assessed by testing doublecortin (DCX) levels, and neurotrophic molecule levels were also investigated in the hippocampus of rats. We found that unpredictable chronic mild stress (UCMS) rats displayed lost body weight, decreased sucrose consumption in SPT, reduced locomotive activity in OFT, and increased immobility time in FST. Chronic treatment with SSD (0.75, 1.50 mg/kg) remarkably ameliorated the behavioral deficiency induced by UCMS procedure. SSD administration downregulated elevated serum corticosterone levels, as well as alleviated the suppression of GR expression and nuclear translocation caused by UCMS, suggesting that SSD is able to remit the dysfunction of HPA axis. In addition, Western blot and immunohistochemistry analysis showed that SSD treatment significantly increased the generation of neurons in the hippocampus of UCMS rats indicated by elevated DCX levels. Moreover, hippocampal neurotrophic molecule levels of UCMS rats such as phosphorylated cAMP response element binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) were raised after SSD treatment. Together, Our results suggest that SSD opposed UCMS-induced depressive behaviors in rats, which was mediated, partially, by the enhancement of HPA axis function and consolidation of hippocampal neurogenesis.

  7. Interplay of oxytocin, vasopressin, and sex hormones in the regulation of social recognition.

    Science.gov (United States)

    Gabor, Christopher S; Phan, Anna; Clipperton-Allen, Amy E; Kavaliers, Martin; Choleris, Elena

    2012-02-01

    Social Recognition is a fundamental skill that forms the basis of behaviors essential to the proper functioning of pair or group living in most social species. We review here various neurobiological and genetic studies that point to an interplay of oxytocin (OT), arginine-vasopressin (AVP), and the gonadal hormones, estrogens and testosterone, in the mediation of social recognition. Results of a number of studies have shown that OT and its actions at the medial amygdala seem to be essential for social recognition in both sexes. Estrogens facilitate social recognition, possibly by regulating OT production in the hypothalamus and the OT receptors at the medial amygdala. Estrogens also affect social recognition on a rapid time scale, likely through nongenomic actions. The mechanisms of these rapid effects are currently unknown but available evidence points at the hippocampus as the possible site of action. Male rodents seem to be more dependent on AVP acting at the level of the lateral septum for social recognition than female rodents. Results of various studies suggest that testosterone and its metabolites (including estradiol) influence social recognition in males primarily through the AVP V1a receptor. Overall, it appears that gonadal hormone modulation of OT and AVP regulates and fine tunes social recognition and those behaviors that depend upon it (e.g., social bonds, social hierarchies) in a sex specific manner. This points at an important role for these neuroendocrine systems in the regulation of the sex differences that are evident in social behavior and of sociality as a whole.

  8. Two-year stability of individual differences in (para)sympathetic and HPA-axis responses to public speaking in childhood and adolescence.

    Science.gov (United States)

    van den Bos, Esther; Westenberg, P Michiel

    2015-03-01

    Long-term stability of individual differences in stress responses has repeatedly been demonstrated in adults, but few studies have investigated the development of stability in adolescence. The present study was the first to investigate the stability of individual differences in heart rate, parasympathetic (RMSSD, pNN50, HF), sympathetic (LF/HF, SC), and HPA-axis (salivary cortisol) responses in a youth sample (8-19 years). Responses to public speaking were measured twice over 2 years. Stability was moderate for absolute responses and task delta responses of HR, RMSSD, pNN50, and HF. Stability was lower for SC and task delta responses of LF/HF and cortisol. Anticipation delta responses showed low stability for HR and cortisol. The latter was moderated by age or puberty, so that individual differences were more stable in more mature individuals. The results support the suggestion that stress responses may be reset during adolescence, but only for the HPA axis. © 2014 Society for Psychophysiological Research.

  9. HPA axis response to social stress is attenuated in schizophrenia but normal in depression: evidence from a meta-analysis of existing studies.

    Science.gov (United States)

    Ciufolini, Simone; Dazzan, Paola; Kempton, Matthew J; Pariante, Carmine; Mondelli, Valeria

    2014-11-01

    We conducted a meta-analysis to investigate the HPA axis response to social stress in studies that used the Trier Social Stress Test (TSST), or comparable distressing paradigms, in individuals with either depression or schizophrenia. Sample size-adjusted effect sizes (Hedge's g statistic) were calculated to estimate the HPA axis stress response to social stress. We used a meta-regression model to take into account the moderating effect of the baseline cortisol level. Participants with depression show an activation pattern to social stress similar to that of healthy controls. Despite a normal cortisol production rate, individuals with schizophrenia have lower cortisol levels than controls both in anticipation and after exposure to social stress. Participants with depression and higher cortisol levels before the task have an increased cortisol production and reached higher cortisol levels during the task. This may be explained by the presence of an impaired negative feedback. The activation pattern present in schizophrenia may explain the reduced ability to appropriately contextualize past experiences shown by individuals with psychosis in social stressful situation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Psychological Stress and the Cutaneous Immune Response: Roles of the HPA Axis and the Sympathetic Nervous System in Atopic Dermatitis and Psoriasis

    Directory of Open Access Journals (Sweden)

    Jessica M. F. Hall

    2012-01-01

    Full Text Available Psychological stress, an evolutionary adaptation to the fight-or-flight response, triggers a number of physiological responses that can be deleterious under some circumstances. Stress signals activate the hypothalamus-pituitary-adrenal (HPA axis and the sympathetic nervous system. Elements derived from those systems (e.g., cortisol, catecholamines and neuropeptides can impact the immune system and possible disease states. Skin provides a first line of defense against many environmental insults. A number of investigations have indicated that the skin is especially sensitive to psychological stress, and experimental evidence shows that the cutaneous innate and adaptive immune systems are affected by stressors. For example, psychological stress has been shown to reduce recovery time of the stratum corneum barrier after its removal (innate immunity and alters antigen presentation by epidermal Langerhans cells (adaptive immunity. Moreover, psychological stress may trigger or exacerbate immune mediated dermatological disorders. Understanding how the activity of the psyche-nervous -immune system axis impinges on skin diseases may facilitate coordinated treatment strategies between dermatologists and psychiatrists. Herein, we will review the roles of the HPA axis and the sympathetic nervous system on the cutaneous immune response. We will selectively highlight how the interplay between psychological stress and the immune system affects atopic dermatitis and psoriasis.

  11. Stressed lungs: unveiling the role of circulating stress hormones in ozone-induced lung injury and inflammation

    Science.gov (United States)

    Our recent work demonstrated that circulating stress hormones, epinephrine and corticosterone/cortisol, are involved in mediating ozone pulmonary effects through the activation of hypothalamus-pituitary-adrenal (HPA) axis. Adrenalectomy in Wistar Kyoto (WKY) rats diminished circu...

  12. Boosting recovery rather than buffering reactivity: Higher stress-induced oxytocin secretion is associated with increased cortisol reactivity and faster vagal recovery after acute psychosocial stress.

    Science.gov (United States)

    Engert, Veronika; Koester, Anna M; Riepenhausen, Antje; Singer, Tania

    2016-12-01

    Animal models and human studies using paradigms designed to stimulate endogenous oxytocin release suggest a stress-buffering role of oxytocin. We here examined the involvement of stress-induced peripheral oxytocin secretion in reactivity and recovery phases of the human psychosocial stress response. Healthy male and female participants (N=114) were subjected to a standardized laboratory stressor, the Trier Social Stress Test. In addition to plasma oxytocin, cortisol was assessed as a marker of hypothalamic-pituitary-adrenal (HPA-) axis activity, alpha-amylase and heart rate as markers of sympathetic activity, high frequency heart rate variability as a marker of vagal tone and self-rated anxiety as an indicator of subjective stress experience. On average, oxytocin levels increased by 51% following psychosocial stress. The stress-induced oxytocin secretion, however, did not reduce stress reactivity. To the contrary, higher oxytocin secretion was associated with greater cortisol reactivity and peak cortisol levels in both sexes. In the second phase of the stress response the opposite pattern was observed, with higher oxytocin secretion associated with faster vagal recovery. We suggest that after an early stage of oxytocin and HPA-axis co-activation, the stress-reducing action of oxytocin unfolds. Due to the time lag it manifests as a recovery-boosting rather than a reactivity-buffering effect. By reinforcing parasympathetic autonomic activity, specifically during stress recovery, oxytocin may provide an important protective function against the health-compromising effects of sustained stress. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Calcium, parathyroid hormone, oxytocin and pH profiles in the whelping bitch.

    Science.gov (United States)

    Hollinshead, F K; Hanlon, D W; Gilbert, R O; Verstegen, J P; Krekeler, N; Volkmann, D H

    2010-06-01

    Despite the high prevalence of primary uterine inertia in whelping bitches, the underlying pathogenesis remains unclear. The objectives were to i) determine serum concentrations of total calcium, ionized calcium (iCa), parathyroid hormone (PTH), and blood pH in normally whelping bitches throughout the peri-parturient period; and ii) investigate relationships among iCa, PTH, and acid-base status, and the role that they and oxytocin may have in the underlying pathogenesis of canine uterine inertia. Bitches were randomly selected from a population of German Shepherd Dog bitches with a history of uncomplicated parturition (Group 1; n=10), and from a population of Labrador bitches with a clinical history of an increased incidence of uterine inertia and stillbirths (Group 2; n=20). Jugular blood samples were collected daily from -4 d to the onset of whelping (t=0 h), and then every 4h until the last pup was born. Overall, bitches from Group 2 had higher mean+/-SEM serum concentrations of PTH (4.72+/-2.45 pmol/L, P<0.001), lower iCa (1.31+/-0.08 pmol/L, P<0.05), and higher venous pH (7.41+/-0.03, P<0.005) than bitches from Group 1 (2.9+/-1.44 pmol/L, 1.38+/-0.06 mmol/L, and 7.33+/-0.02, respectively) during the periparturient period. However, there was no significant difference between Groups 1 and 2 for serum oxytocin concentrations during the periparturient period (45.5+/-40 and 65.5+/-82 pg/mL). We inferred that low iCa resulting from a rising pH and decreasing PTH during the periparturient period may have contributed to decreased uterine contractility and increased risk of stillbirths. Therefore, manipulating the cationic/anionic difference in diets of pregnant bitches, similar to the bovine model for hypocalcamia, may reduce the incidence of stillbirths in the bitch. 2010 Elsevier Inc. All rights reserved.

  14. The interaction of BDNF Val66Met, PTSD, and child abuse on psychophysiological reactivity and HPA axis function in a sample of Gulf War Veterans.

    Science.gov (United States)

    Young, Dmitri A; Neylan, Thomas C; O'Donovan, Aoife; Metzler, Thomas; Richards, Anne; Ross, Jessica A; Inslicht, Sabra S

    2018-08-01

    While the BDNF Val66Met polymorphism has been linked to various psychological disorders, limited focus has been on its relationship to posttraumatic stress disorder (PTSD) and early traumas such as child abuse. Therefore, we assessed whether Val66Met was associated with fear potentiated psychophysiological response and HPA axis dysfunction and whether PTSD status or child abuse history moderated these outcomes in a sample of Veterans. 226 and 173 participants engaged in a fear potentiated acoustic startle paradigm and a dexamethasone suppression test (DST) respectively. Fear conditions included no, ambiguous, and high threat conditions. Psychophysiological response measures included electromyogram (EMG), skin conductance response (SCR), and heart rate. The Clinician Administered PTSD Scale (CAPS) and the Trauma History Questionnaire (THQ) were used to assess PTSD status and child abuse history respectively. Met allele carriers exhibited greater SCR magnitudes in the no and ambiguous threat conditions (p < 0.01 and p < 0.05 respectively). Met carriers with PTSD exhibited greater physiological response magnitudes in the ambiguous (SCR, p < 0.001) and high threat conditions (SCR and heart rate, both p ≤ 0.005). Met carrier survivors of child abuse exhibited blunted heart rate magnitudes in the high threat condition (p < 0.01). Met allele carries with PTSD also exhibited greater percent cortisol suppression (p < 0.005). Limitations included small sample size and the cross-sectional nature of the data. The Val66met may impact PTSD susceptibility differentially via enhanced threat sensitivity and HPA axis dysregulation. Child abuse may moderate Val66Met's impact on threat reactivity. Future research should explore how neuronal mechanisms might mediate this risk. Published by Elsevier B.V.

  15. Piper sarmentosum Roxb. produces antidepressant-like effects in rodents, associated with activation of the CREB-BDNF-ERK signaling pathway and reversal of HPA axis hyperactivity.

    Science.gov (United States)

    Li, Qing; Qu, Fa-Lin; Gao, Yue; Jiang, Yi-Ping; Rahman, Khalid; Lee, Kuo-Hsiung; Han, Ting; Qin, Lu-Ping

    2017-03-06

    There are many plants of genus Piper which have been reported to induce antidepressant-like effects, Piper sarmentosum (PS) is one of them. PS is a Chinese herbal medicine and a traditional edible vegetable. In the present study, the antidepressant-like effects of PS extracts and the ethyl acetate fraction of PS extracts (PSY) were assessed using the open field test (OFT), forced swimming test (FST), and tail suspension test (TST) in mice. Furthermore, we applied a 4 consecutive weeks of chronic unpredictable mild stress (CUMS) as a model of depression in rats, followed by a sucrose preference test. Then we examined the possible mechanisms of this action. The activity of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by detecting the serum corticosterone (CORT) concentrations, and the protein expression levels of brain-derived neurotrophic factor (BDNF), the phosphorylated form CREB and ERK1/2 were detected by qRT-PCR or Western blot. The results showed that PS extracts (100, 200mg/kg) and PSY (12.5, 25, 50mg/kg) treatment produced antidepressant-like effects in mice similar to fluoxetine (20mg/kg), indicated by the reduced immobility time in the FST and TST, while both had no influence on the locomotor activity in the OFT. PSY treatment significantly increased sucrose preference and reduced serum CORT levels in CUMS rats. Moreover, PSY up-regulated BDNF protein levels, and increased CREB and ERK phosphorylation levels in the hippocampus on CUMS rats. These findings suggest that the antidepressant-like effects of PS extracts and PSY are mediated, at least in part, by modulating HPA axis, BDNF, CREB and ERK phosphorylation and expression in the hippocampus. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  16. Patient-specific modeling of the neuroendocrine HPA-axis and its relation to depression: Ultradian and circadian oscillations

    DEFF Research Database (Denmark)

    Gudmand-Høyer, Johanne; Ottesen, Stine Timmermann; Ottesen, Johnny T.

    2014-01-01

    underlying physiological mechanisms controlling the average levels as well as the ultradian frequencies and amplitudes of the hormones ACTH and cortisol. The results are promising since they point toward an exact etiology for depression. As a consequence new biomarkers and pharmaceutical targets may...

  17. Levels of central oxytocin and glucocorticoid receptor and serum adrenocorticotropic hormone and corticosterone in mandarin voles with different levels of sociability.

    Science.gov (United States)

    Qiao, Xufeng; Yan, Yating; Tai, Fadao; Wu, Ruiyong; Hao, Ping; Fang, Qianqian; Zhang, Shuwei

    2014-11-01

    Sociability is the prerequisite to social living. Oxytocin and the hypothalamo-pituitary-adrenocortical axis mediate various social behaviors across different social contexts in different rodents. We hypothesized that they also mediate levels of non-reproductive social behavior. Here we explored naturally occurring variation in sociability through a social preference test and compared central oxytocin, glucocorticoid receptors, serum adrenocorticotropic hormone and corticosterone in mandarin voles with different levels of sociability. We found that low-social voles showed higher levels of anxiety-like behavior in open field tests, and had more serum adrenocorticotropic hormone and corticosterone than high-social voles. High-social individuals had more glucocorticoid receptor positive neurons in the hippocampus and more oxytocin positive neurons in the paraventricular nuclei and supraoptic nuclei of the hypothalamus than low-social individuals. Within the same level of sociability, females had more oxytocin positive neurons in the paraventricular nuclei and supraoptic nuclei of the hypothalamus than males. These results indicate that naturally occurring social preferences are associated with higher levels of central oxytocin and hippocampus glucocorticoid receptor and lower levels of anxiety and serum adrenocorticotropic hormone and corticosterone. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Molecular evolution of the neurohypophysial hormone precursors in mammals: Comparative genomics reveals novel mammalian oxytocin and vasopressin analogues.

    Science.gov (United States)

    Wallis, Michael

    2012-11-01

    Among vertebrates the neurohypophysial hormones show considerable variation. However, in eutherian mammals they have been considered rather conserved, with arginine vasopressin (AVP) and oxytocin (OT) in all species except pig and some relatives, where lysine vasopressin replaces AVP. The availability of genomic data for a wide range of mammals makes it possible to assess whether these peptides and their precursors may be more variable in Eutheria than previously suspected. A survey of these data confirms that AVP and OT occur in most eutherians, but with exceptions. In a New-World monkey (marmoset, Callithrix jacchus) and in tree shrew (Tupaia belangeri), Pro(8)OT replaces OT, confirming a recent report for these species. In armadillo (Dasypus novemcinctus) Leu(3)OT replaces OT, while in tenrec (Echinops telfairi) Thr(4)AVP replaces AVP. In these two species there is also evidence for additional genes/pseudogenes, encoding much-modified forms of AVP, but in most other eutherian species there is no evidence for additional neurohypophysial hormone genes. Evolutionary analysis shows that sequences of eutherian neurohypophysial hormone precursors are generally strongly conserved, particularly those regions encoding active peptide and neurophysin. The close association between OT and VP genes has led to frequent gene conversion of sequences encoding neurophysins. A monotreme, platypus (Ornithorhynchus anatinus) has genes for OT and AVP, organized tail-to-tail as in eutherians, but in marsupials 3-4 genes are present for neurohypophysial hormones, organized tail-to-head as in lower vertebrates. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Blunting of the HPA-axis underlies the lack of preventive efficacy of early post-stressor single-dose Delta-9-tetrahydrocannabinol (THC).

    Science.gov (United States)

    Mayer, Tzur Alexander; Matar, Michael Alex; Kaplan, Zeev; Zohar, Joseph; Cohen, Hagit

    2014-07-01

    The therapeutic value of Delta-9-tetrahydrocannabinol (Δ9-THC) in the aftermath of trauma has recently raised interest. A prospective animal model for posttraumatic stress disorder was employed to assess the behavioral effects of a single dose of Δ9-THC administered intraperitoneally following exposure to psychogenic stress. Animals were exposed to predator scent stress and treated 1h later with Δ9-THC (1, 5 and 10mg/kg) or vehicle. The outcome measures included behavior in an elevated plus-maze and acoustic startle response 1, 6 and 24 h or 7 days after exposure and freezing behavior upon exposure to a trauma cue on day 8. Pre-set cut-off behavioral criteria classified exposed animals as those with "extreme," "minimal" or "intermediate" (partial) response. Circulating corticosterone levels were assessed over 2h after exposure with and without Δ9-THC. The behavioral effects of a CB1 antagonist (AM251) administered systemically 1h post exposure were evaluated. In the short term (1-6 h), 5 mg/kg of Δ9-THC effectively attenuated anxiety-like behaviors. In the longer-term (7 days), it showed no effect in attenuating PTSD-like behavioral stress responses, or freezing response to trauma cue. Δ9-THC significantly decreased corticosterone levels. In contrast, administration of AM251 (a CB1 antagonist/inverse agonist) 1 h post exposure attenuated long-term behavioral stress responses through activation of the HPA-axis. The demonstrated lack of preventive efficacy of early Δ9-THC treatment and reports of its anxiogenic effects in many individuals raises doubts not only regarding its potential clinical value, but also the advisability of clinical trials. The endocannabinoids exert complex effects on behavioral responses mediating glucocorticoid effects on memory of traumatic experiences. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Activation of the HPA axis and depression of feeding behavior induced by restraint stress are separately regulated by PACAPergic neurotransmission in the mouse.

    Science.gov (United States)

    Jiang, Sunny Zhihong; Eiden, Lee E

    2016-07-01

    We measured serum CORT elevation in wild-type and PACAP-deficient C57BL/6N male mice after acute (1 h) or prolonged (2-3 h) daily restraint stress for 7 d. The PACAP dependence of CORT elevation was compared to that of stress-induced hypophagia. Daily restraint induced unhabituated peak CORT elevation, and hypophagia/weight loss, of similar magnitude for 1, 2, and 3 h of daily restraint, in wild-type mice. Peak CORT elevation, and hypophagia, were both attenuated in PACAP-deficient mice for 2 and 3 h daily restraint. Hypophagia induced by 1-h daily restraint was also greatly reduced in PACAP-deficient mice, however CORT elevation, both peak and during recovery from stress, was unaffected. Thus, hypothalamic PACAPergic neurotransmission appears to affect CRH gene transcription and peptide production, but not CRH release, in response to psychogenic stress. A single exposure to restraint sufficed to trigger hypophagia over the following 24 h. PACAP deficiency attenuated HPA axis response (CORT elevation) to prolonged (3 h) but not acute (1 h) single-exposure restraint stress, while hypophagia induced by either a single 1 h or a single 3 h restraint were both abolished in PACAP-deficient mice. These results suggest that PACAP's actions to promote suppression of food intake following an episode of psychogenic stress is unrelated to the release of CRH into the portal circulation to activate the pituitary-adrenal axis. Furthermore, demonstration of suppressed food intake after a single 1-h restraint stress provides a convenient assay for investigating the location of the synapses and circuits mediating the effects of PACAP on the behavioral sequelae of psychogenic stress.

  1. [Role of the Periaqueductal Gray Matter of the Midbrain in Regulation of Somatic Pain Sensitivity During Stress: Participation of Corticotropin-Releasing Factor and Glucocorticoid Hormones].

    Science.gov (United States)

    Yarushkina, N I; Filaretova, L P

    2015-01-01

    Periaqueductal gray matter of the midbrain (PAGM) plays a crucial role in the regulation of pain sensitivity under stress, involving in the stress-induced analgesia. A key hormonal system of adaptation under stress is the hypothalamic-pituitary-adrenocortical (HPA) axis. HPA axis's hormones, corticotropin-releasing factor (CRF) and glucocorticoids, are involved in stress-induced analgesia. Exogenous hormones of the HPA axis, similarly to the hormones produced under stress, may cause an analgesic effect. CRF-induced analgesia may be provided by glucocorticoid hormones. CRF and glucocorticoids-induced effects on somatic pain sensitivity may be mediated by PAGM. The aim of the review was to analyze the data of literature on the role of PAGM in the regulation of somatic pain sensitivity under stress and in providing of CRF and glucocorticoid-induced analgesia.

  2. Oxytocin, vasopressin, prostaglandin F(2alpha), luteinizing hormone, testosterone, estrone sulfate, and cortisol plasma concentrations after sexual stimulation in stallions.

    Science.gov (United States)

    Veronesi, M C; Tosi, U; Villani, M; Govoni, N; Faustini, M; Kindahl, H; Madej, A; Carluccio, A

    2010-03-01

    This experiment was designed to determine the effects of sexual stimulation on plasma concentrations of oxytocin (OT), vasopressin (VP), 15-ketodihydro-PGF(2alpha) (PG-metabolite), luteinizing hormone (LH), testosterone (T), estrone sulfate (ES), and cortisol (C) in stallions. Semen samples were collected from 14 light horse stallions (Equus caballus) of proven fertility using a Missouri model artificial vagina. Blood samples were collected at 15, 12, 9, 6, and 3 min before estrous mare exposure, at erection, at ejaculation, and at 3, 6, and 9 min after ejaculation. Afterwards, blood sampling was performed every 10 min for the following 60 min. Sexual activity determined an increase in plasma concentrations of OT, VP, C, PG-metabolite, and ES and caused no changes in LH and T concentrations. The finding of a negative correlation between C and VP at erection, and between C and T before erection and at the time of erection, could be explained by a possible inhibitory role exerted by C in the mechanism of sexual arousal described for men. Copyright 2010 Elsevier Inc. All rights reserved.

  3. A meta-analytic review of the impact of intranasal oxytocin administration on cortisol concentrations during laboratory tasks: moderation by method and mental health.

    Science.gov (United States)

    Cardoso, Christopher; Kingdon, Danielle; Ellenbogen, Mark A

    2014-11-01

    A large body of research has examined the acute effects of intranasal oxytocin administration on social cognition and stress-regulation. While progress has been made with respect to understanding the effect of oxytocin administration on social cognition in clinical populations (e.g. autism, schizophrenia), less is known about its impact on the functioning of the hypothalamic-pituitary-adrenal (HPA) axis among individuals with a mental disorder. We conducted a meta-analysis on the acute effect of intranasal oxytocin administration on the cortisol response to laboratory tasks. The search yielded eighteen studies employing a randomized, placebo-controlled design (k=18, N=675). Random-effects models and moderator analyses were performed using the metafor package for the statistical program R. The overall effect size estimate was modest and not statistically significant (Hedges g=-0.151, p=0.11) with moderate heterogeneity in this effect across studies (I(2)=31%). Controlling for baseline differences in cortisol concentrations, moderation analyses revealed that this effect was larger in response to challenging laboratory tasks that produced a robust stimulation of the HPA-axis (Hedges g=-0.433, 95% CI[-0.841, -0.025]), and in clinical populations relative to healthy controls (Hedges g=-0.742, 95% CI[-1.405, -0.078]). Overall, oxytocin administration showed greater attenuation of the cortisol response to laboratory tasks that strongly activated the HPA-axis, relative to tasks that did not. The effect was more robust among clinical populations, suggesting possible increased sensitivity to oxytocin among those with a clinical diagnosis and concomitant social difficulties. These data support the view that oxytocin may play an important role in HPA dysfunction associated with psychopathology. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. BDNF and glucocorticoids regulate corticotrophin-releasing hormone (CRH) homeostasis in the hypothalamus.

    Science.gov (United States)

    Jeanneteau, Freddy D; Lambert, W Marcus; Ismaili, Naima; Bath, Kevin G; Lee, Francis S; Garabedian, Michael J; Chao, Moses V

    2012-01-24

    Regulation of the hypothalamic-pituitary-adrenal (HPA) axis is critical for adaptation to environmental changes. The principle regulator of the HPA axis is corticotrophin-releasing hormone (CRH), which is made in the parventricular nucleus and is an important target of negative feedback by glucocorticoids. However, the molecular mechanisms that regulate CRH are not fully understood. Disruption of normal HPA axis activity is a major risk factor of neuropsychiatric disorders in which decreased expression of the glucocorticoid receptor (GR) has been documented. To investigate the role of the GR in CRH neurons, we have targeted the deletion of the GR, specifically in the parventricular nucleus. Impairment of GR function in the parventricular nucleus resulted in an enhancement of CRH expression and an up-regulation of hypothalamic levels of BDNF and disinhibition of the HPA axis. BDNF is a stress and activity-dependent factor involved in many activities modulated by the HPA axis. Significantly, ectopic expression of BDNF in vivo increased CRH, whereas reduced expression of BDNF, or its receptor TrkB, decreased CRH expression and normal HPA functions. We find the differential regulation of CRH relies upon the cAMP response-element binding protein coactivator CRTC2, which serves as a switch for BDNF and glucocorticoids to direct the expression of CRH.

  5. Blunted cortisol response after administration of corticotropin releasing hormone in endotoxemic dogs

    NARCIS (Netherlands)

    Moeniralam, H. S.; Endert, E.; van Lanschot, J. J.; Sauerwein, H. P.; Romijn, J. A.

    1997-01-01

    To evaluate the effects of a standard inflammatory challenge on the dynamics of the hypothalamic-pituitary-adrenal (HPA) axis, we studied the effects of low-dose endotoxin (1.0 microgram/kg) on plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations in a saline-controlled study in five

  6. Sex, stress, and mood disorders: at the intersection of adrenal and gonadal hormones.

    Science.gov (United States)

    Fernández-Guasti, A; Fiedler, J L; Herrera, L; Handa, R J

    2012-07-01

    The risk for neuropsychiatric illnesses has a strong sex bias, and for major depressive disorder (MDD), females show a more than 2-fold greater risk compared to males. Such mood disorders are commonly associated with a dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis. Thus, sex differences in the incidence of MDD may be related with the levels of gonadal steroid hormone in adulthood or during early development as well as with the sex differences in HPA axis function. In rodents, organizational and activational effects of gonadal steroid hormones have been described for the regulation of HPA axis function and, if consistent with humans, this may underlie the increased risk of mood disorders in women. Other developmental factors, such as prenatal stress and prenatal overexposure to glucocorticoids can also impact behaviors and neuroendocrine responses to stress in adulthood and these effects are also reported to occur with sex differences. Similarly, in humans, the clinical benefits of antidepressants are associated with the normalization of the dysregulated HPA axis, and genetic polymorphisms have been found in some genes involved in controlling the stress response. This review examines some potential factors contributing to the sex difference in the risk of affective disorders with a focus on adrenal and gonadal hormones as potential modulators. Genetic and environmental factors that contribute to individual risk for affective disorders are also described. Ultimately, future treatment strategies for depression should consider all of these biological elements in their design. © Georg Thieme Verlag KG Stuttgart · New York.

  7. Newborn Analgesia Mediated by Oxytocin during Delivery

    Science.gov (United States)

    Mazzuca, Michel; Minlebaev, Marat; Shakirzyanova, Anastasia; Tyzio, Roman; Taccola, Giuliano; Janackova, Sona; Gataullina, Svetlana; Ben-Ari, Yehezkel; Giniatullin, Rashid; Khazipov, Rustem

    2011-01-01

    The mechanisms controlling pain in newborns during delivery are poorly understood. We explored the hypothesis that oxytocin, an essential hormone for labor and a powerful neuromodulator, exerts analgesic actions on newborns during delivery. Using a thermal tail-flick assay, we report that pain sensitivity is two-fold lower in rat pups immediately after birth than 2 days later. Oxytocin receptor antagonists strongly enhanced pain sensitivity in newborn, but not in 2-day-old rats, whereas oxytocin reduced pain at both ages suggesting an endogenous analgesia by oxytocin during delivery. Similar analgesic effects of oxytocin, measured as attenuation of pain-vocalization induced by electrical whisker pad stimulation, were also observed in decerebrated newborns. Oxytocin reduced GABA-evoked calcium responses and depolarizing GABA driving force in isolated neonatal trigeminal neurons suggesting that oxytocin effects are mediated by alterations of intracellular chloride. Unlike GABA signaling, oxytocin did not affect responses mediated by P2X3 and TRPV1 receptors. In keeping with a GABAergic mechanism, reduction of intracellular chloride by the diuretic NKCC1 chloride co-transporter antagonist bumetanide mimicked the analgesic actions of oxytocin and its effects on GABA responses in nociceptive neurons. Therefore, endogenous oxytocin exerts an analgesic action in newborn pups that involves a reduction of the depolarizing action of GABA on nociceptive neurons. Therefore, the same hormone that triggers delivery also acts as a natural pain killer revealing a novel facet of the protective actions of oxytocin in the fetus at birth. PMID:21519396

  8. Distress calls of the greater short-nosed fruit bat Cynopterus sphinx activate hypothalamic-pituitary-adrenal (HPA) axis in conspecifics.

    Science.gov (United States)

    Mariappan, Subramanian; Bogdanowicz, Wieslaw; Marimuthu, Ganapathy; Rajan, Koilmani Emmanuvel

    2013-09-01

    In a stressful situation, greater short-nosed fruit bats (Cynopterus sphinx) emit audible vocalization either to warn or to inform conspecifics. We examined the effect of distress calls on bats emitting the call as well as the bats receiving the distress signal through analysis of the hypothalamic-pituitary-adrenal axis and catacholaminargic systems. We measured the levels of neurotransmitters [serotonin (5-HT), dopamine (DA), norepinephrine (NE)] and stress hormones [(adrenocorticotropic hormone (ACTH) and corticosterone (CORT)]. Our results showed that distress call emission elevated the level of ACTH and CORT, as well as 5-HT, DA and NE in the amygdala, for both the call emitting bat and the responding bat. Subsequently, we observed increased activity of glucocorticoid receptor and its steroid receptor co-activator (SRC-1). An expression of SRC-1 was up-regulated in the distress call emitter only, whereas it was at a similar level in both the call responder and silent bats. These findings suggest that bats emitting distress calls and also bats responding to such calls have similar neurotransmitter expression patterns, and may react similarly in response to stress.

  9. Hypothalamic-pituitary-adrenal axis response to acute psychosocial stress: Effects of biological sex and circulating sex hormones.

    Science.gov (United States)

    Stephens, Mary Ann C; Mahon, Pamela B; McCaul, Mary E; Wand, Gary S

    2016-04-01

    Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis influences the risk for developing stress-related disorders. Sex-dependent differences in the HPA axis stress response are believed to contribute to the different prevalence rates of stress-related disorders found in men and women. However, studies examining the HPA axis stress response have shown mixed support for sex differences, and the role of endogenous sex hormones on HPA axis response has not been adequately examined in humans. This study utilized the largest sample size to date to analyze the effects of biological sex and sex hormones on HPA axis social stress responses. Healthy, 18- to 30- year-old community volunteers (N=282) completed the Trier Social Stress Test (TSST), a widely used and well-validated stress-induction laboratory procedure. All women (n=135) were tested during the follicular phase of their menstrual cycle (when progesterone levels are most similar to men). Adrenocorticotropic hormone (ACTH) and cortisol measures were collected at multiple points throughout pre- and post-TSST. Testosterone and progesterone (in men) and progesterone and estradiol (in women) were determined pre-TSST. Following the TSST, men had greater ACTH and cortisol levels than women. Men had steeper baseline-to-peak and peak-to-end ACTH and cortisol response slopes than women; there was a trend for more cortisol responders among men than women. Testosterone negatively correlated with salivary cortisol response in men, while progesterone negatively correlated with ACTH and cortisol responses in women. These data confirm that men show more robust activation of the HPA axis response to the TSST than do women in the follicular phase of the menstrual cycle. Testosterone results suggest an inhibitory effect on HPA axis reactivity in men. Progesterone results suggest an inhibitory effect on HPA axis reactivity in women. Future work is needed to explain why men mount a greater ACTH and cortisol response to the

  10. The non-peptide CRH1-antagonist CP-154,526 elicits a paradoxical route-dependent activation of the HPA axis.

    Science.gov (United States)

    Zaretsky, Dmitry V; Zaretskaia, Maria V; Sarkar, Sumit; Rusyniak, Daniel E; DiMicco, Joseph A

    2017-07-13

    The corticotropin-releasing hormone (CRH) plays an important role in mediating physiological response to stress and is thought to be involved in the development of various psychiatric disorders. In this paper, we compare the differences between the effect of intraperitoneal (i.p.) and intraarterial (i.a.) administration of the non-peptide CRH 1 antagonist CP-154,526 (CP) (10 and 20mg/kg) on plasma adrenocorticotropic hormone levels (ACTH), heart rate, MAP, and c-Fos expression in the paraventricular nucleus of the hypothalamus. Intraperitoneal, but not i.a., injection of CP resulted in an increase in plasma ACTH (from 105±13 to 278±51pg/ml after 20mg/kg). This effect was accompanied by a dramatic increase in c-Fos expression in cells immunoreactive for CRH in the paraventricular nucleus of the hypothalamus. When the drug was administered i.p., CP-induced activation of the HPA appears to mask the inhibitory effect of CP on stress-induced ACTH secretion, an effect which was readily apparent when the drug was given i.a. Intraperitoneal administration of CP also increased the baseline MAP which may account for previous reports that treatment with this drug attenuated the increases associated with stress. CP given by either route had no effect on baseline heart rate or stress-induced tachycardia. Thus, in all studies in which CP 154,526 is given, the route of delivery must be given careful consideration. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Enriched environment influences hormonal status and hippocampal brain derived neurotrophic factor in a sex dependent manner.

    Science.gov (United States)

    Bakos, J; Hlavacova, N; Rajman, M; Ondicova, K; Koros, C; Kitraki, E; Steinbusch, H W M; Jezova, D

    2009-12-01

    The present study is aimed at testing the hypothesis that an enriched environment (EE) induces sex-dependent changes in stress hormone release and in markers of increased brain plasticity. The focus was on hypothalamic-pituitary-adrenocortical (HPA) axis activity, plasma levels of stress hormones, gene expression of glutamate receptor subunits and concentrations of brain-derived neurotrophic factor (BDNF) in selected brain regions. Rats exposed to EE were housed in groups of 12 in large cages with various objects, which were frequently changed, for 6 weeks. Control animals were housed four per cage under standard conditions. In females the EE-induced rise in hippocampal BDNF, a neurotrophic factor associated with increased neural plasticity, was more pronounced than in males. Similar sex-specific changes were observed in BDNF concentrations in the hypothalamus. EE also significantly attenuated oxytocin and aldosterone levels only in female but not male rats. Plasma testosterone positively correlated with hippocampal BDNF in female but not male rats housed in EE. In male rats housing in EE led to enhanced levels of testosterone and adrenocorticotropic hormone (ACTH), this was not seen in females. Hippocampal glucocorticoid but not mineralocorticoid receptor levels decreased in rats housed in EE irrespective of sex. Housing conditions failed to modify mRNA levels of glutamate receptor type 1 (Glur1) and metabotropic glutamate receptor subtype 5 (mGlur5) subunits of glutamate receptors in the forebrain. Moreover, a negative association between corticosterone and BDNF was observed in both sexes. The results demonstrate that the association between hormones and changes in brain plasticity is sex related. In particular, testosterone seems to be involved in the regulatory processes related to neuroplasticity in females.

  12. Blunted neuroactive steroid and HPA axis responses to stress are associated with reduced sleep quality and negative affect in pregnancy: a pilot study.

    Science.gov (United States)

    Crowley, Shannon K; O'Buckley, Todd K; Schiller, Crystal E; Stuebe, Alison; Morrow, A Leslie; Girdler, Susan S

    2016-04-01

    Anxiety during pregnancy has been linked to adverse maternal health outcomes, including postpartum depression (PPD). However, there has been limited study of biological mechanisms underlying behavioral predictors of PPD during pregnancy. Considering the shared etiology of chronic stress amongst antenatal behavioral predictors, the primary goal of this pilot study was to examine associations among stress-related physiological factors (including GABA-ergic neurosteroids) and stress-related behavioral indices of anxiety during pregnancy. Fourteen nulliparous women in their second trimester of a singleton pregnancy underwent speech and mental arithmetic stress, following a 2-week subjective and objective recording of sleep-wake behavior. Lower cortisol, progesterone, and a combined measure of ALLO + pregnanolone throughout the entire stressor protocol (area under the curve, AUC) were associated with greater negative emotional responses to stress, and lower cortisol AUC was associated with worse sleep quality. Lower adrenocorticotropic hormone was associated with greater anxious and depressive symptoms. Stress produced paradoxical reductions in cortisol, progesterone, and a combined measure of allopregnanolone + pregnanolone, while tetrahydrodeoxycorticosterone levels were elevated. These data suggest that cortisol, progesterone, and ALLO + pregnanolone levels in the second trimester of pregnancy are inversely related to negative emotional symptoms, and the negative impact of acute stress challenge appears to exert its effects by reducing these steroids to further promote negative emotional responses.

  13. Sex differences between CRF1 receptor deficient mice following naloxone-precipitated morphine withdrawal in a conditioned place aversion paradigm: implication of HPA axis.

    Directory of Open Access Journals (Sweden)

    Juan-Antonio García-Carmona

    Full Text Available Extinction period of positive affective memory of drug taking and negative affective memory of drug withdrawal, as well as the different response of men and women might be important for the clinical treatment of drug addiction. We investigate the role of corticotropin releasing factor receptor type one (CRF1R and the different response of male and female mice in the expression and extinction of the aversive memory.We used genetically engineered male and female mice lacking functional CRF1R. The animals were rendered dependent on morphine by intraperitoneally injection of increasing doses of morphine (10-60 mg/kg. Negative state associated with naloxone (1 mg/kg s.c.-precipitated morphine withdrawal was examined by using conditioned place aversion (CPA paradigm. No sex differences for CPA expression were found in wild-type (n = 29 or CRF1R knockout (KO mice (n = 29. However, CRF1R KO mice presented less aversion score than wild-type mice, suggesting that CRF1R KO mice were less responsive than wild-type to continuous associations between drug administration and environmental stimuli. In addition, CPA extinction was delayed in wild-type and CRF1R KO male mice compared with females of both genotypes. The genetic disruption of the CRF1R pathway decreased the period of extinction in males and females suggesting that CRF/CRF1R is implicated in the duration of aversive memory. Our results also showed that the increase in adrenocorticotropic hormone (ACTH levels observed in wild-type (n = 11 mice after CPA expression, were attenuated in CRF1R KO mice (n = 10. In addition, ACTH returned to the baseline levels in males and females once CPA extinction was finished.These results suggest that, at least, CPA expression is partially due to an increase in plasma ACTH levels, through activation of CRF1R, which can return when CPA extinction is finished.

  14. Gonadal Steroid Hormones and the Hypothalamo-Pituitary-Adrenal Axis

    OpenAIRE

    Handa, Robert J.; Weiser, Michael J.

    2013-01-01

    The hypothalamo-pituitary-adrenal (HPA) axis represents a complex neuroendocrine feedback loop controlling the secretion of adrenal glucocorticoid hormones. Central to its function is the paraventricular nucleus of the hypothalamus (PVN) where neurons expressing corticotropin releasing factor reside. These HPA motor neurons are a primary site of integration leading to graded endocrine responses to physical and psychological stressors. An important regulatory factor that must be considered, pr...

  15. Stress Hormones and their Regulation in a Captive Dolphin Population

    Science.gov (United States)

    2015-09-30

    out-of- water stress protocol. The observed response to the stress protocol was similar to that of ACTH administrations (see Parent Project for...CD, Booth R, Wasser S, Cotte L, Jensen E, Crocker D, Houser D (2013). The progestin megestrol acetate suppresses the HPA axis in bottlenose dolphin...Kellar, N.M., Cockrem, J., Romano, T., Booth, R.K. and Wasser , S.K. (2015) Natural variation in stress hormones, comparisons across matrices, and

  16. Estrogen receptor β and oxytocin interact to modulate anxiety-like behavior and neuroendocrine stress reactivity in adult male and female rats.

    Science.gov (United States)

    Kudwa, Andrea E; McGivern, Robert F; Handa, Robert J

    2014-04-22

    The hypothalamic-pituitary-adrenal (HPA) axis is activated in response to stressors and is controlled by neurons residing in the paraventricular nucleus of the hypothalamus (PVN). Although gonadal steroid hormones can influence HPA reactivity to stressors, the exact mechanism of action is not fully understood. It is known, however, that estrogen receptor β (ERβ) inhibits HPA reactivity and decreases anxiety-like behavior in rodents. Since ERβ is co-expressed with oxytocin (OT) in neurons of the PVN, an ERβ-selective agonist was utilized to test the whether ERβ decreases stress-induced HPA reactivity and anxiety-like behaviors via an OTergic pathway. Adult gonadectomized male and female rats were administered diarylpropionitrile, or vehicle, peripherally for 5days. When tested for anxiety-like behavior on the elevated plus maze (EPM), diarylpropionitrile-treated males and females significantly increased time on the open arm of the EPM compared to vehicle controls indicating that ERβ reduces anxiety-like behaviors. One week after behavioral evaluation, rats were subjected to a 20minute restraint stress. Treatment with diarylpropionitrile reduced CORT and ACTH responses in both males and females. Subsequently, another group of animals was implanted with cannulae directed at the lateral ventricle. One week later, rats underwent the same protocol as above but with the additional treatment of intracerebroventricular infusion with an OT antagonist (des Gly-NH2 d(CH2)5 [Tyr(Me)(2), Thr(4)] OVT) or VEH, 20min prior to behavioral evaluation. OT antagonist treatment blocked the effects of diarylpropionitrile on the display of anxiety-like behaviors and plasma CORT levels. These data indicate that ERβ and OT interact to modulate the HPA reactivity and the display of anxiety-like behaviors. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Oxytocin Modulates Nociception as an Agonist of Pain-Sensing TRPV1

    Directory of Open Access Journals (Sweden)

    Yelena Nersesyan

    2017-11-01

    Full Text Available Oxytocin is a hormone with various actions. Oxytocin-containing parvocellular neurons project to the brainstem and spinal cord. Oxytocin release from these neurons suppresses nociception of inflammatory pain, the molecular mechanism of which remains unclear. Here, we report that the noxious stimulus receptor TRPV1 is an ionotropic oxytocin receptor. Oxytocin elicits TRPV1 activity in native and heterologous expression systems, regardless of the presence of the classical oxytocin receptor. In TRPV1 knockout mice, DRG neurons exhibit reduced oxytocin sensitivity relative to controls, and oxytocin injections significantly attenuate capsaicin-induced nociception in in vivo experiments. Furthermore, oxytocin potentiates TRPV1 in planar lipid bilayers, supporting a direct agonistic action. Molecular modeling and simulation experiments provide insight into oxytocin-TRPV1 interactions, which resemble DkTx. Together, our findings suggest the existence of endogenous regulatory pathways that modulate nociception via direct action of oxytocin on TRPV1, implying its analgesic effect via channel desensitization.

  18. Emergent synchronous bursting of oxytocin neuronal network.

    Directory of Open Access Journals (Sweden)

    Enrico Rossoni

    2008-07-01

    Full Text Available When young suckle, they are rewarded intermittently with a let-down of milk that results from reflex secretion of the hormone oxytocin; without oxytocin, newly born young will die unless they are fostered. Oxytocin is made by magnocellular hypothalamic neurons, and is secreted from their nerve endings in the pituitary in response to action potentials (spikes that are generated in the cell bodies and which are propagated down their axons to the nerve endings. Normally, oxytocin cells discharge asynchronously at 1-3 spikes/s, but during suckling, every 5 min or so, each discharges a brief, intense burst of spikes that release a pulse of oxytocin into the circulation. This reflex was the first, and is perhaps the best, example of a physiological role for peptide-mediated communication within the brain: it is coordinated by the release of oxytocin from the dendrites of oxytocin cells; it can be facilitated by injection of tiny amounts of oxytocin into the hypothalamus, and it can be blocked by injection of tiny amounts of oxytocin antagonist. Here we show how synchronized bursting can arise in a neuronal network model that incorporates basic observations of the physiology of oxytocin cells. In our model, bursting is an emergent behaviour of a complex system, involving both positive and negative feedbacks, between many sparsely connected cells. The oxytocin cells are regulated by independent afferent inputs, but they interact by local release of oxytocin and endocannabinoids. Oxytocin released from the dendrites of these cells has a positive-feedback effect, while endocannabinoids have an inhibitory effect by suppressing the afferent input to the cells.

  19. The effects of oxytocine in autism : De werking van oxytocine bij autisme

    NARCIS (Netherlands)

    Groen, Yvonne; Althaus, Monika; Oosterhoff, Menno; van Balkom, Ingrid; Hoekstra, Pieter J.

    2017-01-01

    Oxytocin is viewed as the hormone of calm, healing and love, and plays an important role in establishing and maintaining social relationships. As autism is characterized by difficulties in social relationships, a dysregulated oxytocin system could possibly be an underlying factor. Our recently

  20. Salubrious effects of oxytocin on social stress-induced deficits

    Science.gov (United States)

    Smith, Adam S.; Wang, Zuoxin

    2012-01-01

    Social relationships are a fundamental aspect of life, affecting social, psychological, physiological, and behavioral functions. While social interactions can attenuate stress and promote health, disruption, confrontations, isolation, or neglect in the social environment can each be major stressors. Social stress can impair the basal function and stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis, impairing function of multiple biological systems and posing a risk to mental and physical health. In contrast, social support can ameliorate stress-induced physiological and immunological deficits, reducing the risk of subsequent psychological distress and improving an individual's overall well-being. For better clinical treatment of these physiological and mental pathologies, it is necessary to understand the regulatory mechanisms of stress-induced pathologies as well as determine the underlying biological mechanisms that regulate social buffering of the stress system. A number of ethologically relevant animal models of social stress and species that form strong adult social bonds have been utilized to study the etiology, treatment, and prevention of stress-related disorders. While undoubtedly a number of biological pathways contribute to the social buffering of the stress response, the convergence of evidence denotes the regulatory effects of oxytocin in facilitating social bond-promoting behaviors and their effect on the stress response. Thus, oxytocin may be perceived as a common regulatory element of the social environment, stress response, and stress-induced risks on mental and physical health. PMID:22178036

  1. Oxytocin in the Treatment of Dystocia in Mice

    Science.gov (United States)

    Narver, Heather L

    2012-01-01

    Physicians and veterinarians often prescribe oxytocin to treat dystocia. However, oxytocin administration to pregnant women or animals is not without risk. In the venue of laboratory animal medicine, the use of oxytocin may present confounding variables to research. Although oxytocin has been studied extensively, many of its physiologic effects and interactions with other hormones remain unclear. Investigator concerns about adverse and confounding effects of oxytocin in their research mice prompted the current review of oxytocin and its use to treat murine dystocia. Well-controlled studies of oxytocin in dystocic mice have not been conducted. However, in humans and other animals, inconsistent and adverse effects are well-documented. Limited knowledge of the complex physiologic and molecular mechanisms of action of oxytocin and scant support for the efficacy of oxytocin in dystocic mice fail to meet the standards of evidence-based veterinary medical practice. The administration of oxytocin is contraindicated in many cases of dystocia in research mice, and its use in dystocic mice may be unfounded. A brief review of oxytocin and the physiologic mechanisms of parturition are provided to support this conclusion. Alternative treatments for murine dystocia are discussed, and a holistic approach is advocated to better serve animal welfare and to safeguard the integrity of valuable research. Laboratory animal veterinarians overseeing the development of guidelines or standard operating procedures for technician or investigator treatment of dystocic mice should understand the effects of oxytocin administration in light of relevant research. PMID:22330862

  2. Taking the Focus Away from the Self: Low Individualism Mediates the Effect of Oxytocin on Creativity

    Science.gov (United States)

    Pfundmair, Michaela; Frey, Dieter; Hodgson, Timothy L.

    2017-01-01

    Recently, it has been shown that the hormone oxytocin can enable creative cognition. The aim of this investigation was to examine the psychological mechanism via which oxytocin influences creativity. Two opposing explanatory approaches suggested by previous research were investigated: It was predicted that the effect of oxytocin on creativity…

  3. Oxytocin and Estrogen Receptor β in the Brain: An Overview

    Directory of Open Access Journals (Sweden)

    Alexandra eAcevedo-Rodriguez

    2015-10-01

    Full Text Available Oxytocin is a neuropeptide synthesized primarily by neurons of the paraventricular and supraoptic nuclei of the hypothalamus. These neurons have axons that project into the posterior pituitary and release oxytocin into the bloodstream to promote labor and lactation; however, oxytocin neurons also project to other brain areas where it plays a role in numerous brain functions. Oxytocin binds to the widely expressed oxytocin receptor, and, in doing so, it regulates homeostatic processes, social recognition and fear conditioning. In addition to these functions, oxytocin decreases neuroendocrine stress signaling and anxiety-related and depression-like behaviors. Steroid hormones differentially modulate stress responses and alter oxytocin receptor expression. In particular, estrogen receptor β activation has been found to both reduce anxiety-related behaviors and increase oxytocin peptide transcription, suggesting a role for oxytocin in this estrogen receptor β mediated anxiolytic effect. Further research is needed to identify modulators of oxytocin signaling and the pathways utilized and to elucidate molecular mechanisms controlling oxytocin expression to allow better therapeutic manipulations of this system in patient populations.

  4. Oxytocin signaling in the medial amygdala is required for sex discrimination of social cues

    OpenAIRE

    Yao, Shenqin; Bergan, Joseph; Lanjuin, Anne; Dulac, Catherine

    2017-01-01

    eLife digest Oxytocin is a hormone that promotes milk production, contractions during childbirth, and many social interactions in humans and other creatures. It has also been implicated in conditions like autism or schizophrenia, which show altered social interactions. Oxytocin is made and released by cells in the brain called neurons. The oxytocin-producing neurons are clustered in a brain region called the hypothalamus, and oxytocin can act over a long distance in the brain or in the body. ...

  5. Oxytocin is required for nursing but is not essential for parturition or reproductive behavior.

    OpenAIRE

    Nishimori, K; Young, L J; Guo, Q; Wang, Z; Insel, T R; Matzuk, M M

    1996-01-01

    Oxytocin, a neurohypophyseal hormone, has been traditionally considered essential for mammalian reproduction. In addition to uterine contractions during labor and milk ejection during nursing, oxytocin has been implicated in anterior pituitary function, paracrine effects in the testis and ovary and the neural control of maternal and sexual behaviors. To determine the essential role(s) of oxytocin in mammalian reproductive function, mice deficient in oxytocin have been generated using embryoni...

  6. Basal and Adrenocorticotropic Hormone Stimulated Plasma Cortisol Levels Among Egyptian Autistic Children: Relation to Disease Severity

    Directory of Open Access Journals (Sweden)

    Hewedi Doaa H

    2010-10-01

    Full Text Available Abstract Background Autism is a disorder of early childhood characterized by social impairment, communication abnormalities and stereotyped behaviors. The hypothalamic-pituitary-adrenocortical (HPA axis deserves special attention, since it is the basis for emotions and social interactions that are affected in autism. Aim To assess basal and stimulated plasma cortisol, and adrenocorticotropic hormone (ACTH levels in autistic children and their relationship to disease characteristics. Methods Fifty autistic children were studied in comparison to 50 healthy age-, sex- and pubertal stage- matched children. All subjects were subjected to clinical evaluation and measurement of plasma cortisol (basal and stimulated and ACTH. In addition, electroencephalography (EEG and intelligence quotient (IQ assessment were done for all autistic children. Results Sixteen% of autistic patients had high ACTH, 10% had low basal cortisol and 10% did not show adequate cortisol response to ACTH stimulation. Autistic patients had lower basal (p = 0.032 and stimulated cortisol (p = 0.04 and higher ACTH (p = 0.01 than controls. Childhood Autism Rating Scale (CARS score correlated positively with ACTH (r = 0.71, p = 0.02 and negatively with each of basal (r = -0.64, p = 0.04 and stimulated cortisol (r = -0.88, p Conclusions The observed hormonal changes may be due to a dysfunction in the HPA axis in autistic individuals. Further studies are warranted regarding the role of HPA axis dysfunction in the pathogenesis of autism.

  7. Oxytocin in survivors of childhood-onset craniopharyngioma

    NARCIS (Netherlands)

    Daubenbuechel, Anna M. M.; Hoffmann, Anika; Eveslage, Maria; Oezyurt, Jale; Lohle, Kristin; Reichel, Julia; Thiel, Christiane M.; Martens, Henri; Geenen, Vincent; Mueller, Hermann L.

    2016-01-01

    Quality of survival of childhood-onset craniopharyngioma patients is frequently impaired by hypothalamic involvement or surgical lesions sequelae such as obesity and neuropsychological deficits. Oxytocin, a peptide hormone produced in the hypothalamus and secreted by posterior pituitary gland, plays

  8. Oxytocin in survivors of childhood-onset craniopharyngioma

    NARCIS (Netherlands)

    Daubenbuechel, Anna M. M.; Hoffmann, Anika; Eveslage, Maria; Oezyurt, Jale; Lohle, Kristin; Reichel, Julia; Thiel, Christiane M.; Martens, Henri; Geenen, Vincent; Mueller, Hermann L.

    Quality of survival of childhood-onset craniopharyngioma patients is frequently impaired by hypothalamic involvement or surgical lesions sequelae such as obesity and neuropsychological deficits. Oxytocin, a peptide hormone produced in the hypothalamus and secreted by posterior pituitary gland, plays

  9. Effect of Local Vibration and Passive Exercise on the Hormones and Neurotransmitters of Hypothalamic-Pituitary-Adrenal Axis in Hindlimb Unloading Rats

    Science.gov (United States)

    Luan, Huiqin; Huang, Yunfei; Li, Jian; Sun, Lianwen; Fan, Yubo

    2018-04-01

    Astronauts are severely affected by spaceflight-induced bone loss. Mechanical stimulation through exercise inhibits bone resorption and improves bone formation. Exercise and vibration can prevent the degeneration of the musculoskeletal system in tail-suspended rats, and long-term exercise stress will affect endocrine and immune systems that are prone to fatigue. However, the mechanisms through which exercise and vibration affect the endocrine system remain unknown. This study mainly aimed to investigate the changes in the contents of endocrine axis-related hormones and the effects of local vibration and passive exercise on hypothalamic-pituitary-adrenal (HPA) axis-related hormones in tail-suspended rats. A total of 32 Sprague-Dawley rats were randomly distributed into four groups (n = 8 per group): tail suspension (TS), TS + 35Hz vibration, TS + passive exercise, and control. The rats were placed on a passive exercise and local vibration regimen for 21 days. On day 22 of the experiment, the contents of corticotrophin-releasing hormone, adrenocorticotropic hormone, cortisol, and 5-hydroxytryptamine in the rats were quantified with kits in accordance with the manufacturer's instructions. Histomorphometry was applied to evaluate histological changes in the hypothalamus. Results showed that 35Hz local vibration cannot cause rats to remain in a stressed state and that it might not inhibit the function of the HPA axis. Therefore, we speculate that this local vibration intensity can protect the function of the HPA axis and helps tail-suspended rats to transition from stressed to adaptive state.

  10. Mapping the human corticotropin releasing hormone binding protein gene (CRHBP) to the long arm of chromosome 5 (5q11.2-q13.3)

    Energy Technology Data Exchange (ETDEWEB)

    Vamvakopoulos, N.C. [Univ. of Thessaly School of Medicine, Larisa (Greece); Sioutopoulou, T.O. [Univ. of Athens Medical School (Greece); Durkin, S.A. [American Type Culture Collection, Rockville, MD (United States)

    1995-01-01

    Unexpected stimulation or stress activates the heat shock protein (hsp) system at the cellular level and the hypothalamic-pituitary-adrenal (HPA) axis at the level of the whole organism. At the molecular level, these two systems communicate through the functional interaction between hsp90 and glucocorticoid receptor (GR). The corticotropin releasing hormone (CRH) system regulates the mammalian stress response by coordinating the activity of the HPA axis. It consists of the 41-amino-acid-long principal hypothalamic secretagogue for pituitary adrenocorticotropic hormone (ACTH), CRH, its receptor (CRHR), and its binding protein (CRHBP). Because of its central role in the coordination of stress response and whole body homeostasis, the CRH system has been implicated in the pathogenesis of neuroendocrine and psychiatric disease. 19 refs., 1 fig.

  11. Endogenous peripheral oxytocin measures can give insight into the dynamics of social relationships: a review

    Directory of Open Access Journals (Sweden)

    Catherine eCrockford

    2014-03-01

    Full Text Available The neuropeptide, oxytocin, receives increasing attention due to its role in stress regulation and promoting affiliative social behavior. Research across mammals points to a complex pattern whereby social context and individual differences moderate the endogenous release of oxytocin as well as moderate the effects that exogenous administration of oxytocin has on social behavior. In addition to measuring central release of oxytocin or exogenous administration of oxytocin on social behavior, for example via inhalation, it is becoming evident that measuring endogenous peripheral oxytocin levels is an additional, informative tool. This is particularly so when oxytocin can be measured from non-invasively collected samples, such as in urine. Although it is still debated as to whether peripheral measures of oxytocin relate to central measures of oxytocin, anatomical and functional evidence indicate a link between the two. We argue that non-invasive measures of peripheral oxytocin hold several research and potential therapeutic advantages. Principally, study subjects can be sampled repeatedly in different social contexts where social history between interaction partners can be taken into account. Several hormones can be measured simultaneously allowing examination of the influence of oxytocin interactions with other hormones on motivational states. Valence of relationships as well as changes in relationship quality over time can be measured through endocrine responses. Also, the approach of identifying natural social contexts that are associated with endogenous oxytocin release offers the potential of behavioral therapy as an addition or alternative to chemical therapy in the field of mental health.

  12. Neuroendocrine and cardiovascular parameters during simulation of stress-induced rise in circulating oxytocin in the rat.

    Science.gov (United States)

    Ondrejcakova, M; Bakos, J; Garafova, A; Kovacs, L; Kvetnansky, R; Jezova, D

    2010-07-01

    Physiological functions of oxytocin released during stress are not well understood. We have (1) investigated the release of oxytocin during chronic stress using two long-term stress models and (2) simulated stress-induced oxytocin secretion by chronic treatment with oxytocin via osmotic minipumps. Plasma oxytocin levels were significantly elevated in rats subjected to acute immobilization stress for 120 min, to repeated immobilization for 7 days and to combined chronic cold stress exposure for 28 days with 7 days immobilization. To simulate elevation of oxytocin during chronic stress, rats were implanted with osmotic minipumps subcutaneously and treated with oxytocin (3.6 microg/100 g body weight/day) or vehicle for 2 weeks. Chronic subcutaneous oxytocin infusion led to an increase in plasma oxytocin, adrenocorticotropic hormone, corticosterone, adrenal weights and heart/body weight ratio. Oxytocin treatment had no effect on the incorporation of 5-bromo-2-deoxyuridine into DNA in the heart ventricle. Mean arterial pressure response to intravenous phenylephrine was reduced in oxytocin-treated animals. Decrease in adrenal tyrosin hydroxylase mRNA following oxytocin treatment was not statistically significant. Oxytocin treatment failed to modify food intake and slightly increased water consumption. These data provide evidence on increased concentrations of oxytocin during chronic stress. It is possible that the role of oxytocin released during stress is in modulating hypothalamic-pituitary-adrenocortical axis and selected sympathetic functions.

  13. Os efeitos do estresse na função do eixo hipotalâmico-pituitário-adrenal em indivíduos com esquizofrenia The effects of stress on hypothalamic-pituitary-adrenal (HPA axis function in subjects with schizophrenia

    Directory of Open Access Journals (Sweden)

    Francesca L. Guest

    2013-01-01

    Full Text Available Nas últimas décadas, têm surgido evidências sugerindo que a patogênese de desordens psiquiátricas, tais como a esquizofrenia, pode envolver perturbações no eixo hipotalâmico-pituitário-adrenal (HPA. Variações na manifestação desses efeitos poderiam estar relacionadas a diferenças em sintomas clínicos entre os indivíduos afetados, assim como a diferenças na resposta ao tratamento. Tais efeitos podem também ser originados de complexas interações entre genes e fatores ambientais. Aqui, revisamos os efeitos do estresse maternal em anormalidades na regulação do eixo HPA e desenvolvimento de desordens psiquiátricas, incluindo a esquizofrenia. Estudos nessa área podem gerar o aumento do nosso entendimento da natureza multidimensional da esquizofrenia. Posterior pesquisa nesse campo poderia, em última instância, levar ao desenvolvimento de melhores diagnósticos e novas abordagens terapêuticas para essa debilitante condição psiquiátrica.Over the last few decades, evidence has been emerging that the pathogenesis of psychiatric disorders such as schizophrenia can involve perturbations of the hypothalamic-pituitary-adrenal (HPA axis. Variations in the manifestation of these effects could be related to the differences in clinical symptoms between affected individuals as well as to differences in treatment response. Such effects can also arise from the complex interaction between genes and environmental factors. Here, we review the effects of maternal stress on abnormalities in HPA axis regulation and the development of psychiatric disorders including schizophrenia. Studies in this area may prove critical for increasing our understanding of the multi-dimensional nature of schizophrenia. Further research in this area could ultimately lead to the development of improved diagnostics and novel therapeutic approaches for treating this debilitating psychiatric condition.

  14. Hormones

    Science.gov (United States)

    Hormones are your body's chemical messengers. They travel in your bloodstream to tissues or organs. They work ... glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, ...

  15. Activation of presynaptic oxytocin receptors enhances glutamate release in the ventral hippocampus of prenatally restraint stressed rats.

    Science.gov (United States)

    Mairesse, Jérôme; Gatta, Eleonora; Reynaert, Marie-Line; Marrocco, Jordan; Morley-Fletcher, Sara; Soichot, Marion; Deruyter, Lucie; Camp, Gilles Van; Bouwalerh, Hammou; Fagioli, Francesca; Pittaluga, Anna; Allorge, Delphine; Nicoletti, Ferdinando; Maccari, Stefania

    2015-12-01

    Oxytocin receptors are known to modulate synaptic transmission and network activity in the hippocampus, but their precise function has been only partially elucidated. Here, we have found that activation of presynaptic oxytocin receptor with the potent agonist, carbetocin, enhanced depolarization-evoked glutamate release in the ventral hippocampus with no effect on GABA release. This evidence paved the way for examining the effect of carbetocin treatment in "prenatally restraint stressed" (PRS) rats, i.e., the offspring of dams exposed to repeated episodes of restraint stress during pregnancy. Adult PRS rats exhibit an anxious/depressive-like phenotype associated with an abnormal glucocorticoid feedback regulation of the hypothalamus-pituitary-adrenal (HPA) axis, and, remarkably, with a reduced depolarization-evoked glutamate release in the ventral hippocampus. Chronic systemic treatment with carbetocin (1mg/kg, i.p., once a day for 2-3 weeks) in PRS rats corrected the defect in glutamate release, anxiety- and depressive-like behavior, and abnormalities in social behavior, in the HPA response to stress, and in the expression of stress-related genes in the hippocampus and amygdala. Of note, carbetocin treatment had no effect on these behavioral and neuroendocrine parameters in prenatally unstressed (control) rats, with the exception of a reduced expression of the oxytocin receptor gene in the amygdala. These findings disclose a novel function of oxytocin receptors in the hippocampus, and encourage the use of oxytocin receptor agonists in the treatment of stress-related psychiatric disorders in adult life. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Oxytocin and Psychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Gokce Nur Say

    2016-06-01

    Full Text Available Oxytocin is a neuropeptide that plays critical role in mother-infant bonding, pair bonding and prosocial behaviors. Several neuropsychiatric disorders such as autism, schizophrenia, affective disorders, anxiety disorders, attention deficit/hyperactivity disorder, alcohol/substance addiction, aggression, suicide, eating disorders and personality disorders show abnormalities of oxytocin system. These findings have given rise to the studies searching therapeutic use of oxytocin for psychi-atric disorders. The studies of oxytocin interventions in psychiatric disorders yielded potentially promising findings. This paper reviews the role of oxytocin in emotions, behavior and its effects in psychiatric disorders. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2016; 8(2: 102-113

  17. Short circuit: Disaggregation of adrenocorticotropic hormone and cortisol levels in HIV-positive, methamphetamine-using men who have sex with men.

    Science.gov (United States)

    Carrico, Adam W; Rodriguez, Violeta J; Jones, Deborah L; Kumar, Mahendra

    2018-01-01

    This study examined if methamphetamine use alone (METH + HIV-) and methamphetamine use in combination with HIV (METH + HIV+) were associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation as well as insulin resistance relative to a nonmethamphetamine-using, HIV-negative comparison group (METH-HIV-). Using an intact groups design, serum levels of HPA axis hormones in 46 METH + HIV- and 127 METH + HIV+ men who have sex with men (MSM) were compared to 136 METH-HIV- men. There were no group differences in prevailing adrenocorticotropic hormone (ACTH) or cortisol levels, but the association between ACTH and cortisol was moderated by METH + HIV+ group (β = -0.19, p < .05). Compared to METH-HIV- men, METH + HIV+ MSM displayed 10% higher log 10 cortisol levels per standard deviation lower ACTH. Both groups of methamphetamine-using MSM had lower insulin resistance and greater syndemic burden (i.e., sleep disturbance, severe depression, childhood trauma, and polysubstance use disorder) compared to METH-HIV- men. However, the disaggregated functional relationship between ACTH and cortisol in METH + HIV+ MSM was independent of these factors. Further research is needed to characterize the bio-behavioral pathways that explain dysregulated HPA axis functioning in HIV-positive, methamphetamine-using MSM. Copyright © 2017 John Wiley & Sons, Ltd.

  18. What can we know from pituitary-adrenal hormones about the nature and consequences of exposure to emotional stressors?

    Science.gov (United States)

    Armario, Antonio; Daviu, Núria; Muñoz-Abellán, Cristina; Rabasa, Cristina; Fuentes, Silvia; Belda, Xavier; Gagliano, Humberto; Nadal, Roser

    2012-07-01

    Exposure to stress induces profound physiological and behavioral changes in the organisms and some of these changes may be important regarding stress-induced pathologies and animal models of psychiatric diseases. Consequences of stress are dependent on the duration of exposure to stressors (acute, chronic), but also of certain characteristics such as intensity, controllability, and predictability. If some biological variables were able to reflect these characteristics, they could be used to predict negative consequences of stress. Among the myriad of physiological changes caused by stress, only a restricted number of variables appears to reflect the intensity of the situation, mainly plasma levels of ACTH and adrenaline. Peripheral hypothalamic-pituitary-adrenal (HPA) hormones (ACTH and corticosterone) are also able to reflect fear conditioning. In contrast, the activation of the HPA axis is not consistently related to anxiety as evaluated by classical tests such as the elevated plus-maze. Similarly, there is no consistent evidence about the sensitivity of the HPA axis to psychological variables such as controllability and predictability, despite the fact that: (a) lack of control over aversive stimuli can induce behavioral alterations not seen in animals which exert control, and (b) animals showed clear preference for predictable versus unpredictable stressful situations. New studies are needed to re-evaluate the relationship between the HPA axis and psychological stress characteristics using ACTH instead of corticosterone and taking advantages of our current knowledge about the regulation of this important stress system.

  19. Investigation of Oxytocin Secretion in Anorexia Nervosa and Bulimia Nervosa: Relationships to Temperament Personality Dimensions.

    Science.gov (United States)

    Monteleone, Alessio Maria; Scognamiglio, Pasquale; Volpe, Umberto; Di Maso, Virginia; Monteleone, Palmiero

    2016-01-01

    Published studies suggested an implication of oxytocin in some temperament characteristics of personality. Therefore, we measured oxytocin secretion in 23 women with anorexia nervosa (AN), 27 with bulimia nervosa (BN) and 19 healthy controls and explored the relationships between circulating oxytocin and patients' personality traits. Plasma oxytocin levels were significantly reduced in AN women but not in BN ones. In healthy women, the attachment subscale scores of the reward dependence temperament and the harm avoidance (HA) scores explained 82% of the variability in circulating oxytocin. In BN patients, plasma oxytocin resulted to be negatively correlated with HA, whereas no significant correlations emerged in AN patients. These findings confirm a dysregulation of oxytocin production in AN but not in BN and show, for the first time, a disruption of the associations between hormone levels and patients' temperament traits, which may have a role in certain deranged behaviours of eating disorder patients. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

  20. Neurobiology of Maternal Stress: Role of Social Rank and Central Oxytocin in Hypothalamic-Pituitary Adrenal Axis Modulation

    Directory of Open Access Journals (Sweden)

    Jeremy D Coplan

    2015-07-01

    Full Text Available Background: Chronic stress may conceivably require plasticity of maternal physiology and behavior to cope with the conflicting primary demands of infant rearing and foraging for food. In addition, social rank may play a pivotal role in mandating divergent homeostatic adaptations in cohesive social groups. We examined cerebrospinal fluid (CSF oxytocin (OT levels and hypothalamic pituitary adrenal (HPA axis regulation in the context of maternal social stress and assessed the contribution of social rank to dyadic-distance as reflective of distraction from normative maternal-infant interaction. Methods: Twelve socially-housed mother-infant bonnet macaque dyads were studied after variable foraging demand (VFD exposure compared to 11 unstressed dyads. Dyadic-distance was determined by behavioral observation. Social ranking was performed blindly by two observers. Post-VFD maternal plasma cortisol and CSF OT were compared to corresponding measures in non-VFD exposed mothers. Results: High social rank was associated with increased dyadic-distance only in VFD-exposed dyads and not in control dyads. In mothers unexposed to VFD, social rank was not related to maternal cortisol levels whereas VFD-exposed dominant versus subordinate mothers exhibited increased plasma cortisol. Maternal CSF OT directly predicted maternal cortisol only in VFD-exposed mothers. CSF OT was higher in dominant versus subordinate mothers. VFD-exposed mothers with high cortisol specifically exhibited CSF OT elevations in comparison to control groups. Conclusions: Pairing of maternal social rank to dyadic-distance in VFD presumably reduces maternal contingent responsivity, with ensuing long-term sequelae. VFD-exposure dichotomizes maternal HPA axis response as a function of social rank with relatively reduced cortisol in subordinates. OT may serve as a homeostatic buffer during maternal stress exposure.

  1. The role of oxytocin in the pathogenesis and treatment of schizophrenia

    Directory of Open Access Journals (Sweden)

    Jusiak Katarzyna

    2017-12-01

    Full Text Available Introduction: Until recently, oxytocin was mainly associated with the pathophysiology of childbirth and sexual functions, but lately this hormone has become the object of interest to psychiatry and psychology due to the significant influence of oxytocin on human behavior in the field of social and emotional functioning. Current scientific research focuses on the participation of oxytocin in the pathogenesis and therapy of mental disorders.

  2. Lithium ameliorates sleep deprivation-induced mania-like behavior, hypothalamic-pituitary-adrenal (HPA) axis alterations, oxidative stress and elevations of cytokine concentrations in the brain and serum of mice.

    Science.gov (United States)

    Valvassori, Samira S; Resende, Wilson R; Dal-Pont, Gustavo; Sangaletti-Pereira, Heron; Gava, Fernanda F; Peterle, Bruna R; Carvalho, André F; Varela, Roger B; Dal-Pizzol, Felipe; Quevedo, João

    2017-06-01

    The goal of the present study was to investigate the effects of lithium administration on behavior, oxidative stress parameters and cytokine levels in the periphery and brain of mice subjected to an animal model of mania induced by paradoxical sleep deprivation (PSD). Male C57 mice were treated with saline or lithium for 7 days. The sleep deprivation protocol started on the 5th day during for the last 36 hours of the treatment period. Immediately after the sleep deprivation protocol, animals locomotor activity was evaluated and serum and brain samples was extracted to evaluation of corticosterone and adrenocorticotropic hormone circulating levels, oxidative stress parameters and citokynes levels. The results showed that PSD induced hyperactivity in mice, which is considered a mania-like behavior. PSD increased lipid peroxidation and oxidative damage to DNA, as well as causing alterations to antioxidant enzymes in the frontal cortex, hippocampus and serum of mice. In addition, PSD increased the levels of cytokines in the brains of mice. Treatment with lithium prevented the mania-like behavior, oxidative damage and cytokine alterations induced by PSD. Improving our understanding of oxidative damage in biomolecules, antioxidant mechanisms and the inflammatory system - alterations presented in the animal models of mania - is important in helping us to improve our knowledge concerning the pathophysiology of BD, and the mechanisms of action employed by mood stabilizers. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. "Lie to me"-Oxytocin impairs lie detection between sexes.

    Science.gov (United States)

    Pfundmair, Michaela; Erk, Wiebke; Reinelt, Annika

    2017-10-01

    The hormone oxytocin modulates various aspects of social behaviors and even seems to lead to a tendency for gullibility. The aim of the current study was to investigate the effect of oxytocin on lie detection. We hypothesized that people under oxytocin would be particularly susceptible to lies told by people of the opposite sex. After administration of oxytocin or a placebo, male and female participants were asked to judge the veracity of statements from same- vs. other-sex actors who either lied or told the truth. Results showed that oxytocin decreased the ability of both male and female participants to correctly classify other-sex statements as truths or lies compared to placebo. This effect was based on a lower ability to detect lies and not a stronger bias to regard truth statements as false. Revealing a new effect of oxytocin, the findings may support assumptions about the hormone working as a catalyst for social adaption. Copyright © 2017. Published by Elsevier Ltd.

  4. Promoting social behavior with oxytocin in high-functioning autism spectrum disorders.

    Science.gov (United States)

    Andari, Elissar; Duhamel, Jean-René; Zalla, Tiziana; Herbrecht, Evelyn; Leboyer, Marion; Sirigu, Angela

    2010-03-02

    Social adaptation requires specific cognitive and emotional competences. Individuals with high-functioning autism or with Asperger syndrome cannot understand or engage in social situations despite preserved intellectual abilities. Recently, it has been suggested that oxytocin, a hormone known to promote mother-infant bonds, may be implicated in the social deficit of autism. We investigated the behavioral effects of oxytocin in 13 subjects with autism. In a simulated ball game where participants interacted with fictitious partners, we found that after oxytocin inhalation, patients exhibited stronger interactions with the most socially cooperative partner and reported enhanced feelings of trust and preference. Also, during free viewing of pictures of faces, oxytocin selectively increased patients' gazing time on the socially informative region of the face, namely the eyes. Thus, under oxytocin, patients respond more strongly to others and exhibit more appropriate social behavior and affect, suggesting a therapeutic potential of oxytocin through its action on a core dimension of autism.

  5. THE EFFECTIVENESS OF COMBINATION OF OXYTOCIN AND ENDORPHIN MASSAGE ON UTERINE INVOLUTION IN PRIMIPAROUS MOTHERS

    Directory of Open Access Journals (Sweden)

    Nurmala Sari

    2017-10-01

    Full Text Available Background: One of the puerperal complication is uterine subinvolution that can cause bleeding to maternal death. Oxytocin massage can stimulate oxytocin hormone that plays a role in the process of uterine involution. Endorphine massage can increase the release of oxytocin and endorphine hormone that give a sense of calm and comfort. It also increases production of oxytocin hormone that can improve the process of uterine involution. Objective: To prove the effectiveness of a combination of oxytocin massage and endorphine massage to uterine involution in primiparaous mothers during postpartum period. Methods: This was a quasy-experimental study with pretest-posttest with control group design. Total samples were 44 normal postpartum mothers selected using purposive sampling technique, which were randomly assigned in four groups, namely: 1 oxytocin massage group, 2 endorphin massage group, 3 combined oxytocin-endorphin massage group, and 4 control group. The data were analyzed using univariate, bivariate and One Way Anova to test the effectiveness of the intervention. Results: There were statistically significant differences of fundal height before and after intervention among the four groups (p=<0.05. Conclusion: The combination of oxytocin massage and endorphine massage proved most effective in accelerating uterine involution in normal postpartum mothers.

  6. Hypothalamic oxytocin mediates social buffering of the stress response.

    Science.gov (United States)

    Smith, Adam S; Wang, Zuoxin

    2014-08-15

    While stressful life events can enhance the risk of mental disorders, positive social interactions can propagate good mental health and normal behavioral routines. Still, the neural systems that promote these benefits are undetermined. Oxytocin is a hormone involved in social behavior and stress; thus, we focus on the impact that social buffering has on the stress response and the governing effects of oxytocin. Female prairie voles (Microtus ochrogaster) were exposed to 1 hour immobilization stress and then recovered alone or with their male partner to characterize the effect of social contact on the behavioral, physiological, and neuroendocrine stress response. In addition, we treated immobilized female voles recovering alone with oxytocin or vehicle and female voles recovering with their male partner with a selective oxytocin receptor antagonist or vehicle. Group sizes varied from 6 to 8 voles (N = 98 total). We found that 1 hour immobilization increased anxiety-like behaviors and circulating levels of corticosterone, a stress hormone, in female prairie voles recovering alone but not the female prairie voles recovering with their male partner. This social buffering by the male partner on biobehavioral responses to stress was accompanied by increased oxytocin release in the paraventricular nucleus of the hypothalamus. Intra-paraventricular nucleus oxytocin injections reduced behavioral and corticosterone responses to immobilization, whereas injections of an oxytocin receptor antagonist blocked the effects of the social buffering. Together, our data demonstrate that paraventricular nucleus oxytocin mediates the social buffering effects on the stress response and thus may be a target for treatment of stress-related disorders. Published by Society of Biological Psychiatry on behalf of Society of Biological Psychiatry.

  7. Oxytocin in survivors of childhood-onset craniopharyngioma.

    Science.gov (United States)

    Daubenbüchel, Anna M M; Hoffmann, Anika; Eveslage, Maria; Özyurt, Jale; Lohle, Kristin; Reichel, Julia; Thiel, Christiane M; Martens, Henri; Geenen, Vincent; Müller, Hermann L

    2016-11-01

    Quality of survival of childhood-onset craniopharyngioma patients is frequently impaired by hypothalamic involvement or surgical lesions sequelae such as obesity and neuropsychological deficits. Oxytocin, a peptide hormone produced in the hypothalamus and secreted by posterior pituitary gland, plays a major role in regulation of behavior and body composition. In a cross-sectional study, oxytocin saliva concentrations were analyzed in 34 long-term craniopharyngioma survivors with and without hypothalamic involvement or treatment-related damage, recruited in the German Childhood Craniopharyngioma Registry, and in 73 healthy controls, attending the Craniopharyngioma Support Group Meeting 2014. Oxytocin was measured in saliva of craniopharyngioma patients and controls before and after standardized breakfast and associations with gender, body mass index, hypothalamic involvement, diabetes insipidus, and irradiation were analyzed. Patients with preoperative hypothalamic involvement showed similar oxytocin levels compared to patients without hypothalamic involvement and controls. However, patients with surgical hypothalamic lesions grade 1 (anterior hypothalamic area) presented with lower levels (p = 0.017) of oxytocin under fasting condition compared to patients with surgical lesion of posterior hypothalamic areas (grade 2) and patients without hypothalamic lesions (grade 0). Craniopharyngioma patients' changes in oxytocin levels before and after breakfast correlated (p = 0.02) with their body mass index. Craniopharyngioma patients continue to secrete oxytocin, especially when anterior hypothalamic areas are not involved or damaged, but oxytocin shows less variation due to nutrition. Oxytocin supplementation should be explored as a therapeutic option in craniopharyngioma patients with hypothalamic obesity and/or behavioral pathologies due to lesions of specific anterior hypothalamic areas. Clinical trial number: KRANIOPHARYNGEOM 2000/2007(NCT00258453; NCT01272622).

  8. Variation in Oxytocin is Related to Variation in Affiliative Behavior in Monogamous, Pairbonded Tamarins

    OpenAIRE

    Snowdon, Charles T.; Pieper, Bridget A.; Boe, Carla Y.; Cronin, Katherine A.; Kurian, Aimee V.; Ziegler, Toni E.

    2010-01-01

    Oxytocin plays an important role in monogamous pairbonded female voles, but not in polygamous voles. Here we examined a socially-monogamous cooperatively breeding primate where both sexes share in parental care and territory defense for within species variation in behavior and female and male oxytocin levels in 14 pairs of cotton-top tamarins (Saguinus oedipus), In order to obtain a stable chronic assessment of hormones and behavior, we observed behavior and collected urinary hormonal samples...

  9. Oxytocin and first impressions

    OpenAIRE

    Friberg, Mads

    2012-01-01

    Subtle facial expressions may cause "core impressions" of other people, i.e. a feeling of like or dislike witch is affected by facial cues that is not explicitly and consciously recognized. In the present investigation, we were interested in how the neuropeptide oxytocin affects recognition of these subtle facial expressions. Participants received oxytocin or placebo, and viewed static and dynamic "hybrid" faces that showed a facial expression (happiness, anger, fear, sadness) only in the lo...

  10. Radioimmunoassay of oxytocin

    International Nuclear Information System (INIS)

    Dawood, M.Y.; Raghavan, K.S.; Pociask, C.

    1978-01-01

    The evaluation of a radioimmunoassay of oxytocin is described. The method involved careful collection and transportation of blood at 4 0 C, acidification of the plasma, extraction with Fuller's earth and radioimmunoassay using antisera raised in rabbits immunized against oxytocin conjugated to bovine serum albumin and 125 I-labelled oxytocin. The antisera showed insignificant cross-reaction with a variety of small peptides including vasopressin and vasotocin. The limit of detection of the assay was 2.5 pg with intra-assay and interassay coefficients of variation of 7 to 15% and 12 to 18% respectively. Seventy-seven per cent (88 out of 116) of the pregnant women tested had detect-able maternal plasma oxytocin. Serial samples of maternal plasma showed a significant increase in oxytocin from the first to the second stage of labour and a significant decrease in the third stage. Oxytocin concentrations in the umbilical arterial plasma were significantly higher in patients in labour. The significance of these findings is discussed. (author)

  11. Oxytocin as an Indicator of Psychological and Social Well-Being in Domesticated Animals: A Critical Review

    Directory of Open Access Journals (Sweden)

    Jean-Loup Rault

    2017-09-01

    Full Text Available Oxytocin is often portrayed as a hormone specific to social behavior, reflective of positive welfare states, and linked to mental states. Research on oxytocin in domesticated animal species has been few to date but is rapidly increasing (in dog, pig, cattle, sheep, with direct implications for animal welfare. This review evaluates the evidence for the specificity of oxytocin as an indicator of: 1. Social, 2. Positive, and 3. Psychological well-being. Oxytocin has most often been studied in socially relevant paradigms, with a lack of non-social control paradigms. Oxytocin research appears biased toward investigating positive valence, with a lack of control in valence or arousal. Oxytocin actions are modulated by the environmental and social contexts, which are important factors to consider. Limited evidence supports that oxytocin's actions are linked to psychological states; nevertheless whether this is a direct effect of oxytocin per se remains to be demonstrated. Overall, it is premature to judge oxytocin's potential as an animal welfare indicator given the few and discrepant findings and a lack of standardization in methodology. We cover potential causes for discrepancies and suggest solutions through appropriate methodological design, oxytocin sampling or delivery, analysis and reporting. Of particular interest, the oxytocinergic system as a whole remains poorly understood. Appreciation for the differences that social contact and group living pose in domesticated species and the way they interact with humans should be key considerations in using oxytocin as a psychosocial indicator of well-being.

  12. Mechanisms of the anti-obesity effects of oxytocin in diet-induced obese rats.

    Directory of Open Access Journals (Sweden)

    Nicolas Deblon

    Full Text Available Apart from its role during labor and lactation, oxytocin is involved in several other functions. Interestingly, oxytocin- and oxytocin receptor-deficient mice develop late-onset obesity with normal food intake, suggesting that the hormone might exert a series of beneficial metabolic effects. This was recently confirmed by data showing that central oxytocin infusion causes weight loss in diet-induced obese mice. The aim of the present study was to unravel the mechanisms underlying such beneficial effects of oxytocin. Chronic central oxytocin infusion was carried out in high fat diet-induced obese rats. Its impact on body weight, lipid metabolism and insulin sensitivity was determined. We observed a dose-dependent decrease in body weight gain, increased adipose tissue lipolysis and fatty acid β-oxidation, as well as reduced glucose intolerance and insulin resistance. The additional observation that plasma oxytocin levels increased upon central infusion suggested that the hormone might affect adipose tissue metabolism by direct action. This was demonstrated using in vitro, ex vivo, as well as in vivo experiments. With regard to its mechanism of action in adipose tissue, oxytocin increased the expression of stearoyl-coenzyme A desaturase 1, as well as the tissue content of the phospholipid precursor, N-oleoyl-phosphatidylethanolamine, the biosynthetic precursor of the oleic acid-derived PPAR-alpha activator, oleoylethanolamide. Because PPAR-alpha regulates fatty acid β-oxidation, we hypothesized that this transcription factor might mediate the oxytocin effects. This was substantiated by the observation that, in contrast to its effects in wild-type mice, oxytocin infusion failed to induce weight loss and fat oxidation in PPAR-alpha-deficient animals. Altogether, these results suggest that oxytocin administration could represent a promising therapeutic approach for the treatment of human obesity and type 2 diabetes.

  13. Oxytocin, testosterone, and human social cognition.

    Science.gov (United States)

    Crespi, Bernard J

    2016-05-01

    I describe an integrative social-evolutionary model for the adaptive significance of the human oxytocinergic system. The model is based on a role for this hormone in the generation and maintenance of social familiarity and affiliation across five homologous, functionally similar, and sequentially co-opted contexts: mothers with offspring, female and male mates, kin groups, individuals with reciprocity partners, and individuals within cooperating and competing social groups defined by culture. In each situation, oxytocin motivates, mediates and rewards the cognitive and behavioural processes that underlie the formation and dynamics of a more or less stable social group, and promotes a relationship between two or more individuals. Such relationships may be positive (eliciting neurological reward, reducing anxiety and thus indicating fitness-enhancing effects), or negative (increasing anxiety and distress, and thus motivating attempts to alleviate a problematic, fitness-reducing social situation). I also present evidence that testosterone exhibits opposite effects from oxytocin on diverse aspects of cognition and behaviour, most generally by favouring self-oriented, asocial and antisocial behaviours. I apply this model for effects of oxytocin and testosterone to understanding human psychological disorders centrally involving social behaviour. Reduced oxytocin and higher testosterone levels have been associated with under-developed social cognition, especially in autism. By contrast, some combination of oxytocin increased above normal levels, and lower testosterone, has been reported in a notable number of studies of schizophrenia, bipolar disorder and depression, and, in some cases, higher oxytocin involves maladaptively 'hyper-developed' social cognition in these conditions. This pattern of findings suggests that human social cognition and behaviour are structured, in part, by joint and opposing effects of oxytocin and testosterone, and that extremes of such joint

  14. First experiences with neuropsychological effects of oxytocin administration in childhood-onset craniopharyngioma.

    Science.gov (United States)

    Hoffmann, Anika; Özyurt, Jale; Lohle, Kristin; Reichel, Julia; Thiel, Christiane M; Müller, Hermann L

    2017-04-01

    The hypothalamic hormone oxytocin plays a major role in regulation of behavior and body composition. Quality of survival is frequently impaired in childhood craniopharyngioma patients due to sequelae such as behavioral deficits and severe obesity caused by tumor or treatment-related hypothalamic lesions. In our pilot cross-sectional study, we analyzed emotion recognition abilities and oxytocin concentrations in saliva and urine before and after single nasal administration of 24 IU oxytocin in 10 craniopharyngioma patients. Four craniopharyngioma presented with grade I lesions (limited to anterior hypothalamic areas) and 6 craniopharyngioma with grade II lesions (involving mammillary bodies and posterior hypothalamic areas). Emotional tasks were assessed before and after administration of oxytocin using the Geneva multimodal emotion portrayals corpus and the Multidimensional Mood Questionnaire. All patients presented with detectable levels of oxytocin before administration. Nasal administration of oxytocin was well-tolerated and resulted in increased oxytocin concentrations in saliva and urine. After oxytocin administration, craniopharyngioma patients with postsurgical lesions limited to the anterior hypothalamus area showed improvements in emotional identifications compared to craniopharyngioma patients with lesions of anterior and posterior hypothalamic areas. Focusing on correct assignments to positive and negative emotion categories, craniopharyngioma patients improved assignment to negative emotions. Oxytocin might have positive effects on emotion perception in craniopharyngioma patients with specific lesions of the anterior hypothalamic area. Further studies on larger cohorts are warranted.

  15. Hormones and social preferences

    NARCIS (Netherlands)

    Buser, T.

    2011-01-01

    We examine whether social preferences are determined by hormones. We do this by investigating whether markers for the strength of prenatal testosterone exposure (finger length ratios) and current exposure to progesterone and oxytocin (the menstrual cycle) are correlated with choices in social

  16. Epigenetic modification of the oxytocin and glucocorticoid receptor genes is linked to attachment avoidance in young adults.

    Science.gov (United States)

    Ein-Dor, Tsachi; Verbeke, Willem J M I; Mokry, Michal; Vrtička, Pascal

    2018-08-01

    Attachment in the context of intimate pair bonds is most frequently studied in terms of the universal strategy to draw near, or away, from significant others at moments of personal distress. However, important interindividual differences in the quality of attachment exist, usually captured through secure versus insecure - anxious and/or avoidant - attachment orientations. Since Bowlby's pioneering writings on the theory of attachment, it has been assumed that attachment orientations are influenced by both genetic and social factors - what we would today describe and measure as gene by environment interaction mediated by epigenetic DNA modification - but research in humans on this topic remains extremely limited. We for the first time examined relations between intra-individual differences in attachment and epigenetic modification of the oxytocin receptor (OXTR) and glucocorticoid receptor (NR3C1) gene promoter in 109 young adult human participants. Our results revealed that attachment avoidance was significantly and specifically associated with increased OXTR and NR3C1 promoter methylation. These findings offer first tentative clues on the possible etiology of attachment avoidance in humans by showing epigenetic modification in genes related to both social stress regulation and HPA axis functioning.

  17. Effects of 2G on Gene Expression of Stress-Related Hormones in Rat Placenta

    Science.gov (United States)

    Benson, S.; Talyansky, Y.; Moyer, E. L.; Lowe, M.; Baer, L. A.; Ronca, A. E.

    2017-01-01

    Understanding the effects of spaceflight on mammalian reproductive and developmental physiology is important to future human space exploration and permanent settlement beyond Earth orbit. Fetal developmental programming, including modulation of the HPA axis, is thought to originate at the placental-uterine interface, where both transfer of maternal hormones to the fetus and synthesis of endogenous hormones occurs. In healthy rats, fetal corticosterone levels are kept significantly lower by 11BetaHSD-2, which inactivates corticosterone by conversion into cortisone. Placental tissues express endogenous HPA axis-associated hormones including corticotropin-releasing hormone (CRH), pre-opiomelanocortin (POMC), and vasopressin, which may contribute to fetal programming alongside maternal hormones. DNA methylase 3A, 11BetaHSD-2, and 11BetaHSD-1, which are involved in the regulation of maternal cortisol transfer and modulation of the HPA axis, are also expressed in placental tissues along with glucocorticoid receptor and may be affected by differential gravity exposure during pregnancy. Fetuses may respond differently to maternal glucocorticoid exposure during gestation through sexually dimorphic expression of corticosterone-modulating hormones. To elucidate effects of altered gravity on placental gene expression, here we present a ground-based analogue study involving continuous centrifugation to produce 2g hypergravity. We hypothesized that exposure to 2g would induce a decrease in 11BetaHSD-2 expression through the downregulation of DNA methylase 3a and GC receptor, along with concurrent upregulation in endogenous CRH, POMC, and vasopressin expression. Timed pregnant female rats were exposed to 2G from Gestational day 6 to Gestational day 20, and comparisons made with Stationary Control (SC) and Vivarium Control (VC) dams at 1G. Dams were euthanized and placentas harvested on G20. We homogenized placental tissues, extracted and purified RNA, synthesized cDNA, and

  18. DNA methylation of specific CpG sites in the promoter region regulates the transcription of the mouse oxytocin receptor.

    Directory of Open Access Journals (Sweden)

    Shimrat Mamrut

    Full Text Available Oxytocin is a peptide hormone, well known for its role in labor and suckling, and most recently for its involvement in mammalian social behavior. All central and peripheral actions of oxytocin are mediated through the oxytocin receptor, which is the product of a single gene. Transcription of the oxytocin receptor is subject to regulation by gonadal steroid hormones, and is profoundly elevated in the uterus and mammary glands during parturition. DNA methylation is a major epigenetic mechanism that regulates gene transcription, and has been linked to reduced expression of the oxytocin receptor in individuals with autism. Here, we hypothesized that transcription of the mouse oxytocin receptor is regulated by DNA methylation of specific sites in its promoter, in a tissue-specific manner. Hypothalamus-derived GT1-7, and mammary-derived 4T1 murine cell lines displayed negative correlations between oxytocin receptor transcription and methylation of the gene promoter, and demethylation caused a significant enhancement of oxytocin receptor transcription in 4T1 cells. Using a reporter gene assay, we showed that methylation of specific sites in the gene promoter, including an estrogen response element, significantly inhibits transcription. Furthermore, methylation of the oxytocin receptor promoter was found to be differentially correlated with oxytocin receptor expression in mammary glands and the uterus of virgin and post-partum mice, suggesting that it plays a distinct role in oxytocin receptor transcription among tissues and under different physiological conditions. Together, these results support the hypothesis that the expression of the mouse oxytocin receptor gene is epigenetically regulated by DNA methylation of its promoter.

  19. Oxytocin increases the influence of public service advertisements.

    Directory of Open Access Journals (Sweden)

    Pei-Ying Lin

    Full Text Available This paper presents a neurophysiologic model of effective public service advertisements (PSAs and reports two experiments that test the model. In Experiment 1, we show that after watching 16 PSAs participants who received oxytocin, compared to those given a placebo, donated to 57% more causes, donated 56% more money, and reported 17% greater concern for those in the ads. In Experiment 2, we measured adrenocorticotropin hormone (ACTH and oxytocin levels in blood before and after participants watched a PSA. As predicted by the model, donations occurred when participants had increases in both ACTH and oxytocin. Our results indicate that PSAs with social content that cause OT release will be more effective than those that do not. Our results also explain why some individuals do not respond to PSAs.

  20. Oxytocin increases the influence of public service advertisements.

    Science.gov (United States)

    Lin, Pei-Ying; Grewal, Naomi Sparks; Morin, Christophe; Johnson, Walter D; Zak, Paul J

    2013-01-01

    This paper presents a neurophysiologic model of effective public service advertisements (PSAs) and reports two experiments that test the model. In Experiment 1, we show that after watching 16 PSAs participants who received oxytocin, compared to those given a placebo, donated to 57% more causes, donated 56% more money, and reported 17% greater concern for those in the ads. In Experiment 2, we measured adrenocorticotropin hormone (ACTH) and oxytocin levels in blood before and after participants watched a PSA. As predicted by the model, donations occurred when participants had increases in both ACTH and oxytocin. Our results indicate that PSAs with social content that cause OT release will be more effective than those that do not. Our results also explain why some individuals do not respond to PSAs.

  1. Induction of oviposition by the administration of oxytocin in hawksbill turtles.

    Science.gov (United States)

    Kawazu, Isao; Kino, Masakatsu; Maeda, Konomi; Yamaguchi, Yasuhiro; Sawamukai, Yutaka

    2014-12-01

    We set out to develop an oviposition induction technique for captive female hawksbill turtles Eretmochelys imbricata. The infertile eggs of nine females were induced to develop by the administration of follicle-stimulating hormone, after which we investigated the effects of administering oxytocin on oviposition. Seven of the turtles were held in a stationary horizontal position on a retention stand, and then oxytocin was administrated (0.6-0.8 units/kg of body weight; 5 mL). The seven turtles were retained for a mandatory 2 h period after oxytocin administration, and were then returned to the holding tanks. As the control, normal saline (5 mL) was administered to the other two turtles, followed by the administration of oxytocin after 24 h. The eggs in oviducts of all nine turtles were observed by ultrasonography at 24 h after oxytocin administration. The control experiment validated that stationary retention and normal saline administration had no effect on egg oviposition. Eight of the turtles began ovipositing eggs at 17-43 min after oxytocin administration, while one began ovipositing in the holding tank immediately after retention. All turtles finished ovipositing eggs within 24 h of oxytocin administration. This report is the first to demonstrate successful induced oviposition in sea turtles. We suggest that the muscles in the oviducts of hawksbill turtles may respond to relatively lower doses of oxytocin (inducing contractions) compared to land and freshwater turtles (4-40 units/kg) based on existing studies.

  2. A randomised controlled trial comparing oxytocin and oxytocin + ...

    African Journals Online (AJOL)

    'rule of threes' as a means of administering oxytocin: 3 IU IVI as a slow bolus every 3 minutes depending on the contraction of the uterus.[5] The following guidelines were published in the SAMJ in. April 2015 for primary prophylaxis of PPH at CS:[6] (i) oxytocin. 2.5 IU IVI as a slow bolus (over 30 seconds); (ii) oxytocin 7.5 IU.

  3. Promoting social behavior with oxytocin in high-functioning autism spectrum disorders

    OpenAIRE

    Andari, Elissar; Duhamel, Jean-René; Zalla, Tiziana; Herbrecht, Evelyn; Leboyer, Marion; Sirigu, Angela

    2010-01-01

    Social adaptation requires specific cognitive and emotional competences. Individuals with high-functioning autism or with Asperger syndrome cannot understand or engage in social situations despite preserved intellectual abilities. Recently, it has been suggested that oxytocin, a hormone known to promote mother-infant bonds, may be implicated in the social deficit of autism. We investigated the behavioral effects of oxytocin in 13 subjects with autism. In a simulated ball game where participan...

  4. Stress, glucocorticoid hormones, and hippocampal neural progenitor cells: implications to mood disorders.

    Science.gov (United States)

    Kino, Tomoshige

    2015-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis and its end-effectors glucocorticoid hormones play central roles in the adaptive response to numerous stressors that can be either internal or external. Thus, this system has a strong impact on the brain hippocampus and its major functions, such as cognition, memory as well as behavior, and mood. The hippocampal area of the adult brain contains neural stem cells or more committed neural progenitor cells, which retain throughout the human life the ability of self-renewal and to differentiate into multiple neural cell lineages, such as neurons, astrocytes, and oligodendrocytes. Importantly, these characteristic cells contribute significantly to the above-indicated functions of the hippocampus, while various stressors and glucocorticoids influence proliferation, differentiation, and fate of these cells. This review offers an overview of the current understanding on the interactions between the HPA axis/glucocorticoid stress-responsive system and hippocampal neural progenitor cells by focusing on the actions of glucocorticoids. Also addressed is a further discussion on the implications of such interactions to the pathophysiology of mood disorders.

  5. Visualization of oxytocin release that mediates paired pulse facilitation in hypothalamic pathways to brainstem autonomic neurons.

    Directory of Open Access Journals (Sweden)

    Ramón A Piñol

    Full Text Available Recent work has shown that oxytocin is involved in more than lactation and uterine contraction. The paraventricular nucleus of the hypothalamus (PVN contains neuroendocrine neurons that control the release of hormones, including vasopressin and oxytocin. Other populations of PVN neurons do not release hormones, but rather project to and release neurotransmitters onto other neurons in the CNS involved in fluid retention, thermoregulation, sexual behavior and responses to stress. Activation of oxytocin receptors can be cardioprotective and reduces the adverse cardiovascular consequences of anxiety and stress, yet how oxytocin can affect heart rate and cardiac function is unknown. While anatomical work has shown the presence of peptides, including oxytocin, in the projections from the PVN to parasympathetic nuclei, electrophysiological studies to date have only demonstrated release of glutamate and activation of fast ligand gated receptors in these pathways. In this study, using rats, we directly show, using sniffer CHO cells that express oxytocin receptors and the Ca2+ indicator R-GECO, that optogenetic activation of channelrhodopsin-2 (ChR2 expressing PVN fibers in the brainstem activates oxytocin receptors in the dorsomotor nucleus of the vagus (DMNV. We also demonstrate that while a single photoactivation of PVN terminals only activates glutamatergic receptors in brainstem cardiac vagal neurons (CVNs, neurons that dominate the neural control of heart rate, both the paired pulse facilitation, and sustained enhancement of glutamate release in this pathway is mediated by activation of oxytocin receptors. Our results provide direct evidence that a pathway from the PVN likely releases oxytocin and enhances short-term plasticity of this critical autonomic connection.

  6. Visualization of Oxytocin Release that Mediates Paired Pulse Facilitation in Hypothalamic Pathways to Brainstem Autonomic Neurons

    Science.gov (United States)

    Piñol, Ramón A.; Jameson, Heather; Popratiloff, Anastas; Lee, Norman H.; Mendelowitz, David

    2014-01-01

    Recent work has shown that oxytocin is involved in more than lactation and uterine contraction. The paraventricular nucleus of the hypothalamus (PVN) contains neuroendocrine neurons that control the release of hormones, including vasopressin and oxytocin. Other populations of PVN neurons do not release hormones, but rather project to and release neurotransmitters onto other neurons in the CNS involved in fluid retention, thermoregulation, sexual behavior and responses to stress. Activation of oxytocin receptors can be cardioprotective and reduces the adverse cardiovascular consequences of anxiety and stress, yet how oxytocin can affect heart rate and cardiac function is unknown. While anatomical work has shown the presence of peptides, including oxytocin, in the projections from the PVN to parasympathetic nuclei, electrophysiological studies to date have only demonstrated release of glutamate and activation of fast ligand gated receptors in these pathways. In this study, using rats, we directly show, using sniffer CHO cells that express oxytocin receptors and the Ca2+ indicator R-GECO, that optogenetic activation of channelrhodopsin-2 (ChR2) expressing PVN fibers in the brainstem activates oxytocin receptors in the dorsomotor nucleus of the vagus (DMNV). We also demonstrate that while a single photoactivation of PVN terminals only activates glutamatergic receptors in brainstem cardiac vagal neurons (CVNs), neurons that dominate the neural control of heart rate, both the paired pulse facilitation, and sustained enhancement of glutamate release in this pathway is mediated by activation of oxytocin receptors. Our results provide direct evidence that a pathway from the PVN likely releases oxytocin and enhances short-term plasticity of this critical autonomic connection. PMID:25379676

  7. Peripheral administration of oxytocin increases social affiliation in the naked mole-rat (Heterocephalus glaber).

    Science.gov (United States)

    Mooney, Skyler J; Douglas, Natasha R; Holmes, Melissa M

    2014-04-01

    The neuropeptide oxytocin regulates a wide variety of social behaviors across diverse species. However, the types of behaviors that are influenced by this hormone are constrained by the species in question and the social organization that a particular species exhibits. Therefore, the present experiments investigated behaviors regulated by oxytocin in a eusocial mammalian species by using the naked mole-rat (Heterocephalus glaber). In Experiment 1, adult non-breeding mole-rats were given intraperitoneal injections of either oxytocin (1mg/kg or 10mg/kg) or saline on alternate days. Animals were then returned to their colony and behavior was recorded for minutes 15-30 post-injection. Both doses of oxytocin increased huddling behavior during this time period. In Experiment 2, animals received intraperitoneal injections of either oxytocin (1mg/kg), an oxytocin-receptor antagonist (0.1mg/kg), a cocktail of oxytocin and the antagonist, or saline across 4 testing days in a counterbalanced design. Animals were placed in either a 2-chamber arena with a familiar conspecific or in a small chamber with 1week old pups from their home colony and behaviors were recorded for minutes 15-30 post-injection. Oxytocin increased investigation of, and time spent in close proximity to, a familiar conspecific; these effects were blocked by the oxytocin antagonist. No effects were seen on pup-directed behavior. These data suggest that oxytocin is capable of modulating affiliative-like behavior in this eusocial species. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Stress-induced cognitive dysfunction: hormone-neurotransmitter interactions in the prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Rebecca M Shansky

    2013-04-01

    Full Text Available The mechanisms and neural circuits that drive emotion and cognition are inextricably linked. Activation of the hypothalamic-pituitary-adrenal (HPA axis as a result of stress or other causes of arousal initiates a flood of hormone and neurotransmitter release throughout the brain, affecting the way we think, decide, and behave. This review will focus on factors that influence the function of the prefrontal cortex (PFC, a brain region that governs higher-level cognitive processes and executive function. The PFC becomes markedly impaired by stress, producing measurable deficits in working memory. These deficits arise from the interaction of multiple neuromodulators, including glucocorticoids, catecholamines, and gonadal hormones; here we will discuss the non- human primate and rodent literature that has furthered our understanding of the circuitry, receptors, and signaling cascades responsible for stress-induced prefrontal dysfunction.

  9. Oxytocin and social functioning

    OpenAIRE

    Jones, Candace; Barrera, Ingrid; Brothers, Shaun; Ring, Robert; Wahlestedt, Claes

    2017-01-01

    Social anxiety is a form of anxiety characterized by continuous fear of one or more social or performance situations. Although multiple treatment modalities (cognitive behavioral therapy, selective serotonin reuptake inhibitors/selective norepinephrine reuptake inhibitors, benzodiazepines) exist for social anxiety, they are effective for only 60% to 70% of patients. Thus, researchers have looked for other candidates for social anxiety treatment. Our review focuses on the peptide oxytocin as a...

  10. Saliva oxytocin measures do not reflect peripheral plasma concentrations after intranasal oxytocin administration in men.

    Science.gov (United States)

    Quintana, Daniel S; Westlye, Lars T; Smerud, Knut T; Mahmoud, Ramy A; Andreassen, Ole A; Djupesland, Per G

    2018-05-16

    Oxytocin plays an important role in social behavior. Thus, there has been significant research interest for the role of the oxytocin system in several psychiatric disorders, and the potential of intranasal oxytocin administration to treat social dysfunction. Measurement of oxytocin concentrations in saliva are sometimes used to approximate peripheral levels of oxytocin; however, the validity of this approach is unclear. In this study, saliva and plasma oxytocin was assessed after two doses of Exhalation Delivery System delivered intranasal oxytocin (8 IU and 24 IU), intravenous oxytocin (1 IU) and placebo in a double-dummy, within-subjects design with men. We found that intranasal oxytocin (8 IU and 24 IU) administration increased saliva oxytocin concentrations in comparison to saliva oxytocin concentration levels after intravenous and placebo administration. Additionally, we found that saliva oxytocin concentrations were not significantly associated with plasma oxytocin concentrations after either intranasal or intravenous oxytocin administration. Altogether, we suggest that saliva oxytocin concentrations do not accurately index peripheral oxytocin after intranasal or intravenous oxytocin administration, at least in men. The data indicates that elevated oxytocin saliva levels after nasal delivery primarily reflect exogenous administered oxytocin that is cleared from the nasal cavity to the oropharynx, and is therefore a weak surrogate for peripheral blood measurements. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Oxytocin Effect on Collective Decision Making: A Randomized Placebo Controlled Study.

    Directory of Open Access Journals (Sweden)

    Uri Hertz

    Full Text Available Collective decision making often benefits both the individuals and the group in a variety of contexts. However, for the group to be successful, individuals should be able to strike a balance between their level of competence and their influence on the collective decisions. The hormone oxytocin has been shown to promote trust, conformism and attention to social cues. We wondered if this hormone may increase participants' (unwarranted reliance on their partners' opinion, resulting in a reduction in collective benefit by disturbing the balance between influence and competence. To test this hypothesis we employed a randomized double-blind placebo-controlled design in which male dyads self-administered intranasal oxytocin or placebo and then performed a visual search task together. Compared to placebo, collective benefit did not decrease under oxytocin. Using an exploratory time dependent analysis, we observed increase in collective benefit over time under oxytocin. Moreover, trial-by-trial analysis showed that under oxytocin the more competent member of each dyad was less likely to change his mind during disagreements, while the less competent member showed a greater willingness to change his mind and conform to the opinion of his more reliable partner. This role-dependent effect may be mediated by enhanced monitoring of own and other's performance level under oxytocin. Such enhanced social learning could improve the balance between influence and competence and lead to efficient and beneficial collaboration.

  12. Oxytocin Effect on Collective Decision Making: A Randomized Placebo Controlled Study.

    Science.gov (United States)

    Hertz, Uri; Kelly, Maria; Rutledge, Robb B; Winston, Joel; Wright, Nicholas; Dolan, Raymond J; Bahrami, Bahador

    2016-01-01

    Collective decision making often benefits both the individuals and the group in a variety of contexts. However, for the group to be successful, individuals should be able to strike a balance between their level of competence and their influence on the collective decisions. The hormone oxytocin has been shown to promote trust, conformism and attention to social cues. We wondered if this hormone may increase participants' (unwarranted) reliance on their partners' opinion, resulting in a reduction in collective benefit by disturbing the balance between influence and competence. To test this hypothesis we employed a randomized double-blind placebo-controlled design in which male dyads self-administered intranasal oxytocin or placebo and then performed a visual search task together. Compared to placebo, collective benefit did not decrease under oxytocin. Using an exploratory time dependent analysis, we observed increase in collective benefit over time under oxytocin. Moreover, trial-by-trial analysis showed that under oxytocin the more competent member of each dyad was less likely to change his mind during disagreements, while the less competent member showed a greater willingness to change his mind and conform to the opinion of his more reliable partner. This role-dependent effect may be mediated by enhanced monitoring of own and other's performance level under oxytocin. Such enhanced social learning could improve the balance between influence and competence and lead to efficient and beneficial collaboration.

  13. Sex-specific associations between peripheral oxytocin and emotion perception in schizophrenia.

    Science.gov (United States)

    Rubin, Leah H; Carter, C Sue; Drogos, Lauren; Jamadar, Rhoda; Pournajafi-Nazarloo, Hossein; Sweeney, John A; Maki, Pauline M

    2011-08-01

    We previously reported that higher levels of peripheral oxytocin are associated with lower levels of positive, general, and overall symptoms in women but not in men with schizophrenia. Here we investigate the influence of sex, sex steroid hormone fluctuations, and peripheral oxytocin levels on emotional processing in men and women with schizophrenia. Twenty-two women with schizophrenia and 31 female controls completed the Penn Emotion Acuity Test (PEAT), a facial emotion recognition and perception task, during two menstrual cycle phases: 1) early follicular (Days 2-4; low estrogen/progesterone) and 2) midluteal (Days 20-22; high estrogen/progesterone). Twenty-six males with schizophrenia and 26 male controls completed testing at comparable intervals. We obtained plasma hormone assays of estrogen, progesterone, testosterone, and oxytocin. No sex differences were noted on the PEAT. Plasma oxytocin levels did not fluctuate across phases of the menstrual cycle. However, female patients and controls more accurately identified facial emotions during the early follicular versus midluteal phase (pmen. Like healthy women, women with schizophrenia demonstrate menstrual-cycle dependent fluctuations in recognizing emotional cues. Like healthy women, female patients with higher levels of oxytocin perceived faces as happier. Future studies need to address whether this sex-specific relationship is associated with trust and other positive emotions, and whether exogenous oxytocin might enhance mood states and social interaction in female or all schizophrenia patients. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans.

    Science.gov (United States)

    Rodrigues, Sarina M; Saslow, Laura R; Garcia, Natalia; John, Oliver P; Keltner, Dacher

    2009-12-15

    Oxytocin, a peptide that functions as both a hormone and neurotransmitter, has broad influences on social and emotional processing throughout the body and the brain. In this study, we tested how a polymorphism (rs53576) of the oxytocin receptor relates to two key social processes related to oxytocin: empathy and stress reactivity. Compared with individuals homozygous for the G allele of rs53576 (GG), individuals with one or two copies of the A allele (AG/AA) exhibited lower behavioral and dispositional empathy, as measured by the "Reading the Mind in the Eyes" Test and an other-oriented empathy scale. Furthermore, AA/AG individuals displayed higher physiological and dispositional stress reactivity than GG individuals, as determined by heart rate response during a startle anticipation task and an affective reactivity scale. Our results provide evidence of how a naturally occurring genetic variation of the oxytocin receptor relates to both empathy and stress profiles.

  15. The role of oxytocin in relationships between dogs and humans and potential applications for the treatment of separation anxiety in dogs.

    Science.gov (United States)

    Thielke, Lauren E; Udell, Monique A R

    2017-02-01

    The hormone oxytocin plays an important role in attachment formation and bonding between humans and domestic dogs. Recent research has led to increased interest in potential applications for intranasal oxytocin to aid with the treatment of psychological disorders in humans. While a few studies have explored the effects of intranasally administered oxytocin on social cognition and social bonding in dogs, alternative applications have not yet been explored for the treatment of behavioural problems in this species. One potentially important application for intranasal oxytocin in dogs could be the treatment of separation anxiety, a common attachment disorder in dogs. Here we provide an overview of what is known about the role of oxytocin in the human-dog bond and canine separation anxiety, and discuss considerations for future research looking to integrate oxytocin into behavioural treatment based on recent findings from both the human and dog literature. © 2015 Cambridge Philosophical Society.

  16. Something to talk about: Gossip increases oxytocin levels in a near real-life situation.

    Science.gov (United States)

    Brondino, Natascia; Fusar-Poli, Laura; Politi, Pierluigi

    2017-03-01

    Gossip is a pervasive social behavior. Its evolutionary survival seems related to its social functions, such as establishing group rules, punishing trespassers, exercising social influence through reputational systems, and developing and strengthening social bonds. We aimed at evaluating the effect of gossip on hormones (oxytocin and cortisol) and at identifying potential mediators of hormonal response to gossip. Twenty-two female students were randomly assigned to a gossip conversation or to an emotional non-gossip conversation. Additionally, all participants underwent a neutral conversation on the second day of the study. Salivary oxytocin and cortisol levels were measured. Oxytocin increased significantly in the gossip compared to the emotional non-gossip conversation. A decrease in cortisol levels was observed in all three conditions (gossip, emotional non-gossip, neutral). Change in cortisol levels was similar across conditions. Psychological characteristics (e.g. empathy, autistic traits, perceived stress, envy) did not affect oxytocin rise in the gossip condition. Our findings suggest that oxytocin may represent a potential hormonal correlate of gossip behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Effects of Oxytocin Administration on Receiving Help.

    Science.gov (United States)

    Human, Lauren J; Woolley, Joshua D; Mendes, Wendy Berry

    2017-11-27

    Receiving help can be a "mixed blessing." Despite the many psychosocial benefits it can carry, it sometimes has negative psychological consequences, such as loss in self-esteem or enhanced guilt. It is, therefore, important to understand the factors that modify responses to receiving help from others. We explored the role of the hormone oxytocin (OT) on affective and social responses to receiving help, given the putative role of OT in social bonding and attunement. To this end, we manipulated whether help was received from a same-sex interaction partner (confederate) versus a control condition, crossed with a double-blind administration of intranasal OT (vs. placebo), and examined subjective and observer-rated participant responses to help. We observed significant interactions between OT and the help manipulation. In the placebo condition, receiving help from the interaction partner compared with the control condition had negative consequences, such that participants reported greater negative affect and came to view themselves and their interaction partners more negatively after interacting together on several tasks. What is important, however, is that OT administration buffered against these negative subjective responses to receiving help. Further, outside observers rated participants who received OT administration as expressing greater happiness and gratitude in response to help, relative to those who received placebo. In sum, in the context of receiving help from a stranger, oxytocin administration fostered more positive affective and social responses. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  18. Thyroid stimulating hormone and serum, plasma, and platelet brain-derived neurotrophic factor during a 3-month follow-up in patients with major depressive disorder.

    Science.gov (United States)

    Baek, Ji Hyun; Kang, Eun-Suk; Fava, Maurizio; Mischoulon, David; Nierenberg, Andrew A; Lee, Dongsoo; Heo, Jung-Yoon; Jeon, Hong Jin

    2014-12-01

    Thyroid dysfunction and elevated thyroid stimulating hormone (TSH) are common in patients with depression. TSH might exert its function in the brain through blood levels of brain-derived neurotrophic factor (BDNF). BDNF decreases during depressed states and normalize after treatment. The gap is that the association between TSH and BDNF in patients with major depressive disorder (MDD) is unknown. We studied 105 subjects ≥18 years of age with MDD and measured serum, plasma, and platelet BDNF at baseline, 1 month and 3 months during antidepressant treatment. Other baseline measurements included hypothalamic-pituitary-thyroid axis hormones such as TSH, triiodothyronine (T3) and thyroxine (T4); hypothalamic-pituitary-adrenal (HPA) axis hormones and hypothalamic-pituitary-gonadal (HPG) axis hormones and prolactin. Linear mixed model effect analyses revealed that baseline TSH level was negatively associated with changes of serum BDNF from baseline to 3 months (F=7.58, p=0.007) after adjusting for age, sex, and body mass index, but was not associated with plasma and platelet BDNF. In contrast, T3 and T4, HPA axis hormones, HPG axis hormones, and prolactin were not associated with serum, plasma, or platelet BDNF levels. Patients in the highest quartile of TSH showed significantly lower serum BDNF than in the other quartiles (F=4.54, p=0.038), but no significant differences were found based on T3 and T4 levels. TSH was only measured at baseline. Higher TSH is associated with lower baseline and reduced the increase of serum BDNF levels during antidepressant treatment in patients with MDD. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Radioimmunoassay of urine oxytocin in man

    International Nuclear Information System (INIS)

    Zebidi, A.; Geelen, G.; Allevard, A.M.; Sempore, B.; Jarsaillon, E.; Meunier, C.; Gharib, C.

    1978-01-01

    A radioimmunoassay (RIA) for oxytocin (OT) in urine is described. 125 I-OT was prepared, and antibodies were raised in rabbits against OT coupled to bovine serumalbumine. This allowed us to set up a RIA for OT which limit of detection is 1.25 pg/tube (0.6 μU). The use of an extraction procedure using CG 50 Amberlite is essential. The recovery after extraction reaches 70.5 %. pH 5 is the optimum pH were urine samples must be stored. The superposition of the elution peak of endogenous OT on that of exogenous hormone is an argument in favour of the validity of such an extraction procedure. Daily urinary excretion of OT reaches 9.58 mU +- 3.48 in 18 healthy young men [fr

  20. The orgasmic history of oxytocin: Love, lust, and labor

    Directory of Open Access Journals (Sweden)

    Navneet Magon

    2011-01-01

    Full Text Available Oxytocin has been best known for its roles in female reproduction. It is released in large amounts during labor, and after stimulation of the nipples. It is a facilitator for childbirth and breastfeeding. However, recent studies have begun to investigate oxytocin′s role in various behaviors, including orgasm, social recognition, bonding, and maternal behaviors. This small nine amino acid peptide is now believed to be involved in a wide variety of physiological and pathological functions such as sexual activity, penile erection, ejaculation, pregnancy, uterine contraction, milk ejection, maternal behavior, social bonding, stress and probably many more, which makes oxytocin and its receptor potential candidates as targets for drug therapy. From an innocuous agent as an aid in labor and delivery, oxytocin has come a long way in being touted as the latest party drug. The hormone of labor during the course of the last 100 years has had multiple orgasms to be the hormone of love. Many more shall be seen in the times to come!

  1. Recovery from adolescent anorexia nervosa and associations with diurnal patterns of salivary stress hormones: a case report

    OpenAIRE

    Oskis, Andrea; Loveday, Catherine; Hucklebridge, Frank; Wood, David; Clow, Angela

    2012-01-01

    In the neurodevelopment of adolescent anorexia nervosa (AN), dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is proposed to be a central component. Furthermore, a therapeutic milieu focusing on affect regulation can contribute much to treatment, given the emotional processing difficulties associated with this disorder. Studies of HPA axis function following such specialist treatments for adolescent AN, however, are rare. This study describes the diurnal pattern of HPA axis acti...

  2. Oxytocin promotes intuitive rather than deliberated cooperation with the in-group

    NARCIS (Netherlands)

    Ten Velden, F.S.; Daughters, K.; De Dreu, C.K.W.

    A contribution to a special issue on Hormones and Human Competition. In intergroup settings, individuals prefer cooperating with their in-group, and sometimes derogate and punish out-groups. Here we replicate earlier work showing that such in-group bounded cooperation is conditioned by oxytocin and

  3. Alterations in the corticotropin-releasing hormone (CRH) neurocircuitry: Insights into post stroke functional impairments.

    Science.gov (United States)

    Barra de la Tremblaye, P; Plamondon, H

    2016-07-01

    Although it is well accepted that changes in the regulation of the hypothalamic-pituitary adrenal (HPA) axis may increase susceptibility to affective disorders in the general population, this link has been less examined in stroke patients. Yet, the bidirectional association between depression and cardiovascular disease is strong, and stress increases vulnerability to stroke. Corticotropin-releasing hormone (CRH) is the central stress hormone of the HPA axis pathway and acts by binding to CRH receptors (CRHR) 1 and 2, which are located in several stress-related brain regions. Evidence from clinical and animal studies suggests a role for CRH in the neurobiological basis of depression and ischemic brain injury. Given its importance in the regulation of the neuroendocrine, autonomic, and behavioral correlates of adaptation and maladaptation to stress, CRH is likely associated in the pathophysiology of post stroke emotional impairments. The goals of this review article are to examine the clinical and experimental data describing (1) that CRH regulates the molecular signaling brain circuit underlying anxiety- and depression-like behaviors, (2) the influence of CRH and other stress markers in the pathophysiology of post stroke emotional and cognitive impairments, and (3) context and site specific interactions of CRH and BDNF as a basis for the development of novel therapeutic targets. This review addresses how the production and release of the neuropeptide CRH within the various regions of the mesocorticolimbic system influences emotional and cognitive behaviors with a look into its role in psychiatric disorders post stroke. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Effects of the Adult Attachment Projective Picture System on oxytocin and cortisol blood levels in mothers

    Directory of Open Access Journals (Sweden)

    Sabrina Krause

    2016-12-01

    Full Text Available Oxytocin, a small neuropeptide of nine amino acids, has been characterized as the hormone of affiliation and is stimulated, for instance, in mothers when interacting with their offspring. Variations in maternal oxytocin levels were reported to predict differences in the quality of care provided by mothers. In this study, the Adult Attachment Projective Picture System (AAP as a valid measure to assess attachment representations was used as an activating attachment-related stimulus. We investigated whether the AAP induces a release of oxytocin in mothers with a secure attachment representation and a stress-related cortisol response in mothers with an insecure attachment representation. Therefore, pre-post effects of AAP administration on plasma oxytocin and serum cortisol levels were investigated in n = 44 mothers 3 months after parturition. Oxytocin levels increased from pre to post by the significant majority of 73% participants (p = .004 and cortisol decreased by the significant majority of 73% participants (p = .004. Interestingly, no association between alterations in oxytocin and cortisol were found; this suggests taking a model of two independent processes into considerations. These results show that the AAP test procedure induces an oxytocin response. Concerning the results within the four AAP representation subgroups, our hypothesis of a particularly strong increase in oxytocin in secure mothers was not confirmed; however, in secure mothers we observed a particularly strong decrease in cortisol, consistent with our hypotheses. Effect sizes are reported, allowing the replication of results in a larger study with sufficient sample size to draw final conclusions with respect to differences in OT and cortisol alterations depending on attachment representation. When interpreting the results, one should keep in mind that this study investigated lactating mothers. Thus, the generalizability of results is limited and future studies should

  5. Effects of the Adult Attachment Projective Picture System on Oxytocin and Cortisol Blood Levels in Mothers.

    Science.gov (United States)

    Krause, Sabrina; Pokorny, Dan; Schury, Katharina; Doyen-Waldecker, Cornelia; Hulbert, Anna-Lena; Karabatsiakis, Alexander; Kolassa, Iris-Tatjana; Gündel, Harald; Waller, Christiane; Buchheim, Anna

    2016-01-01

    Oxytocin, a small neuropeptide of nine amino acids, has been characterized as the "hormone of affiliation" and is stimulated, for instance, in mothers when interacting with their offspring. Variations in maternal oxytocin levels were reported to predict differences in the quality of care provided by mothers. In this study, the Adult Attachment Projective Picture System (AAP) as a valid measure to assess attachment representations was used as an activating attachment-related stimulus. We investigated whether the AAP induces a release of oxytocin in mothers with a secure attachment representation and a stress-related cortisol response in mothers with an insecure attachment representation. Therefore, pre-post effects of AAP administration on plasma oxytocin and serum cortisol levels were investigated in n = 44 mothers 3 months after parturition. Oxytocin levels increased from pre to post in the significant majority of 73% participants ( p = 0.004) and cortisol decreased in the significant majority of 73% participants ( p = 0.004). Interestingly, no association between alterations in oxytocin and cortisol were found; this suggests taking a model of two independent processes into considerations. These results show that the AAP test procedure induces an oxytocin response. Concerning the results within the four AAP representation subgroups, our hypothesis of a particularly strong increase in oxytocin in secure mothers was not confirmed; however, in secure mothers we observed a particularly strong decrease in cortisol. Effect sizes are reported, allowing the replication of results in a larger study with sufficient sample size to draw final conclusions with respect to differences in OT and cortisol alterations depending on attachment representation. When interpreting the results, one should keep in mind that this study investigated lactating mothers. Thus, the generalizability of results is limited and future studies should investigate non-lactating healthy females as well

  6. Effects of Intranasal Oxytocin on the Blood Oxygenation Level-Dependent Signal in Food Motivation and Cognitive Control Pathways in Overweight and Obese Men.

    Science.gov (United States)

    Plessow, Franziska; Marengi, Dean A; Perry, Sylvia K; Felicione, Julia M; Franklin, Rachel; Holmes, Tara M; Holsen, Laura M; Makris, Nikolaos; Deckersbach, Thilo; Lawson, Elizabeth A

    2018-02-01

    Recent research indicates that the hypothalamic neuropeptide hormone oxytocin is a key central nervous system factor in the regulation of food intake and weight. However, the mechanisms underlying the anorexigenic effects of oxytocin in humans are unknown and critical to study to consider oxytocin as a neurohormonal weight loss treatment. We performed a randomized, double-blind, placebo-controlled crossover study with single-dose intranasal oxytocin (24 IU) in ten overweight or obese, otherwise healthy men. Following oxytocin/placebo administration, participants completed an established functional magnetic resonance imaging food motivation paradigm. We hypothesized that oxytocin would reduce the blood oxygenation level-dependent (BOLD) signal to high-calorie food vs non-food visual stimuli in the ventral tegmental area (VTA), the origin of the mesolimbic dopaminergic reward system. Following oxytocin administration, compared to placebo, participants showed bilateral VTA hypoactivation to high-calorie food stimuli. A secondary exploratory whole-brain analysis revealed hypoactivation in additional hedonic (orbitofrontal cortex, insula, globus pallidus, putamen, hippocampus, and amygdala) and homeostatic (hypothalamus) food motivation and hyperactivation in cognitive control (anterior cingulate and frontopolar cortex) brain regions following oxytocin administration vs placebo. Oxytocin administration reduces the BOLD signal in reward-related food motivation brain regions, providing a potential neurobiological mechanism for the anorexigenic oxytocin effects in humans. Furthermore, our data indicate that oxytocin administration reduces activation in homeostatic and increases activation in cognitive control brain regions critically involved in regulating food intake and resolving affective conflict, respectively. Future studies are required to link these changes in brain activation to oxytocin effects on food intake and weight.

  7. Salubrious effects of oxytocin on social stress-induced deficits

    OpenAIRE

    Smith, Adam S.; Wang, Zuoxin

    2011-01-01

    Social relationships are a fundamental aspect of life, affecting social, psychological, physiological, and behavioral functions. While social interactions can attenuate stress and promote health, disruption, confrontations, isolation, or neglect in the social environment can each be major stressors. Social stress can impair the basal function and stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis, impairing function of multiple biological systems and posing a risk to m...

  8. Syntheses of DL-[2-13C]leucine and its use in the preparation of [3-DL-[2-13C]leucine]oxytocin and [8-DL-[2-13C]leucine]oxytocin

    International Nuclear Information System (INIS)

    Viswanatha, V.; Larsen, B.; Hruby, V.J.

    1979-01-01

    DL-[2- 13 C]Leucine was prepared by condensing the sodium salt of ethyl acetamido-[2- 13 C]cyanoacetate with isobutylbromide in hexamethylphosphoroustriamide followed by acid hydrolysis. N-BOC-DL-[2- 13 C]Leucine was prepared and incorporated into [8-DL-[2- 13 C]leucine]oxytocin by total synthesis. The 13 C-labeled hormone derivative [8-[2- 13 C]leucine]oxytocin was separated from its 8-position diastereoisomer by partition chromatography. The specifically 13 C-labeled peptide hormone diastereoisomeric analog [3-DL-[2- 13 C]leucine]oxytocin also was prepared by solid phase peptide synthesis. No suitable solvent system for partition chromatography separation of the latter diastereoisomeric peptide mixture could be found. However an excellent preparative separation of the diastereoisomers could be obtained by reverse phase high pressure liquid chromatography on a partisil 10 M9 ODS column using the solvent system 0.05 M ammonium acetate (pH 4.0), acetonitrile (81:19, v/v) to give pure [3-[2- 13 C]leucine]oxytocin and [3-D-[2- 13 C]leucine]oxytocin. An excellent separation of [8-[2- 13 C]leucine]oxytocin and the corresponding delata-D-leucine diastereoisomer derivative could also be accomplished by high pressure liquid chromatography. (author)

  9. Parent observed neuro-behavioral and pro-social improvements with oxytocin following surgical resection of craniopharyngioma.

    Science.gov (United States)

    Cook, Naomi; Miller, Jennifer; Hart, John

    2016-08-01

    Social and emotional impairment, school dysfunction, and neurobehavioral impairment are highly prevalent in survivors of childhood craniopharyngioma and negatively affect quality of life. As surgical resection of craniopharyngioma typically impairs hypothalamic/pituitary function, it has been postulated that perhaps post-operative deficiency of the hormone oxytocin may be the etiology of social/emotional impairment. Research on the benefits of oxytocin treatment as a hormone facilitating social interaction is well established. However, no research has yet been conducted on patients with known pituitary/hypothalamic dysfunction due to structural lesions or surgery. This case report investigates the effects of oxytocin therapy on a youngster with pituitary/hypothalamic dysfunction after craniopharyngioma removal. In this individual, treatment with low dose intranasal oxytocin resulted in increased desire for socialization and improvement in affection towards family. In light of these findings, the authors believe that further research into the potential benefits of intranasal oxytocin therapy for patients with panhypopituitarism is necessary to determine whether a broader population may also benefit from intranasal oxytocin therapy.

  10. Evaluation of Basal Serum Adrenocorticotropic Hormone and Cortisol Levels and Their Relationship with Nonalcoholic Fatty Liver Disease in Male Patients with Idiopathic Hypogonadotropic Hypogonadism.

    Science.gov (United States)

    Wang, Wen-Bo; She, Fei; Xie, Li-Fang; Yan, Wen-Hua; Ouyang, Jin-Zhi; Wang, Bao-An; Ma, Hang-Yun; Zang, Li; Mu, Yi-Ming

    2016-05-20

    Prolonged gonadal hormone deficiency in patients with idiopathic hypogonadotropic hypogonadism (IHH) may produce adverse effects on the endocrine homeostasis and metabolism. This study aimed to compare basal serum adrenocorticotropic hormone (ACTH) and cortisol levels between male IHH patients and healthy controls. Moreover, this study compared the basal hypothalamic-pituitary-adrenal (HPA) axis in patients with and without nonalcoholic fatty liver disease (NAFLD), and also evaluated the relationship between basal HPA axis and NAFLD in male IHH patients. This was a retrospective case-control study involving 75 Chinese male IHH patients (mean age 21.4 ± 3.8 years, range 17-30 years) and 135 healthy controls after matching for gender and age. All subjects underwent physical examination and blood testing for serum testosterone, luteinizing hormone, follicle-stimulating hormone, ACTH, and cortisol and biochemical tests. Higher basal serum ACTH levels (8.25 ± 3.78 pmol/L vs. 6.97 ± 2.81 pmol/L) and lower cortisol levels (366.70 ± 142.48 nmol/L vs. 452.82 ± 141.53 nmol/L) were observed in male IHH patients than healthy subjects (all pIHH patients also showed higher metabolism parameters and higher prevalence rate of NAFLD (34.9% vs. 4.4%) than the controls (all P IHH patients with NAFLD than those without NAFLD (all P IHH patients. Furthermore, NAFLD was independently associated with ACTH levels in male IHH patients by multiple linear regression analysis. The male IHH patients showed higher basal serum ACTH levels and lower cortisol levels than matched healthy controls. NAFLD was an independent associated factor for ACTH levels in male IHH patients. These preliminary findings provided evidence of the relationship between basal serum ACTH and NAFLD in male IHH patients.

  11. In etanercept-treated psoriatic arthritis patients clinical improvement correlated with an increase of serum cortisol relative to other adrenal hormones.

    Science.gov (United States)

    Atzeni, F; Sarzi-Puttini, P; DePortu, S; Cutolo, M; Carrabba, M; Straub, R H

    2008-01-01

    In patients with rheumatoid arthritis (RA), long-term therapy with anti-tumor necrosis factor (TNF) antibodies sensitizes the pituitary gland and improves adrenal androgen secretion in prednisolone-naïve patients. However, whether this is similar in psoriatic arthritis (PsA) is not known. The aim of this study was to assess the effect of 12 weeks of etanercept treatment upon the function of the HPA axis in patients with PsA. Eleven prednisolone-naïve patients (mean age 47.3+/-8.9 years) with PsA were included. We measured serum levels of adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17OHP), cortisol, and androstenedione (ASD), at baseline and at 4 and 12 weeks after initiation of anti-TNF therapy (etanercept, 50 mg every week as a single dose by sc. injection). Clinical improvement was assessed using the Disease Activity Score-28 (DAS-28). Mean levels of serum ACTH, serum cortisol, serum 17OHP and serum ASD did not markedly change during 12 weeks of etanercept treatment. Similarly, the ratio of serum cortisol divided by serum ACTH did not change during 12 weeks of anti-TNF treatment. However, an increase of serum cortisol relative to serum 17OHP or ASD was related to clinical improvement. This indicates that improvement was linked to higher serum cortisol levels relative to others adrenal hormones. This is the first study to demonstrate baseline serum levels and the course of HPA axis-related hormones in patients with PsA. An increase of serum cortisol relative to others adrenocortical hormones (i.e., androstenedione and ACTH) was accompanied by clinical improvement.

  12. Oxytocin and Aggression.

    Science.gov (United States)

    de Jong, Trynke R; Neumann, Inga D

    2017-09-02

    The neuropeptide oxytocin (OT) has a solid reputation as a facilitator of social interactions such as parental and pair bonding, trust, and empathy. The many results supporting a pro-social role of OT have generated the hypothesis that impairments in the endogenous OT system may lead to antisocial behavior, most notably social withdrawal or pathological aggression. If this is indeed the case, administration of exogenous OT could be the "serenic" treatment that psychiatrists have for decades been searching for.In the present review, we list and discuss the evidence for an endogenous "hypo-oxytocinergic state" underlying aggressive and antisocial behavior, derived from both animal and human studies. We furthermore examine the reported effects of synthetic OT administration on aggression in rodents and humans.Although the scientific findings listed in this review support, in broad lines, the link between a down-regulated or impaired OT system activity and increased aggression, the anti-aggressive effects of synthetic OT are less straightforward and require further research. The rather complex picture that emerges adds to the ongoing debate questioning the unidirectional pro-social role of OT, as well as the strength of the effects of intranasal OT administration in humans.

  13. Oxytocin and social affiliation in humans.

    Science.gov (United States)

    Feldman, Ruth

    2012-03-01

    A conceptual model detailing the process of bio-behavioral synchrony between the online physiological and behavioral responses of attachment partners during social contact is presented as a theoretical and empirical framework for the study of affiliative bonds. Guided by an ethological behavior-based approach, we suggest that micro-level social behaviors in the gaze, vocal, affective, and touch modalities are dynamically integrated with online physiological processes and hormonal response to create dyad-specific affiliations. Studies across multiple attachments throughout life are presented and demonstrate that the extended oxytocin (OT) system provides the neurohormonal substrate for parental, romantic, and filial attachment in humans; that the three prototypes of affiliation are expressed in similar constellations of social behavior; and that OT is stable over time within individuals, is mutually-influencing among partners, and that mechanisms of cross-generation and inter-couple transmission relate to coordinated social behavior. Research showing links between peripheral and genetic markers of OT with concurrent parenting and memories of parental care; between administration of OT to parent and infant's physiological readiness for social engagement; and between neuropeptides and the online synchrony of maternal and paternal brain response in social-cognitive and empathy networks support the hypothesis that human attachment develops within the matrix of biological attunement and close behavioral synchrony. The findings have conceptual implications for the study of inter-subjectivity as well as translational implications for the treatment of social disorders originating in early childhood, such as autism spectrum disorders, or those associated with disruptions to early bonding, such as postpartum depression or child abuse and neglect. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior. Copyright © 2012 Elsevier Inc. All

  14. The neuroenergetics of stress hormones in the hippocampus and implications for memory

    Science.gov (United States)

    Osborne, Danielle M.; Pearson-Leary, Jiah; McNay, Ewan C.

    2015-01-01

    Acute stress causes rapid release of norepinephrine (NE) and glucocorticoids (GCs), both of which bind to hippocampal receptors. This release continues, at varying concentrations, for several hours following the stressful event, and has powerful effects on hippocampally-dependent memory that generally promote acquisition and consolidation while impairing retrieval. Several studies have characterized the brain's energy usage both at baseline and during memory processing, but there are few data on energy requirements of memory processes under stressful conditions. Because memory is enhanced by emotional arousal such as during stress, it is likely that molecular memory processes under these conditions differ from those under non-stressful conditions that do not activate the hypothalamic-pituitary-adrenal (HPA) axis. Mobilization of peripheral and central energy stores during stress may increase hippocampal glucose metabolism that enhances salience and detail to facilitate memory enhancement. Several pathways activated by the HPA axis affect neural energy supply and metabolism, and may also prevent detrimental damage associated with chronic stress. We hypothesize that alterations in hippocampal metabolism during stress are key to understanding the effects of stress hormones on hippocampally-dependent memory formation. Second, we suggest that the effects of stress on hippocampal metabolism are bi-directional: within minutes, NE promotes glucose metabolism, while hours into the stress response GCs act to suppress metabolism. These bi-directional effects of NE and GCs on glucose metabolism may occur at least in part through direct modulation of glucose transporter-4. In contrast, chronic stress and prolonged elevation of hippocampal GCs cause chronically suppressed glucose metabolism, excitotoxicity and subsequent memory deficits. PMID:25999811

  15. The Neuroenergetics of Stress Hormones in the Hippocampus and Implications for Memory

    Directory of Open Access Journals (Sweden)

    Danielle eOsborne

    2015-05-01

    Full Text Available Acute stress causes rapid release of norepinephrine (NE and glucocorticoids (GCs, both of which bind to hippocampal receptors. This release continues, at varying concentrations, for several hours following the stressful event, and has powerful effects on hippocampally-dependent memory that generally promote acquisition and consolidation while impairing retrieval. Several studies have characterized the brain's energy usage both at baseline and during memory processing, but there are few data on energy requirements of memory processes under stressful conditions. Because memory is enhanced by emotional arousal such as during stress, it is likely that molecular memory processes under these conditions differ from those under non-stressful conditions that do not activate the hypothalamic-pituitary-adrenal (HPA axis. Mobilization of peripheral and central energy stores during stress may increase hippocampal glucose metabolism that enhances salience and detail to facilitate memory enhancement. Several pathways activated by the HPA axis affect neural energy supply and metabolism, and may also prevent detrimental damage associated with chronic stress. We hypothesize that alterations in hippocampal metabolism during stress are key to understanding the effects of stress hormones on hippocampally-dependent memory formation. Second, we suggest that the effects of stress on hippocampal metabolism are bi-directional: within minutes, NE promotes glucose metabolism, while hours into the stress response GCs act to suppress metabolism. These bi-directional effects of NE and GCs on glucose metabolism may occur at least in part through direct modulation of glucose transporter-4. In contrast, chronic stress and prolonged elevation of hippocampal GCs cause chronically suppressed glucose metabolism, excitotoxicity and subsequent memory deficits.

  16. Ozone modifies the metabolic and endocrine response to glucose: Reproduction of effects with the stress hormone corticosterone.

    Science.gov (United States)

    Thomson, Errol M; Pilon, Shinjini; Guénette, Josée; Williams, Andrew; Holloway, Alison C

    2018-03-01

    Air pollution is associated with increased incidence of metabolic disease (e.g. metabolic syndrome, obesity, diabetes); however, underlying mechanisms are poorly understood. Air pollutants increase the release of stress hormones (human cortisol, rodent corticosterone), which could contribute to metabolic dysregulation. We assessed acute effects of ozone, and stress axis involvement, on glucose tolerance and on the metabolic (triglyceride), endocrine/energy regulation (insulin, glucagon, GLP-1, leptin, ghrelin, corticosterone), and inflammatory/endothelial (TNF, IL-6, VEGF, PAI-1) response to exogenous glucose. Male Fischer-344 rats were exposed to clean air or 0.8 ppm ozone for 4 h in whole body chambers. Hypothalamic-pituitary-adrenal (HPA) axis involvement in ozone effects was tested through subcutaneous administration of the glucocorticoid synthesis inhibitor metyrapone (50 mg/kg body weight), corticosterone (10 mg/kg body weight), or vehicle (40% propylene glycol) prior to exposure. A glucose tolerance test (2 g/kg body weight glucose) was conducted immediately after exposure, with blood samples collected at 0, 30, 60, 90, and 120 min. Ozone exposure impaired glucose tolerance, an effect accompanied by increased plasma triglycerides but no impairment of insulin release. Ozone diminished glucagon, GLP-1, and ghrelin responses to glucose, but did not significantly impact inflammatory/endothelial analytes. Metyrapone reduced corticosterone but increased glucose and triglycerides, complicating evaluation of the impact of glucocorticoid inhibition. However, administration of corticosterone reproduced the profile of ozone effects, supporting a role for the HPA axis. The results show that ozone-dependent changes in glucose tolerance are accompanied by altered metabolic and endocrine responses to glucose challenge that are reproduced by exogenous stress hormone. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

  17. Oxytocin promotes intuitive rather than deliberated cooperation with the in-group.

    Science.gov (United States)

    Ten Velden, Femke S; Daughters, Katie; De Dreu, Carsten K W

    2017-06-01

    A contribution to a special issue on Hormones and Human Competition. In intergroup settings, individuals prefer cooperating with their in-group, and sometimes derogate and punish out-groups. Here we replicate earlier work showing that such in-group bounded cooperation is conditioned by oxytocin and extend it by showing that oxytocin-motivated in-group cooperation is intuitive rather than deliberated. Healthy males (N=65) and females (N=129) self-administered intranasal placebo or 24IU oxytocin in a double-blind placebo-controlled between-subjects design, were assigned to a three-person in-group (that faced a 3-person out-group), and given an endowment from which they could contribute to a within-group pool (benefitting the in-group), and/or to a between-group pool (benefitting the in-group and punishing the out-group). Prior to decision-making, participants performed a Stroop Interference task that was either cognitively taxing, or not. Cognitively taxed individuals kept less to themselves and contributed more to the within-group pool. Furthermore, participants receiving placebo contributed more to the within-group pool when they were cognitively taxed rather than not; those receiving oxytocin contributed to the within-group pool regardless of cognitive taxation. Neither taxation nor treatment influenced contributions to the between-group pool, and no significant sex differences were observed. It follows that in intergroup settings (i) oxytocin increases in-group bounded cooperation, (ii) oxytocin neither reduces nor increases out-group directed spite, and (iii) oxytocin-induced in-group cooperation is independent of cognitive taxation and, therefore, likely to be intuitive rather than consciously deliberated. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Intranasal oxytocin reduces social perception in women: Neural activation and individual variation.

    Science.gov (United States)

    Hecht, Erin E; Robins, Diana L; Gautam, Pritam; King, Tricia Z

    2017-02-15

    Most intranasal oxytocin research to date has been carried out in men, but recent studies indicate that females' responses can differ substantially from males'. This randomized, double-blind, placebo-controlled study involved an all-female sample of 28 women not using hormonal contraception. Participants viewed animations of geometric shapes depicting either random movement or social interactions such as playing, chasing, or fighting. Probe questions asked whether any shapes were "friends" or "not friends." Social videos were preceded by cues to attend to either social relationships or physical size changes. All subjects received intranasal placebo spray at scan 1. While the experimenter was not blinded to nasal spray contents at Scan 1, the participants were. Scan 2 followed a randomized, double-blind design. At scan 2, half received a second placebo dose while the other half received 24 IU of intranasal oxytocin. We measured neural responses to these animations at baseline, as well as the change in neural activity induced by oxytocin. Oxytocin reduced activation in early visual cortex and dorsal-stream motion processing regions for the social > size contrast, indicating reduced activity related to social attention. Oxytocin also reduced endorsements that shapes were "friends" or "not friends," and this significantly correlated with reduction in neural activation. Furthermore, participants who perceived fewer social relationships at baseline were more likely to show oxytocin-induced increases in a broad network of regions involved in social perception and social cognition, suggesting that lower social processing at baseline may predict more positive neural responses to oxytocin. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Social support, oxytocin, and PTSD

    NARCIS (Netherlands)

    Olff, Miranda; Koch, Saskia B. J.; Nawijn, Laura; Frijling, Jessie L.; van Zuiden, Mirjam; Veltman, Dick J.

    2014-01-01

    A lack of social support and recognition by the environment is one of the most consistent risk factors for posttraumatic stress disorder (PTSD), and PTSD patients will recover faster with proper social support. The oxytocin system has been proposed to underlie beneficial effects of social support as

  20. Food sharing is linked to urinary oxytocin levels and bonding in related and unrelated wild chimpanzees

    Science.gov (United States)

    Wittig, Roman M.; Crockford, Catherine; Deschner, Tobias; Langergraber, Kevin E.; Ziegler, Toni E.; Zuberbühler, Klaus

    2014-01-01

    Humans excel in cooperative exchanges between unrelated individuals. Although this trait is fundamental to the success of our species, its evolution and mechanisms are poorly understood. Other social mammals also build long-term cooperative relationships between non-kin, and recent evidence shows that oxytocin, a hormone involved in parent–offspring bonding, is likely to facilitate non-kin as well as kin bonds. In a population of wild chimpanzees, we measured urinary oxytocin levels following a rare cooperative event—food sharing. Subjects showed higher urinary oxytocin levels after single food-sharing events compared with other types of social feeding, irrespective of previous social bond levels. Also, urinary oxytocin levels following food sharing were higher than following grooming, another cooperative behaviour. Therefore, food sharing in chimpanzees may play a key role in social bonding under the influence of oxytocin. We propose that food-sharing events co-opt neurobiological mechanisms evolved to support mother–infant bonding during lactation bouts, and may act as facilitators of bonding and cooperation between unrelated individuals via the oxytocinergic system across social mammals. PMID:24430853

  1. The association between oxytocin and social capital.

    Directory of Open Access Journals (Sweden)

    Takeo Fujiwara

    Full Text Available BACKGROUND: Oxytocin is known to be related to social behaviors, including trust. However, few studies have investigated the association between oxytocin levels and social capital. Thus, we tested the hypothesis that endogenous oxytocin levels are positively associated with social capital. We also considered whether the association differed across gender because previous studies have shown differential effects of OT on social behaviors depending on gender. METHODS: We recruited a convenience sample of 50 women and 31 men in Japan via community sampling from whom we obtained urine sample with which to measure oxytocin levels. Individual-level cognitive social capital (social trust and mutual aid and structural social capital (community participation were assessed using a questionnaire. We used multivariate regression, adjusted for covariates (age, number of children, self-rated health, and education, and stratified by gender to consider associations between oxytocin and social capital. RESULTS: Among women, oxytocin was inversely associated with social trust and mutual aid (p<0.05. However, women participating in only 1 organization in the community showed higher oxytocin than women who participated in either no organizations (p<0.05 or 2 or more organization (i.e. inverse-U shape association. Among men, no association was observed between oxytocin and either form of cognitive and structural social capital. CONCLUSION: Women who perceived low cognitive social capital showed higher oxytocin levels, while structural social capital showed inverse-U shape association with oxytocin. No association between oxytocin and social capital was found among men. Further study is needed to elucidate why oxytocin was inversely associated with cognitive social capital only among women.

  2. Oxytocin and potential benefits for obesity treatment.

    Science.gov (United States)

    Olszewski, Pawel K; Klockars, Anica; Levine, Allen S

    2017-10-01

    Laboratory animal experiments have consistently shown that oxytocin causes early termination of food intake, thereby promoting a decrease in body weight in a long term. Recent studies have also assessed some of oxytocin's effects on appetite and energy balance in humans. The present study examines the findings of the key basic research and of the few clinical studies published thus far in the context of potential benefits and challenges stemming from the use of oxytocin in obese patients. Basic research indicates the involvement of oxytocin in satiety, processing, in reducing a drive to eat for pleasure and because of psychosocial factors. Although the results of clinical studies are very scarce, they suggest that oxytocin administered intranasally in humans decreases energy-induced and reward-induced eating, supports cognitive control of food choices, and improves glucose homeostasis, and its effectiveness may be BMI dependent. Despite the wealth of basic research showing broad anorexigenic effects of oxytocin, clinical studies on oxytocin's therapeutic potential in obesity, are still in their infancy. Future implementation of oxytocin-based pharmacological strategies in controlling energy balance will likely depend on our ability to integrate diverse behavioral and metabolic effects of oxytocin in obesity treatment regimens.

  3. Oxytocin determination by radioimmunoassay in cattle. 1

    International Nuclear Information System (INIS)

    Schams, D.; Schmidt-Polex, B.; Kruse, V.

    1979-01-01

    A radioimmunoassay for oxytocin in cow plasma is described. Antisera were raised in rabbits against synthetic oxytocin coupled to bovine thyroglobulin. Iodinated oxytocin free of unlabelled oxytocin and most likely also free of diiodo-oxytocin was used as radioactive tracer. The tracer showed a high degree of purity, and was stable on storage. It could be used in the assay for 2-3 months. The assay showed very little cross-reactivity with vasopressin. Acetone was used for the extraction of oxytocin from plasma as well as from standards made of synthetic exytocin in pooled cow plasma. Inhibition curves obtained with plasma collected from cows at parturition were parallel to those obtained with the oxytocin standard preparation. The mean recovery of oxytocin added to cow plasma was 106% (SD=14). The within-assay coefficient of variation (CV) varied from 5.2 to 10.9%, and the between-assay CV was in the order of 13%. The assay sensitivity was 1 pg (0.5 μU) per tube, corresponding to 3 pg/ml plasma. Around the time of milking the plasma oxytocin profile showed a strong response to the preparation for milking, and a further effect related to the attachment of the teat cups of the milking machine. Peak concentrations were in the range of 15-50 pg/ml. During parturition there was a peak of oxytocin (65 pg/ml) coinciding with the expulsion phase. After this peak levels decreased by remained measurably elevated until the expulsion of the placenta. The plasma disappearance curve for immunoreactive oxutocin after the infusion of 100 IU oxytocin over a period of 1 h showed two components with apparent half-lives of 7-9 and 25 min, respectively. (author)

  4. Stress and immunological response of heifers divergently ranked for residual feed intake following an adrenocorticotropic hormone challenge.

    Science.gov (United States)

    Kelly, A K; Lawrence, P; Earley, B; Kenny, D A; McGee, M

    2017-01-01

    When an animal is exposed to a stressor, metabolic rate, energy consumption and utilisation increase primarily through activation of the hypothalamic-pituitary-adrenal (HPA) axis. Changes to partitioning of energy by an animal are likely to influence the efficiency with which it is utilised. Therefore, this study aimed to determine the physiological stress response to an exogenous adrenocorticotropic hormone (ACTH) challenge in beef heifers divergently ranked on phenotypic residual feed intake (RFI). Data were collected on 34 Simmental weaning beef heifers the progeny of a well characterized and divergently bred RFI suckler beef herd. Residual feed intake was determined on each animal during the post-weaning stage over a 91-day feed intake measurement period during which they were individually offered adlibitum grass silage and 2 kg of concentrate per head once daily. The 12 highest [0.34 kg DM/d] and 12 lowest [-0.48 kg DM/d] ranking animals on RFI were selected for use in this study. For the physiological stress challenge heifers (mean age 605 ± 13 d; mean BW 518 ± 31.4 kg) were fitted aseptically with indwelling jugular catheters to facilitate intensive blood collection. The response of the adrenal cortex to a standardised dose of ACTH (1.98 IU/kg metabolic BW 0.75 ) was examined. Serial blood samples were analysed for plasma cortisol, ACTH and haematology variables. Heifers differing in RFI did not differ ( P  = 0.59) in ACTH concentrations. Concentration of ACTH peaked ( P  response than Low RFI from 40 min to 150 min relative to ACTH administration. Cortisol response was positively associated with RFI status ( r  = 0.32; P  responsiveness of the HPA axis is likely to contribute to appreciable variation in the efficiency feed utilisation of cattle.

  5. Oxytocin biotransformation in the rat limbic brain

    NARCIS (Netherlands)

    Burbach, J.P.H.; Schotman, P.; Kloet, E.R. de

    2006-01-01

    Two peptide fragments of oxytocin were isolated by high-pressure liquid chromatography from digests of oxytocin obtained after exposure to a SPM preparation of the rat limbic brain. The structures of these peptides, being Gln-Asn-Cys(O)x-Pro-Leu-GlyNH2 and Gln-Asn-Cys(-S-S-Cys)-Pro-Leu-GlyNH2, were

  6. Social condition and oxytocin neuron number in the hypothalamus of naked mole-rats (Heterocephalus glaber).

    Science.gov (United States)

    Mooney, S J; Holmes, M M

    2013-01-29

    The naked mole-rat is a subterranean colonial rodent. In each colony, which can grow to as many as 300 individuals, there is only one female and 1-3 males that are reproductive and socially dominant. The remaining animals are reproductively suppressed subordinates that contribute to colony survival through their cooperative behaviors. Oxytocin is a peptide hormone that has shown relatively widespread effects on prosocial behaviors in other species. We examined whether social status affects the number of oxytocin-immunoreactive neurons in the paraventricular nucleus and the supraoptic nucleus by comparing dominant breeding animals to subordinate non-breeding workers from intact colonies. We also examined these regions in subordinate animals that had been removed from their colony and paired with an opposite- or same-sex conspecific for 6 months. Stereological analyses indicated that subordinates had significantly more oxytocin neurons in the paraventricular nucleus than breeders. Animals in both opposite- and same-sex pairs showed a decreased oxytocin neuron number compared to subordinates suggesting that status differences may be due to social condition rather than the reproductive activity of the animal per se. The effects of social status appear to be region specific as no group differences were found for oxytocin neuron number in the supraoptic nucleus. Given that subordinate naked mole-rats are kept reproductively suppressed through antagonism by the queen, we speculate that status differences are due either to oxytocin's anxiolytic properties to combat the stress of this antagonism or to its ability to promote the prosocial behaviors of subordinates. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. The effect of oxytocin on group formation and strategic thinking in men.

    Science.gov (United States)

    Aydogan, Gökhan; Jobst, Andrea; Loy, Fabian; Dehning, Sandra; Zill, Peter; Müller, Norbert; Kocher, Martin

    2018-04-01

    Decision-making in groups is a remarkable and decisive element of human societies. Humans are able to organize themselves in groups, engage in collaborative decision-making processes and arrive at a binding agreement, even in the absence of unanimous consent. However, the transfer of decision-making autonomy requires a willingness to deliberately expose oneself to the decisions of others. A lack of trust in the abilities of others or of the underlying decision-making process, i.e. public trust, can lead to a breakdown of organizations in political or economic domains. Recent studies indicate that the biological basis of trust on an individual level is related to Oxytocin, an endogenous neuropeptide and hormone, which is also associated with pro-social behavior and positive conflict resolution. However, little is known about the effects of Oxytocin on the inclination of individuals to form or join groups and to deliberately engage in collaborative decision-making processes. Here, we show that intranasal administration of Oxytocin (n = 60) compared to placebo (n = 60) in males causes an adverse effect on the choice for forming groups in the presence of a competitive environment. In particular, Oxytocin negatively affects the willingness to work collaboratively in a p-Beauty contest game, whereas the effect is most pronounced for participants with relatively high strategic sophistication. Since our data provide initial evidence that Oxytocin has a positive effect on strategic thinking and performance in the p-Beauty contest game, we argue that the adverse effect on group formation might be rooted in an enhanced strategic sophistication of participants treated with Oxytocin. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Associative and sensorimotor learning for parenting involves mirror neurons under the influence of oxytocin.

    Science.gov (United States)

    Ho, S Shaun; Macdonald, Adam; Swain, James E

    2014-04-01

    Mirror neuron-based associative learning may be understood according to associative learning theories, in addition to sensorimotor learning theories. This is important for a comprehensive understanding of the role of mirror neurons and related hormone modulators, such as oxytocin, in complex social interactions such as among parent-infant dyads and in examples of mirror neuron function that involve abnormal motor systems such as depression.

  9. Associative and sensorimotor learning for parenting involves mirror neurons under the influence of oxytocin

    OpenAIRE

    Ho, S. Shaun; MacDonald, Adam; Swain, James E.

    2014-01-01

    Mirror neuron–based associative learning may be understood according to associative learning theories, in addition to sensorimotor learning theories. This is important for a comprehensive understanding of the role of mirror neurons and related hormone modulators, such as oxytocin, in complex social interactions such as among parent–infant dyads and in examples of mirror neuron function that involve abnormal motor systems such as depression.

  10. Oxytocin and Estrogen Receptor β in the Brain: An Overview

    OpenAIRE

    Acevedo-Rodriguez, Alexandra; Mani, Shaila K.; Handa, Robert J.

    2015-01-01

    Oxytocin is a neuropeptide synthesized primarily by neurons of the paraventricular and supraoptic nuclei of the hypothalamus. These neurons have axons that project into the posterior pituitary and release oxytocin into the bloodstream to promote labor and lactation; however, oxytocin neurons also project to other brain areas where it plays a role in numerous brain functions. Oxytocin binds to the widely expressed oxytocin receptor, and, in doing so, it regulates homeostatic processes, social ...

  11. Neurohypophyseal hormones: novel actors of striated muscle development and homeostasis

    Directory of Open Access Journals (Sweden)

    Alessandra Costa

    2014-09-01

    Full Text Available Since the 1980's, novel functional roles of the neurohypophyseal hormones vasopressin and oxytocin have emerged. Several studies have investigated the effects of these two neurohormones on striated muscle tissues, both in vitro and in vivo. The effects of vasopressin on skeletal myogenic cells, developing muscle and muscle homeostasis have been documented. Oxytocin appears to have a greater influence on cardiomyocite differentiation and heart homeostasis. This review summarizes the studies on these novel roles of the two neurohypophyseal hormones, and open the possibility of new therapeutic approaches for diseases affecting striated muscle.

  12. Sex differences and ovarian hormones in animal models of drug dependence.

    Science.gov (United States)

    Carroll, Marilyn E; Anker, Justin J

    2010-06-01

    Increasing evidence indicates the presence of sex differences in many aspects of drug abuse. Most studies reveal that females exceed males during the initiation, escalation, extinction, and reinstatement (relapse) of drug-seeking behavior, but males are more sensitive than females to the aversive effects of drugs such as drug withdrawal. Findings from human and animal research indicate that circulating levels of ovarian steroid hormones account for these sex differences. Estrogen (E) facilitates drug-seeking behavior, while progesterone (P) and its metabolite, allopregnanalone (ALLO), counteract the effects of E and reduce drug seeking. Estrogen and P influence other behaviors that are affiliated with drug abuse such as drug-induced locomotor sensitization and conditioned place preference. The enhanced vulnerability to drug seeking in females vs. males is also additive with the other risk factors for drug abuse (e.g., adolescence, sweet preference, novelty reactivity, and impulsivity). Finally, treatment studies using behavioral or pharmacological interventions, including P and ALLO, also indicate that females show greater treatment effectiveness during several phases of the addiction process. The neurobiological basis of sex differences in drug abuse appears to be genetic and involves the influence of ovarian hormones and their metabolites, the hypothalamic pituitary adrenal (HPA) axis, dopamine (DA), and gamma-hydroxy-butyric acid (GABA). Overall, sex and hormonal status along with other biological risk factors account for a continuum of addiction-prone and -resistant animal models that are valuable for studying drug abuse prevention and treatment strategies. Copyright 2009. Published by Elsevier Inc.

  13. Oxytocin determination by radioimmunoassay in cattle. 2

    International Nuclear Information System (INIS)

    Schams, D.; Baumann, G.; Leidl, W.

    1982-01-01

    Oxytocin concentration in jugular vein blood was measured radioimmunologically with a detection limit of 3 pg/ml plasma in male and female cattle. Five bulls were tested; during mating a cow in oestrus with intromission and ejaculation, during mounting a dummy or another bull with ejaculation into an artificial vagina or during false mounts. No increase in oxytocin concentrations could be observed, but stimulation with an electro-ejaculator caused an increase ranging from 5-84 pg/ml after a latent period of 3-5 min. A similar response was observed in two cows following the same procedure. The contact with a bull, false mount or mating with intromission and ejaculation was not followed by a measurable oxytocin release in 5 test cows. The following stimulation techniques, massage of vulva and clitoris, massage of cervix and uterus per rectum, artificial insemination, introduction of a speculum into the vagina or insufflation of air into the vagina were performed with 5 cows and 5 heifers. Insufflation of air into the vagina was the most effective stimulus, eleciting an oxytocin release up to 588 pg/ml. All 5 heiers responded positively, as well as 4 cows in oestrus. The other manipulations cuased an oxytocin response mainly in heifers (whether in oestrus or dioestrus), whereas only one cow in oestrus responded with an oxytocin release. In general, oxytocin concentrations increase about 30-90 s after the start of the stimulus. (author)

  14. Oxytocin improves emotion recognition for older males.

    Science.gov (United States)

    Campbell, Anna; Ruffman, Ted; Murray, Janice E; Glue, Paul

    2014-10-01

    Older adults (≥60 years) perform worse than young adults (18-30 years) when recognizing facial expressions of emotion. The hypothesized cause of these changes might be declines in neurotransmitters that could affect information processing within the brain. In the present study, we examined the neuropeptide oxytocin that functions to increase neurotransmission. Research suggests that oxytocin benefits the emotion recognition of less socially able individuals. Men tend to have lower levels of oxytocin and older men tend to have worse emotion recognition than older women; therefore, there is reason to think that older men will be particularly likely to benefit from oxytocin. We examined this idea using a double-blind design, testing 68 older and 68 young adults randomly allocated to receive oxytocin nasal spray (20 international units) or placebo. Forty-five minutes afterward they completed an emotion recognition task assessing labeling accuracy for angry, disgusted, fearful, happy, neutral, and sad faces. Older males receiving oxytocin showed improved emotion recognition relative to those taking placebo. No differences were found for older females or young adults. We hypothesize that oxytocin facilitates emotion recognition by improving neurotransmission in the group with the worst emotion recognition. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Severity of eating disorder symptoms related to oxytocin receptor polymorphisms in anorexia nervosa.

    Science.gov (United States)

    Acevedo, Summer F; Valencia, Celeste; Lutter, Michael; McAdams, Carrie J

    2015-08-30

    Oxytocin is a peptide hormone important for social behavior and differences in psychological traits have been associated with variants of the oxytocin receptor gene in healthy people. We examined whether single nucleotide polymorphisms (SNPs) of the oxytocin receptor gene (OXTR) correlated with clinical symptoms in women with anorexia nervosa, bulimia nervosa, and healthy comparison (HC) women. Subjects completed clinical assessments and provided DNA for analysis. Subjects were divided into four groups: HC, subjects currently with anorexia nervosa (AN-C), subjects with a history of anorexia nervosa but in long-term weight recovery (AN-WR), and subjects with bulimia nervosa (BN). Five SNPs of the oxytocin receptor were examined. Minor allele carriers showed greater severity in most of the psychiatric symptoms. Importantly, the combination of having had anorexia and carrying either of the A alleles for two SNPS in the OXTR gene (rs53576, rs2254298) was associated with increased severity specifically for ED symptoms including cognitions and behaviors associated both with eating and appearance. A review of psychosocial data related to the OXTR polymorphisms examined is included in the discussion. OXTR polymorphisms may be a useful intermediate endophenotype to consider in the treatment of patients with anorexia nervosa. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Oxytocin decreases colonic motility of cold water stressed rats via oxytocin receptors.

    Science.gov (United States)

    Yang, Xiao; Xi, Tao-Fang; Li, Yu-Xian; Wang, Hai-Hong; Qin, Ying; Zhang, Jie-Ping; Cai, Wen-Ting; Huang, Meng-Ting; Shen, Ji-Qiao; Fan, Xi-Min; Shi, Xuan-Zheng; Xie, Dong-Ping

    2014-08-21

    To investigate whether cold water intake into the stomach affects colonic motility and the involvement of the oxytocin-oxytocin receptor pathway in rats. Female Sprague Dawley rats were used and some of them were ovariectomized. The rats were subjected to gastric instillation with cold (0-4 °C, cold group) or room temperature (20-25 °C, control group) saline for 14 consecutive days. Colon transit was determined with a bead inserted into the colon. Colonic longitudinal muscle strips were prepared to investigate the response to oxytocin in vitro. Plasma concentration of oxytocin was detected by ELISA. Oxytocin receptor expression was investigated by Western blot analysis. Immunohistochemistry was used to locate oxytocin receptors. Colon transit was slower in the cold group than in the control group (P cold water intake (0.69 ± 0.08 vs 0.88 ± 0.16, P receptors were located in the myenteric plexus, and their expression was up-regulated in the cold group (P Cold water intake increased blood concentration of oxytocin, but this effect was attenuated in ovariectomized rats (286.99 ± 83.72 pg/mL vs 100.56 ± 92.71 pg/mL, P Cold water intake inhibits colonic motility partially through oxytocin-oxytocin receptor signaling in the myenteric nervous system pathway, which is estrogen dependent.

  17. Stability-indicating HPLC method for the determination of the stability of oxytocin parenteral solutions prepared in polyolefin bags.

    Science.gov (United States)

    Kaushal, G; Sayre, B E; Prettyman, T

    2012-02-01

    Oxytocin is very commonly used in clinical settings and is a nonapeptide hormone that stimulates the contraction of uterine smooth muscles. In this study the stability of extemporaneously compounded oxytocin solutions was investigated in polyolefin bags. The sterile preparations of oxytocin were compounded to the strength of 0.02 U/mL in accordance with United States Pharmacopeia (USP) standards. In order to carry out the stability testing of these parenteral products, the solutions were stored under three different temperature conditions of -20°C (frozen), 2-6°C (refrigerated), and 22-25°C (room temperature). Three solutions from each temperature were withdrawn and were assessed for stability on days 0, 7, 15, 21, and 30 as per the USP guidelines. The assay of oxytocin was examined by an HPLC method at each time point. No precipitation, cloudiness or color change was observed during this study at all temperatures. The assay content by HPLC revealed that oxytocin retains greater than at least 90% of the initial concentrations for 21 days. There was no significant change in pH and absorbance values for 21 days under all the conditions of storage. Oxytocin parenteral solutions in the final concentration of 0.02 U/mL and diluted in normal saline are stable for at least 30 days under frozen and refrigerated conditions for 30 days. At the room temperature, the oxytocin solutions were stable for at least 21 days. The stability analysis results show that the shelf-life of 21 days observed in this study was far better than their recommended expiration dates.

  18. Urinary and plasma oxytocin changes in response to MDMA or intranasal oxytocin administration.

    Science.gov (United States)

    Francis, Sunday M; Kirkpatrick, Matthew G; de Wit, Harriet; Jacob, Suma

    2016-12-01

    The neuropeptide oxytocin (OT) has received increased experimental attention for its putative role in both normal social functioning and several psychiatric disorders that are partially characterized by social dysfunction (e.g., autism spectrum disorders: ASD). Many human experimental studies measure circulating plasma levels of OT in order to examine the relationship between the hormone and behavior. Urinary OT (uOT) assays offer a simple, easy, and non-invasive method to measure peripheral hormone levels, but the correspondence between uOT and plasma OT (pOT) levels is unclear. Here, we conducted two within-subjects, double-blind studies exploring changes in uOT and pOT levels following administration of two drugs: MDMA, an oxytocin-releasing drug (Study 1), and intranasal oxytocin (INOT: Study 1 and 2). In Study 1, 14 adult participants (2 females) were each administered either oral 1.5mg/kg MDMA or 40IU INOT across two different study sessions. In Study 2, 10 male participants (adolescents and young adults) diagnosed with ASD received either 40IU INOT or placebo across two different sessions. In both studies, blood and urine samples were collected before and after drug administration at each study session. For Study 1, 10 participants provided valid plasma and urine samples for the MDMA session, and 8 provided valid samples for the INOT session. For Study 2, all 10 participants provided valid samples for both INOT and placebo sessions. Pre- and post-administration levels of pOT and uOT were compared. Additionally, correlations between percent change from baseline uOT and pOT levels were examined. Study 1: Plasma OT and uOT levels significantly increased after administration of MDMA and INOT. Furthermore, uOT levels were positively correlated with pOT levels following administration of MDMA (r=0.57, p=0.042) but not INOT (r=0.51, p=0.097). Study 2: There was a significant increase in uOT levels after administration of INOT, but not after administration of

  19. HPA Axis Function Alters Development of Working Memory in Boys with FXS

    Science.gov (United States)

    Scherr, Jessica F.; Hahn, Laura J.; Hooper, Stephen R.; Hatton, Deborah; Roberts, Jane E.

    2016-01-01

    The present study examines verbal working memory over time in boys with fragile X syndrome (FXS) compared to nonverbal mental-age (NVMA) matched, typically developing (TD) boys. Concomitantly, the relationship between cortisol—a physiological marker for stress—and verbal working memory performance over time is examined to understand the role of physiological mechanisms in cognitive development in FXS. Participants were assessed between one and three times over a 2-year time frame using two verbal working memory tests that differ in complexity: memory for words and auditory working memory with salivary cortisol collected at the beginning and end of each assessment. Multilevel modeling results indicate specific deficits over time on the memory for words task in boys with FXS compared to TD controls that is exacerbated by elevated baseline cortisol. Similar increasing rates of growth over time were observed for boys with FXS and TD controls on the more complex auditory working memory task, but only boys with FXS displayed an association of increased baseline cortisol and lower performance. This study highlights the benefit of investigations of how dynamic biological and cognitive factors interact and influence cognitive development over time. PMID:26760450

  20. Mathematical modeling of the hypothalamic–pituitary–adrenal gland (HPA) axis, including hippocampal mechanisms

    DEFF Research Database (Denmark)

    Andersen, Morten; Vinther, Frank; Ottesen, Johnny T.

    2013-01-01

    parameters, the system has a unique fixed point, and the system is globally stable. Therefore, solutions converge to the fixed point for all initial conditions. This is in agreement with cortisol levels returning to normal, after periods of mild stress, in healthy individuals.Perturbing parameters lead...

  1. Patient specific modeling of the HPA axis related to clinical diagnosis of depression

    DEFF Research Database (Denmark)

    Bangsgaard, Elisabeth; Ottesen, Johnny T.

    2017-01-01

    A novel model of the hypothalamic-pituitary-adrenal axis is presented. The axis is an endocrine system responsible for coping with stress and it is likely to be involved in depression. The dynamics of the system is studied and existence, uniqueness and positivity of the solution and the existence...... of an attracting trapping region are proved. The model is calibrated and compared to data for healthy and depressed subjects. A sensitivity analysis resulting in a set of identifiable physiological parameters is provided. A subset is selected for parameter estimation and a reduced version of the model is stated...... and an approximated version is discussed. The model is physiologically based, thus parameters are representative for gland functions or elimination processes. Hence the model may be used for pointing out pathologies by parameter estimation and hypothesis testing whereby it may be used as an objective and refined...

  2. Stress effects on mood, HPA axis, and autonomic response: comparison of three psychosocial stress paradigms.

    Directory of Open Access Journals (Sweden)

    Grace E Giles

    Full Text Available Extensive experimental psychology research has attempted to parse the complex relationship between psychosocial stress, mood, cognitive performance, and physiological changes. To do so, it is necessary to have effective, validated methods to experimentally induce psychosocial stress. The Trier Social Stress Test (TSST is the most commonly used method of experimentally inducing psychosocial stress, but it is resource intensive. Less resource intense psychosocial stress tasks include the Socially Evaluative Cold Pressor Task (SECPT and a computerized mental arithmetic task (MAT. These tasks effectively produce a physiological and psychological stress response and have the benefits of requiring fewer experimenters and affording data collection from multiple participants simultaneously. The objective of this study was to compare the magnitude and duration of these three experimental psychosocial stress induction paradigms. On each of four separate days, participants completed either a control non-stressful task or one of the three experimental stressors: the TSST, SECPT, or MAT. We measured mood, working memory performance, salivary cortisol and alpha-amylase (AA, and heart rate. The TSST and SECPT exerted the most robust effects on mood and physiological measures. TSST effects were generally evident immediately post-stress as well as 10- and 20-minutes after stress cessation, whereas SECPT effects were generally limited to the duration of the stressor. The stress duration is a key determinant when planning a study that utilizes an experimental stressor, as researchers may be interested in collecting dependent measures prior to stress cessation. In this way, the TSST would allow the investigator a longer window to administer tasks of interest.

  3. Depletion of FKBP51 in female mice shapes HPA axis activity

    NARCIS (Netherlands)

    Hoeijmakers, L.; Harbich, D.; Schmid, B.; Lucassen, P.J.; Wagner, K.V.; Schmidt, M.V.; Hartmann, J.

    2014-01-01

    Psychiatric disorders such as depressive disorders and posttraumatic stress disorder are a major disease burden worldwide and have a higher incidence in women than in men. However, the underlying mechanism responsible for the sex-dependent differences is not fully understood. Besides environmental

  4. HPA AXIS RESPONSE TO STRESS PREDICTS SHORT-TERM SNACK INTAKE IN OBESE WOMEN

    OpenAIRE

    Appelhans, Bradley M.; Pagoto, Sherry L.; Peters, Erica N.; Spring, Bonnie J.

    2009-01-01

    Prior research has linked heightened cortisol reactivity to stress with increased food consumption. This pilot study tested corollaries of the hypothesis that cortisol stress reactivity promotes obesity. Thirty-four lean and obese women completed an acute stress task and a non-stressful control task in counterbalanced order. Contrary to expectations, higher post-stress cortisol was associated with decreased post-stress snack intake in obese women but was unrelated to snack intake in lean wome...

  5. Mechanisms underlying the effects of prenatal psychosocial stress on child outcomes: beyond the HPA axis

    NARCIS (Netherlands)

    Beijers, R.; Buitelaar, J.K.; Weerth, C. de

    2014-01-01

    Accumulating evidence from preclinical and clinical studies indicates that maternal psychosocial stress and anxiety during pregnancy adversely affect child outcomes. However, knowledge on the possible mechanisms underlying these relations is limited. In the present paper, we review the most often

  6. High-end normal adrenocorticotropic hormone and cortisol levels are associated with specific cardiovascular risk factors in pediatric obesity: a cross-sectional study.

    Science.gov (United States)

    Prodam, Flavia; Ricotti, Roberta; Agarla, Valentina; Parlamento, Silvia; Genoni, Giulia; Balossini, Caterina; Walker, Gillian Elisabeth; Aimaretti, Gianluca; Bona, Gianni; Bellone, Simonetta

    2013-02-20

    The hypothalamic-pituitary-adrenal (HPA) axis, and in particular cortisol, has been reported to be involved in obesity-associated metabolic disturbances in adults and in selected populations of adolescents. The aim of this study was to investigate the association between morning adrenocorticotropic hormone (ACTH) and cortisol levels and cardiovascular risk factors in overweight or obese Caucasian children and adolescents. This cross-sectional study of 450 obese children and adolescents (aged 4 to 18 years) was performed in a tertiary referral center. ACTH, cortisol, cardiovascular risk factors (fasting and post-challenge glucose, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, and hypertension) and insulin resistance were evaluated. All analyses were corrected for confounding factors (sex, age, puberty, body mass index), and odds ratios were determined. ACTH and cortisol levels were positively associated with systolic and diastolic blood pressure, triglycerides, fasting glucose and insulin resistance. Cortisol, but not ACTH, was also positively associated with LDL-cholesterol. When adjusted for confounding factors, an association between ACTH and 2 h post-oral glucose tolerance test glucose was revealed. After stratification according to cardiovascular risk factors and adjustment for possible confounding factors, ACTH levels were significantly higher in subjects with triglycerides ≥90th percentile (P cortisol levels were found in subjects with blood pressure ≥95th percentile and LDL-cholesterol ≥90th percentile. Overall, the highest tertiles of ACTH (>5.92 pmol/l) and cortisol (>383.5 nmol/l) although within the normal range were associated with increases in cardiovascular risk factors in this population. In obese children and adolescents, high morning ACTH and cortisol levels are associated with cardiovascular risk factors. High ACTH levels are associated with high triglyceride levels and hyperglycemia

  7. Activation of Supraoptic Oxytocin Neurons by Secretin Facilitates Social Recognition.

    Science.gov (United States)

    Takayanagi, Yuki; Yoshida, Masahide; Takashima, Akihide; Takanami, Keiko; Yoshida, Shoma; Nishimori, Katsuhiko; Nishijima, Ichiko; Sakamoto, Hirotaka; Yamagata, Takanori; Onaka, Tatsushi

    2017-02-01

    Social recognition underlies social behavior in animals, and patients with psychiatric disorders associated with social deficits show abnormalities in social recognition. Oxytocin is implicated in social behavior and has received attention as an effective treatment for sociobehavioral deficits. Secretin receptor-deficient mice show deficits in social behavior. The relationship between oxytocin and secretin concerning social behavior remains to be determined. Expression of c-Fos in oxytocin neurons and release of oxytocin from their dendrites after secretin application were investigated. Social recognition was examined after intracerebroventricular or local injection of secretin, oxytocin, or an oxytocin receptor antagonist in rats, oxytocin receptor-deficient mice, and secretin receptor-deficient mice. Electron and light microscopic immunohistochemical analysis was also performed to determine whether oxytocin neurons extend their dendrites into the medial amygdala. Supraoptic oxytocin neurons expressed the secretin receptor. Secretin activated supraoptic oxytocin neurons and facilitated oxytocin release from dendrites. Secretin increased acquisition of social recognition in an oxytocin receptor-dependent manner. Local application of secretin into the supraoptic nucleus facilitated social recognition, and this facilitation was blocked by an oxytocin receptor antagonist injected into, but not outside of, the medial amygdala. In the medial amygdala, dendrite-like thick oxytocin processes were found to extend from the supraoptic nucleus. Furthermore, oxytocin treatment restored deficits of social recognition in secretin receptor-deficient mice. The results of our study demonstrate that secretin-induced dendritic oxytocin release from supraoptic neurons enhances social recognition. The newly defined secretin-oxytocin system may lead to a possible treatment for social deficits. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights

  8. Oxytocin reduces alcohol consumption in prairie voles.

    Science.gov (United States)

    Stevenson, J R; Wenner, S M; Freestone, D M; Romaine, C C; Parian, M C; Christian, S M; Bohidar, A E; Ndem, J R; Vogel, I R; O'Kane, C M

    2017-10-01

    Alcohol use disorder (AUD) negatively affects millions of people every year in the United States, and effective treatments for AUD are still needed. The neuropeptide oxytocin has shown promise for reducing alcohol drinking in mice and rats. Because oxytocin also plays a key role in complex prosocial behaviors like bonding and attachment, we tested the effect of oxytocin on alcohol drinking in prairie voles, a species that both consumes high amounts of alcohol and forms oxytocin dependent social bonds in a manner similar to humans. Oxytocin treatment (1.0, 3.0, and 10.0mg/kg, i.p.) reduced alcohol consumption in male and female prairie voles in animals that had access to 15% ethanol vs water every other day for 12 alcohol drinking sessions. In animals with continuous access to 15% alcohol and water, oxytocin (3.0mg/kg) reduced alcohol consumption only in the first hour of access after treatment, with no significant effects on consumption over the 24-hr period. In an open field locomotor test, oxytocin (1.0, 3.0, and 10.0mg/kg, i.p.) did not affect overall locomotor activity; however, ethanol (2g/kg, i.p.) increased locomotor activity in males and females, and produced anxiolytic effects (increased time in the center of an open field) in females only. Because prairie voles have been shown to match the alcohol consumption of their cage mate, we evaluated the relationship between cage mates' alcohol drinking. There was an overall pattern of social facilitation (consumption by one cage mate predicted consumption by the other cage mate); however, we found significant individual differences across cages in which many cages did not show significant matching, and, in some cases one cage mate's consumption negatively predicted the other cage mate's consumption. Overall, our data provide support for the potential of oxytocin as a treatment to reduce alcohol consumption. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Adrenergic and steroid hormone modulation of ozone-induced pulmonary injury and inflammation

    Science.gov (United States)

    Rationale: We have shown that acute ozone inhalation promotes activation of the sympathetic and hypothalamic-pituitary-adrenal (HPA) axis leading to release of cortisol and epinephrine from the adrenals. Adrenalectomy (ADREX) inhibits ozone-induced pulmonary vascular leakage and ...

  10. Adrenal gland hypofunction in active polymyalgia rheumatica. effect of glucocorticoid treatment on adrenal hormones and interleukin 6.

    Science.gov (United States)

    Cutolo, Maurizio; Straub, Rainer H; Foppiani, Luca; Prete, Camilla; Pulsatelli, Lia; Sulli, Alberto; Boiardi, Luigi; Macchioni, Pierluigi; Giusti, Massimo; Pizzorni, Carmen; Seriolo, Bruno; Salvarani, Carlo

    2002-04-01

    To evaluate hypothalamic-pituitary-adrenal (HPA) axis function in patients with recent onset polymyalgia rheumatica (PMR) not previously treated with glucocorticoids; and to detect possible correlations between adrenal hormone levels, interleukin 6 (IL-6), and other acute phase reactants at baseline and during 12 months of glucocorticoid treatment. Forty-one PMR patients of both sexes with recent onset disease and healthy sex and age matched controls were enrolled into a longitudinal study. Patients were monitored for serum cortisol, dehydroepiandrosterone sulfate (DHEAS), androstenedione (ASD), and clinical and laboratory measures of disease activity such as C-reactive protein and IL-6 concentrations at baseline and after 1, 3, 6, 9 and 12 months of glucocorticoid treatment. To assess dynamic HPA axis function, serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels were evaluated in another 8 patients with recent onset PMR not treated with glucocorticoid in comparison to controls after challenge with ovine corticotropin releasing hormone (oCRH) test. In addition, serum cortisol and 17-hydroxyprogesterone (17-OHP) levels were evaluated after stimulation with low dose (1 microg) intravenous ACTH. Serum cortisol and ASD levels of all PMR patients at baseline did not differ from controls. During followup, cortisol levels dipped at one and 3 months. Serum DHEAS levels in all patients were significantly lower than in controls at baseline. In female PMR patients a significant correlation was found at baseline between cortisol levels and duration of disease. Serum concentrations of IL-6 at baseline were significantly higher in PMR patients than in controls. During 12 months of glucocorticoid treatment IL-6 levels dropped significantly at one month; thereafter they remained stable and did not increase again despite tapering of the glucocorticoid dose. After oCRH stimulation, a similar cortisol response was found in patients and controls. After ACTH

  11. Gamma-hydroxybutyrate enhances mood and prosocial behavior without affecting plasma oxytocin and testosterone.

    Science.gov (United States)

    Bosch, Oliver G; Eisenegger, Christoph; Gertsch, Jürg; von Rotz, Robin; Dornbierer, Dario; Gachet, M Salomé; Heinrichs, Markus; Wetter, Thomas C; Seifritz, Erich; Quednow, Boris B

    2015-12-01

    Gamma-hydroxybutyrate (GHB) is a GHB-/GABAB-receptor agonist. Reports from GHB abusers indicate euphoric, prosocial, and empathogenic effects of the drug. We measured the effects of GHB on mood, prosocial behavior, social and non-social cognition and assessed potential underlying neuroendocrine mechanisms. GHB (20mg/kg) was tested in 16 healthy males, using a randomized, placebo-controlled, cross-over design. Subjective effects on mood were assessed by visual-analogue-scales and the GHB-Specific-Questionnaire. Prosocial behavior was examined by the Charity Donation Task, the Social Value Orientation test, and the Reciprocity Task. Reaction time, memory, empathy, and theory-of-mind were also tested. Blood plasma levels of GHB, oxytocin, testosterone, progesterone, dehydroepiandrosterone (DHEA), cortisol, aldosterone, and adrenocorticotropic-hormone (ACTH) were determined. GHB showed stimulating and sedating effects, and elicited euphoria, disinhibition, and enhanced vitality. In participants with low prosociality, the drug increased donations and prosocial money distributions. In contrast, social cognitive abilities such as emotion recognition, empathy, and theory-of-mind, and basal cognitive functions were not affected. GHB increased plasma progesterone, while oxytocin and testosterone, cortisol, aldosterone, DHEA, and ACTH levels remained unaffected. GHB has mood-enhancing and prosocial effects without affecting social hormones such as oxytocin and testosterone. These data suggest a potential involvement of GHB-/GABAB-receptors and progesterone in mood and prosocial behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Oxytocin promotes group-serving dishonesty.

    Science.gov (United States)

    Shalvi, Shaul; De Dreu, Carsten K W

    2014-04-15

    To protect and promote the well-being of others, humans may bend the truth and behave unethically. Here we link such tendencies to oxytocin, a neuropeptide known to promote affiliation and cooperation with others. Using a simple coin-toss prediction task in which participants could dishonestly report their performance levels to benefit their group's outcome, we tested the prediction that oxytocin increases group-serving dishonesty. A double-blind, placebo-controlled experiment allowing individuals to lie privately and anonymously to benefit themselves and fellow group members showed that healthy males (n = 60) receiving intranasal oxytocin, rather than placebo, lied more to benefit their group, and did so faster, yet did not necessarily do so because they expected reciprocal dishonesty from fellow group members. Treatment effects emerged when lying had financial consequences and money could be gained; when losses were at stake, individuals in placebo and oxytocin conditions lied to similar degrees. In a control condition (n = 60) in which dishonesty only benefited participants themselves, but not fellow group members, oxytocin did not influence lying. Together, these findings fit a functional perspective on morality revealing dishonesty to be plastic and rooted in evolved neurobiological circuitries, and align with work showing that oxytocin shifts the decision-maker's focus from self to group interests. These findings highlight the role of bonding and cooperation in shaping dishonesty, providing insight into when and why collaboration turns into corruption.

  13. Ovarian hormones modify anxiety behavior and glucocorticoid receptors after chronic social isolation stress.

    Science.gov (United States)

    Ramos-Ortolaza, Dinah L; Doreste-Mendez, Raura J; Alvarado-Torres, John K; Torres-Reveron, Annelyn

    2017-06-15

    Chronic social isolation could lead to a disruption in the Hypothalamic-Pituitary-Adrenal (HPA) axis, resulting in anxiety and depressive-like behaviors but cycling estrogens could modify these behaviors. The aim of this study was to determine if changes in ovarian hormones during the normal cycle could interact with social isolation to alter anxiety and depressive-like behaviors. In parallel, we examined the expression of glucocorticoid receptor (GR) and synaptic vesicle protein synaptophysin in the hippocampus and hypothalamus of Sprague Dawley normal cycling female rats. We assigned rats to either isolated or paired housing for 8 weeks. To assess anxiety and depressive-like behaviors, we used the open field test and forced swim test, respectively. Female rats were tested at either diestrus, estrus, or proestrus stage of the estrous cycle. After behaviors, rats were perfused and brains collected. Brain sections containing hippocampus and hypothalamus were analyzed using immunohistochemistry for synaptophysin and glucocorticoid receptor (GR) levels. We found an increase in depressive-like behaviors for isolated animals compared to paired housed rats, regardless of the estrous cycle stage. Interestingly, we found a decrease in anxiety behaviors in females in the estrus stage accompanied by a decrease in GR expression in hippocampal DG and CA3. However, no changes in synaptophysin were observed in any of the areas of studied. Our results support the beneficial effects of circulating ovarian hormones in anxiety, possibly by decreasing GR expression. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Multiple sclerosis, relapses, and the mechanism of action of adrenocorticotropic hormone (ACTH

    Directory of Open Access Journals (Sweden)

    Amy ePerrin Ross

    2013-03-01

    Full Text Available Relapses in multiple sclerosis (MS are disruptive and frequently disabling for patients, and their treatment is often a challenge to clinicians. Despite progress in the understanding of the pathophysiology of MS and development of new treatments for long-term management of MS, options for treating relapses have not changed substantially over the past few decades. Corticosteroids, a component of the HPA axis that modulate immune responses and reduce inflammation, are currently the mainstay of relapse treatment. Adrenocorticotropic hormone (ACTH gel is another treatment option. Although it has long been assumed that the efficacy of ACTH in treating relapses depends on the peptide’s ability to increase endogenous corticosteroid production, evidence from research on the melanocortin system suggests that steroidogenesis may only partly account for ACTH influences. Indeed, the melanocortin peptides (ACTH and α-, β-, γ-melanocyte-stimulating hormones [MSH] and their receptors (MCRs exert multiple actions, including modulation of inflammatory and immune mediator production. Melanocortin receptors are widely distributed within the central nervous system and in peripheral tissues including immune cells (eg, macrophages. This suggests that the mechanism of action of ACTH includes not only steroid-mediated indirect effects, but also direct anti-inflammatory and immune-modulating actions via the melanocortin system. An increased understanding of the role of the melanocortin system, particularly ACTH, in the immune and inflammatory processes underlying relapses may help to improve relapse management.

  15. A ghrelin-growth hormone axis drives stress-induced vulnerability to enhanced fear.

    Science.gov (United States)

    Meyer, R M; Burgos-Robles, A; Liu, E; Correia, S S; Goosens, K A

    2014-12-01

    Hormones in the hypothalamus-pituitary-adrenal (HPA) axis mediate many of the bodily responses to stressors, yet there is no clear relationship between the levels of these hormones and stress-associated mental illnesses such as posttraumatic stress disorder (PTSD). Therefore, other hormones are likely to be involved in this effect of stress. Here we used a rodent model of PTSD in which rats repeatedly exposed to a stressor display heightened fear learning following auditory Pavlovian fear conditioning. Our results show that stress-related increases in circulating ghrelin, a peptide hormone, are necessary and sufficient for stress-associated vulnerability to exacerbated fear learning and these actions of ghrelin occur in the amygdala. Importantly, these actions are also independent of the classic HPA stress axis. Repeated systemic administration of a ghrelin receptor agonist enhanced fear memory but did not increase either corticotropin-releasing factor (CRF) or corticosterone. Repeated intraamygdala infusion of a ghrelin receptor agonist produced a similar enhancement of fear memory. Ghrelin receptor antagonism during repeated stress abolished stress-related enhancement of fear memory without blunting stress-induced corticosterone release. We also examined links between ghrelin and growth hormone (GH), a major downstream effector of the ghrelin receptor. GH protein was upregulated in the amygdala following chronic stress, and its release from amygdala neurons was enhanced by ghrelin receptor stimulation. Virus-mediated overexpression of GH in the amygdala was also sufficient to increase fear. Finally, virus-mediated overexpression of a GH receptor antagonist was sufficient to block the fear-enhancing effects of repeated ghrelin receptor stimulation. Thus, ghrelin requires GH in the amygdala to exert fear-enhancing effects. These results suggest that ghrelin mediates a novel branch of the stress response and highlight a previously unrecognized role for ghrelin and

  16. Modelling of the Hypothalamic-Pituitary-Adrenal Axis Perturbations by Externally Induced Cholesterol Pulses of Finite Duration and with Asymmetrically Distributed Concentration Profile

    Science.gov (United States)

    Stanojević, A.; Marković, V. M.; Čupić, Ž.; Vukojević, V.; Kolar-Anić, L.

    2017-12-01

    A model was developed that can be used to study the effect of gradual cholesterol intake by food on the HPA axis dynamics. Namely, well defined oscillatory dynamics of vital neuroendocrine hypothalamic-pituitary-adrenal (HPA) axis has proven to be necessary for maintaining regular basal physiology and formulating appropriate stress response to various types of perturbations. Cholesterol, as a precursor of all steroid HPA axis hormones, can alter the dynamics of HPA axis. To analyse its particular influence on the HPA axis dynamics we used stoichiometric model of HPA axis activity, and simulate cholesterol perturbations in the form of finite duration pulses, with asymmetrically distributed concentration profile. Our numerical simulations showed that there is a complex, nonlinear dependence between the HPA axis responsiveness and different forms of applied cholesterol concentration pulses, indicating the significance of kinetic modelling, and dynamical systems theory for the understanding of large-scale self-regulatory, and homeostatic processes within this neuroendocrine system.

  17. Oxytocin modulates female sociosexual behavior through a specific class of prefrontal cortical interneurons

    Science.gov (United States)

    Nakajima, Miho; Görlich, Andreas; Heintz, Nathaniel

    2014-01-01

    SUMMARY Human imaging studies have revealed that intranasal administration of the “prosocial” hormone oxytocin (OT) activates the frontal cortex, and that this action of OT correlates with enhanced brain function in autism. Here we report the discovery of a population of somatostatin (Sst) positive, regular spiking interneurons that express the oxytocin receptor (OxtrINs). Silencing of OxtrINs in the medial prefrontal cortex (mPFC) of female mice resulted in loss of social interest in male mice specifically during the sexually receptive phase of the estrous cycle. This sociosexual deficit was also present in mice in which the Oxtr gene was conditionally deleted from the mPFC, and in control mice infused with an Oxtr antagonist. Our data demonstrate a gender, cell type and state specific role for OT/Oxtr signaling in the mPFC, and identify a latent cortical circuit element that may modulate other complex social behaviors in response to OT. PMID:25303526

  18. A general approach-avoidance hypothesis of oxytocin: accounting for social and non-social effects of oxytocin.

    Science.gov (United States)

    Harari-Dahan, Osnat; Bernstein, Amit

    2014-11-01

    We critically reexamine extant theory and empirical study of Oxytocin. We question whether OT is, in fact, a "social neuropeptide" as argued in dominant theories of OT. We critically review human and animal research on the social and non-social effects of Oxytocin, including behavioral, psychophysiological, neurobiological, and neuroimaging studies. We find that extant (social) theories of Oxytocin do not account for well-documented non-social effects of Oxytocin. Furthermore, we find a range of evidence that social and non-social effects of Oxytocin may be mediated by core approach-avoidance motivational processes. We propose a General Approach-avoidance Hypothesis of Oxytocin (GAAO). We argue that the GAAO may provide a parsimonious account of established social and non-social effects of Oxytocin. We thus re-conceptualize the basic function(s) and mechanism(s) of action of Oxytocin. Finally, we highlight implications of the GAAO for basic and clinical research in humans

  19. The impact of intranasal oxytocin on attention to social emotional stimuli in patients with anorexia nervosa: a double blind within-subject cross-over experiment.

    Directory of Open Access Journals (Sweden)

    Youl-Ri Kim

    Full Text Available BACKGROUND AND AIM: Social factors may be of importance causally and act as maintenance factors in patients with anorexia nervosa. Oxytocin is a neuromodulatory hormone involved in social emotional processing associated with attentional processes. This study aimed to examine the impact of oxytocin on attentional processes to social faces representing anger, disgust, and happiness in patients with anorexia nervosa. METHOD: A double-blind, placebo-controlled within-subject crossover design was used. Intranasal oxytocin or placebo followed by a visual probe detection task with faces depicting anger, disgust, and happiness was administered to 64 female subjects: 31 patients with anorexia nervosa and 33 control students. RESULTS: Attentional bias to the disgust stimuli was observed in both groups under the placebo condition. The attentional bias to disgust was reduced under the oxytocin condition (a moderate effect in the patient group. Avoidance of angry faces was observed in the patient group under the placebo condition and vigilance was observed in the healthy comparison group; both of these information processing responses were moderated by oxytocin producing an increase in vigilance in the patients. Happy/smiling faces did not elicit an attentional response in controls or the patients under either the placebo or oxytocin conditions. CONCLUSION: Oxytocin attenuated attentional vigilance to disgust in patients with anorexia nervosa and healthy controls. On the other hand, oxytocin changed the response to angry faces from avoidance to vigilance in patients but reduced vigilance to anger in healthy controls. We conclude that patients with anorexia nervosa appear to use different strategies/circuits to emotionally process anger from their healthy counterparts.

  20. Does perinatal exposure to exogenous oxytocin influence child behavioural problems and autistic-like behaviours to 20 years of age?

    Science.gov (United States)

    Guastella, A J; Cooper, M N; White, C R H; White, M K; Pennell, C E; Whitehouse, A J O

    2018-04-27

    The neuropeptide and hormone oxytocin is known to have a significant impact on social cognition and behaviour in humans. There is growing concern regarding the influence of exogenous oxytocin (OT) administration in early life on later social and emotional development, including autism spectrum disorder (ASD). No study has examined offspring development in relation to the dose of exogenous oxytocin administered during labour. Between 1989 and 1992, 2,900 mothers were recruited prior to the 18th week of pregnancy, delivering 2,868 live offspring. The Child Behaviour Checklist was used to measure offspring behavioural difficulties at ages 5, 8, 10, 14 and 17 years. Autism spectrum disorder was formally diagnosed by consensus of a team of specialists. At 20 years, offspring completed a measure of autistic-like traits, the Autism Spectrum Quotient (AQ). Oxytocin exposure prior to birth was analysed using categorical and continuous approaches (maternal oxytocin dose) with univariate and multivariate statistical techniques. Categorical analyses of oxytocin exposure prior to birth demonstrated no group differences in any measures of child behaviour. A small in magnitude dose-response association was observed for clinically significant total behaviour symptoms (adjusted odds ratio 1.03; 95% CI: 1.01-1.06, p Exogenous oxytocin administration prior to birth was not associated with ASD (OR: 0.64; 95% CI: 0.15-2.12, p = .46) or high levels of autistic-like traits (p = .93), as assessed by the AQ. This study is the first to investigate longitudinal mental health outcomes associated with the use of oxytocin-based medications during labour. The results do not provide evidence to support the theory that exogenous OT has a clinically significant negative impact on the long-term mental health of children. © 2018 Association for Child and Adolescent Mental Health.

  1. Plasma cortisol and oxytocin levels predict help-seeking intentions for depressive symptoms.

    Science.gov (United States)

    Thomas, Susan; Larkin, Theresa

    2018-01-01

    Depressed individuals often refuse or withdraw from help, a phenomenon termed help-negation, which is a risk factor for poor outcomes. Most previous research has investigated psychosocial factors including stigma as causes of low help-seeking intentions for depression, however these do not adequately explain the problem. We hypothesised that because help-negation worsens with symptom severity, it might be linked to important biological changes associated with depression itself. We investigated the relative contributions of cortisol, a stress hormone linked to depression, and oxytocin, a hormone which mediates social behaviours, alongside psychosocial factors, to help-seeking intentions among depressed and non-depressed individuals. Morning plasma cortisol and oxytocin levels, psychopathology, suicidal ideation, help-seeking intentions from informal sources including family and friends, and formal sources including health professionals, and perceived social support were quantified in 63 adults meeting DSM-5 criteria for major depressive disorder (MDD) who were not receiving any treatment, and 60 healthy controls. Between-group analyses of variance, correlations, and hierarchical multiple regressions were employed. Help-seeking intentions were lower in depressed than healthy participants, negatively correlated to cortisol and positively correlated to oxytocin. Cortisol negatively, and oxytocin positively, predicted help-seeking intentions from informal but not formal sources, after controlling for psychopathology and psychosocial factors. Neuroendocrine changes associated with depression may contribute to low help-seeking from friends and family, which may have implications for interpersonal support and outcomes. Research and clinical approaches which incorporate biological as well as psychosocial factors may allow for more targeted and effective early interventions to address lack of help-seeking and depression progression. Copyright © 2017 Elsevier Ltd. All rights

  2. Gene expression of estrogen and oxytocin receptors in the uterus of pregnant and parturient bitches

    Energy Technology Data Exchange (ETDEWEB)

    Veiga, G.A.L. [Departamento de Reprodução Animal, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP (Brazil); Milazzotto, M.P. [Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP (Brazil); Nichi, M.; Lúcio, C.F.; Silva, L.C.G.; Angrimani, D.S.R.; Vannucchi, C.I. [Departamento de Reprodução Animal, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP (Brazil)

    2015-02-13

    In the canine species, the precise mechanisms of pregnancy maintenance and the initiation of parturition are not completely understood. The expression of genes encoding the receptors for estrogen (ERα mRNA) and oxytocin (OTR mRNA) was studied in the endometrium and myometrium during pregnancy and parturition in dogs. Real-time PCR was performed to quantify the levels of ERα mRNA and OTR mRNA in the uterus of bitches during early (up to 20 days of gestation), mid (20 to 40 days) and late pregnancy (41 to 60 days), and parturition (first stage of labor). All tissues expressed ERα and OTR mRNA, and are thus possibly able to respond to eventual estrogen and oxytocin hormonal stimuli. No statistically significant differences in the expression of ERα mRNA were verified in the endometrium and myometrium throughout pregnancy and parturition, but expression of OTR mRNA increased at both parturition and late pregnancy. We concluded that the increase of endometrial and myometrial OTR mRNA expression in dogs is not an event dependent on estrogenic stimulation. Moreover, the contractility response of the canine uterus to oxytocin begins during pregnancy and maintains myometrial activity. The expression of OTR mRNA in canine uterine tissues varied over time, which supports an interpretation that the sensitivity and response to hormone therapy varies during the course of pregnancy and labor. Further studies are needed to elucidate the factors underlying the synthesis of uterine oxytocin receptors and the possible role of ERβ rather than ERα in the uterine tissues during pregnancy and parturition in dogs.

  3. Gene expression of estrogen and oxytocin receptors in the uterus of pregnant and parturient bitches

    International Nuclear Information System (INIS)

    Veiga, G.A.L.; Milazzotto, M.P.; Nichi, M.; Lúcio, C.F.; Silva, L.C.G.; Angrimani, D.S.R.; Vannucchi, C.I.

    2015-01-01

    In the canine species, the precise mechanisms of pregnancy maintenance and the initiation of parturition are not completely understood. The expression of genes encoding the receptors for estrogen (ERα mRNA) and oxytocin (OTR mRNA) was studied in the endometrium and myometrium during pregnancy and parturition in dogs. Real-time PCR was performed to quantify the levels of ERα mRNA and OTR mRNA in the uterus of bitches during early (up to 20 days of gestation), mid (20 to 40 days) and late pregnancy (41 to 60 days), and parturition (first stage of labor). All tissues expressed ERα and OTR mRNA, and are thus possibly able to respond to eventual estrogen and oxytocin hormonal stimuli. No statistically significant differences in the expression of ERα mRNA were verified in the endometrium and myometrium throughout pregnancy and parturition, but expression of OTR mRNA increased at both parturition and late pregnancy. We concluded that the increase of endometrial and myometrial OTR mRNA expression in dogs is not an event dependent on estrogenic stimulation. Moreover, the contractility response of the canine uterus to oxytocin begins during pregnancy and maintains myometrial activity. The expression of OTR mRNA in canine uterine tissues varied over time, which supports an interpretation that the sensitivity and response to hormone therapy varies during the course of pregnancy and labor. Further studies are needed to elucidate the factors underlying the synthesis of uterine oxytocin receptors and the possible role of ERβ rather than ERα in the uterine tissues during pregnancy and parturition in dogs

  4. Gene expression of estrogen and oxytocin receptors in the uterus of pregnant and parturient bitches.

    Science.gov (United States)

    Veiga, G A L; Milazzotto, M P; Nichi, M; Lúcio, C F; Silva, L C G; Angrimani, D S R; Vannucchi, C I

    2015-04-01

    In the canine species, the precise mechanisms of pregnancy maintenance and the initiation of parturition are not completely understood. The expression of genes encoding the receptors for estrogen (ERα mRNA) and oxytocin (OTR mRNA) was studied in the endometrium and myometrium during pregnancy and parturition in dogs. Real-time PCR was performed to quantify the levels of ERα mRNA and OTR mRNA in the uterus of bitches during early (up to 20 days of gestation), mid (20 to 40 days) and late pregnancy (41 to 60 days), and parturition (first stage of labor). All tissues expressed ERα and OTR mRNA, and are thus possibly able to respond to eventual estrogen and oxytocin hormonal stimuli. No statistically significant differences in the expression of ERα mRNA were verified in the endometrium and myometrium throughout pregnancy and parturition, but expression of OTR mRNA increased at both parturition and late pregnancy. We concluded that the increase of endometrial and myometrial OTR mRNA expression in dogs is not an event dependent on estrogenic stimulation. Moreover, the contractility response of the canine uterus to oxytocin begins during pregnancy and maintains myometrial activity. The expression of OTR mRNA in canine uterine tissues varied over time, which supports an interpretation that the sensitivity and response to hormone therapy varies during the course of pregnancy and labor. Further studies are needed to elucidate the factors underlying the synthesis of uterine oxytocin receptors and the possible role of ERβ rather than ERα in the uterine tissues during pregnancy and parturition in dogs.

  5. Determination of plasma oxytocin by radioimmunoassay

    International Nuclear Information System (INIS)

    Ogawa, Satsuki; Fukuchi, Soitsu; Miura, Tadashi

    1978-01-01

    A simple radioimmunoassay was applied to the measurement of oxytocin in human plasma. A high specificity of immunoassay was demonstrated by the fact that large excess of angiotensin I and II, and ACTH did not displace labelled oxytocin from the antibody. Lysine-8-vasopressin and arginine-8-vasopressin showed very little cross-reaction in the assay, possessing only 0.002% of the immunological potency of oxytocin. The specific activity of 125 I-oxytocin was 166 μCi/μg. Adsorption and extraction capacities of Florisil were 96.6 +- 2.1% and 85.7 +- 2.5%, respectively. Intra- and inter-assay variability were 7.2 +- 4.9% and 4.3 +- 2.2%, respectively. The sensitivity of the assay was below 1 pg/tube. Normal levels of plasma oxytocin were 0 - 2.2 pg/ml (n=13) in males and 0 - 10.4 pg/ml (n=10) in females. Plasma oxytocin levels in the 39th and 40th weeks of pregnancy were 27.9 +- 4.14 pg/ml (n=4) and 29.8 +- 17.1 pg/ml (n=13), respectively. The levels increased to 33.1 +- 12.1 pg/ml (n=7) and 37.1 +- 17.5 pg/ml (n=7) in the first and third stages of labor, and decreased to 13.6 +- 5.25 pg/ml (n=6) on the 2nd to 8th day after labor. The radioimmunoassay for oxytocin in plasma is considered to be sufficiently applicable for clinical use. (auth.)

  6. Impact of opioid therapy on gonadal hormones: focus on buprenorphine.

    Science.gov (United States)

    Varma, Anjali; Sapra, Mamta; Iranmanesh, Ali

    2018-02-17

    Objective The USA is in the midst of an opioid crisis. Understanding the impact of opioids and commonly used treatments for opioid dependence is essential for clinicians and researchers in order to educate and treat the nation's growing population with opioid use disorders. As a relatively new treatment for opioid dependence, buprenorphine is gaining popularity to the extent of becoming not only a preferred approach to the maintenance of opiate addiction, but also an option for chronic pain management. The purpose of this report is to review the available evidence on the endocrine effects of buprenorphine, particularly as it relates to the hypothalamic-pituitary-gonadal (HPG) axis, which is controversial and not fully defined. Method We conducted a Pubmed search (2000-2017) for human studies in the English language for articles that were available as full length regarding buprenorphine, endocrinopathy, hypogonadism, bone density, opioids. Case reports were also reviewed, although prospective studies and randomized controlled trials received more weight. Results Opioid induced hypogonadism is well established. Most studies report that buprenorphine being a partial agonist/antagonist may not be impacting the pituitary trophic hormones as much. There are reports of sexual dysfunction in subjects maintained on buprenorphine, some without hormonal correlation. Thus with the understanding that pertinent clinical studies are limited in number, varied in methodology, mostly cross sectional, predominantly in men and small number of participants, more research in this area is warranted. Conclusion Based on a comprehensive review of the available literature, we conclude that despite its increasing popularity, buprenorphine has not been adequately studied in respect to its long-term effects on the hypothalamic-pituitary-adrenal (HPA) axis. There is a great need for longitudinal systematic trials to define the potential buprenorphine-induced endocrine consequences.

  7. A randomised controlled trial comparing oxytocin and oxytocin + ergometrine for prevention of postpartum haemorrhage at caesarean section.

    Science.gov (United States)

    Koen, Sandy; Snyman, Leon Cornelius; Pattinson, Robert C; Makin, Jennifer A

    2016-03-07

    Globally 166 000 women die annually as a result of obstetric haemorrhage. More than 50% of these deaths occur in sub-Saharan Africa. Uterine atony is the commonest cause of severe postpartum haemorrhage (PPH). Bleeding at or after caesarean section (CS) is responsible for >30% of maternal deaths due to obstetric haemorrhage in South Africa (SA). To compare oxytocin alone with oxytocin + ergometrine in terms of primary prophylaxis for PPH at the time of CS. This was a double-blind randomised controlled interventional study comparing oxytocin with oxytocin + ergometrine administered during CS. Patients were randomised to receive oxytocin alone intravenously as a bolus or oxytocin + ergometrine intramuscularly, with the placebo being an injection of sterile water. The study population consisted of women undergoing CS at Kalafong Provincial Tertiary Hospital in Atteridgeville, Gauteng, SA. Five hundred and forty women were randomised and data for 416 women, of whom 214 received oxytocin and 202 oxytocin + ergometrine, were available for analysis. In the oxytocin group 19 women (8.9%) required blood transfusion, compared with seven (3.5%) in the oxytocin + ergometrine group (p=0.01; relative risk = 2.78; 95% confidence interval 1.21 - 6.4). There were no statistically significant differences in the mean estimated visual and mean calculated blood loss. The overall need for blood transfusion was significantly reduced by about two-thirds in women receiving the oxytocin + ergometrine combination. Consideration should be given to using oxytocin + ergometrine for prophylaxis of PPH at CS.

  8. Fto colocalizes with a satiety mediator oxytocin in the brain and upregulates oxytocin gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Olszewski, Pawel K., E-mail: olsze005@umn.edu [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Minnesota Obesity Center, Saint Paul, MN 55108 (United States); Fredriksson, Robert; Eriksson, Jenny D. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Mitra, Anaya [Department of Food Science and Nutrition, Saint Paul, MN 55108 (United States); Radomska, Katarzyna J. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Gosnell, Blake A. [Department of Food Science and Nutrition, Saint Paul, MN 55108 (United States); Solvang, Maria N. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden); Levine, Allen S. [Minnesota Obesity Center, Saint Paul, MN 55108 (United States); Department of Food Science and Nutrition, Saint Paul, MN 55108 (United States); Schioeth, Helgi B. [Department of Neuroscience, Functional Pharmacology, Uppsala University, 75124 Uppsala (Sweden)

    2011-05-13

    Highlights: {yields} The majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto. {yields} The level of colocalization is similar in the male and female brain. {yields} Fto overexpression in hypothalamic neurons increases oxytocin mRNA levels by 50%. {yields} Oxytocin does not affect Fto expression through negative feedback mechanisms. -- Abstract: Single nucleotide polymorphisms in the fat mass and obesity-associated (FTO) gene have been associated with obesity in humans. Alterations in Fto expression in transgenic animals affect body weight, energy expenditure and food intake. Fto, a nuclear protein and proposed transcription co-factor, has been speculated to affect energy balance through a functional relationship with specific genes encoding feeding-related peptides. Herein, we employed double immunohistochemistry and showed that the majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto in the brain of male and female mice. We then overexpressed Fto in a murine hypothalamic cell line and, using qPCR, detected a 50% increase in the level of oxytocin mRNA. Expression levels of several other feeding-related genes, including neuropeptide Y (NPY) and Agouti-related protein (AgRP), were unaffected by the FTO transfection. Addition of 10 and 100 nmol oxytocin to the cell culture medium did not affect Fto expression in hypothalamic cells. We conclude that Fto, a proposed transcription co-factor, influences expression of the gene encoding a satiety mediator, oxytocin.

  9. Fto colocalizes with a satiety mediator oxytocin in the brain and upregulates oxytocin gene expression

    International Nuclear Information System (INIS)

    Olszewski, Pawel K.; Fredriksson, Robert; Eriksson, Jenny D.; Mitra, Anaya; Radomska, Katarzyna J.; Gosnell, Blake A.; Solvang, Maria N.; Levine, Allen S.; Schioeth, Helgi B.

    2011-01-01

    Highlights: → The majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto. → The level of colocalization is similar in the male and female brain. → Fto overexpression in hypothalamic neurons increases oxytocin mRNA levels by 50%. → Oxytocin does not affect Fto expression through negative feedback mechanisms. -- Abstract: Single nucleotide polymorphisms in the fat mass and obesity-associated (FTO) gene have been associated with obesity in humans. Alterations in Fto expression in transgenic animals affect body weight, energy expenditure and food intake. Fto, a nuclear protein and proposed transcription co-factor, has been speculated to affect energy balance through a functional relationship with specific genes encoding feeding-related peptides. Herein, we employed double immunohistochemistry and showed that the majority of neurons synthesizing a satiety mediator, oxytocin, coexpress Fto in the brain of male and female mice. We then overexpressed Fto in a murine hypothalamic cell line and, using qPCR, detected a 50% increase in the level of oxytocin mRNA. Expression levels of several other feeding-related genes, including neuropeptide Y (NPY) and Agouti-related protein (AgRP), were unaffected by the FTO transfection. Addition of 10 and 100 nmol oxytocin to the cell culture medium did not affect Fto expression in hypothalamic cells. We conclude that Fto, a proposed transcription co-factor, influences expression of the gene encoding a satiety mediator, oxytocin.

  10. Oxytocin attenuates social and non-social avoidance: Re-thinking the social specificity of Oxytocin.

    Science.gov (United States)

    Harari-Dahan, Osnat; Bernstein, Amit

    2017-07-01

    Re-examining decades of the social construal of Oxytocin, the General Approach-Avoidance Hypothesis of Oxytocin (GAAO) predicts that Oxytocin will modulate responding to emotionally-evocative and personally-relevant social and non-social stimuli due to its action on the neural substrate of approach and avoidance motivation. We report the first critical experimental test of GAAO predictions by means of a double-blind intra-nasal administration of Oxytocin vs. placebo in 90 healthy adults (N=90, 50% women). As predicted, we found that among men and women for whom negative emotion (anxious arousal) is motivationally-relevant, intra-nasal administration of Oxytocin reduced behavioral avoidance of emotionally-evocative negatively-valenced social and non-social stimuli, but not closely matched emotionally-neutral stimuli. Findings cannot be explained by extant social theories of Oxytocin. We discuss the implications of the present findings for basic and translational clinical Oxytocin research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Oxytocin, Motivation and the Role of Dopamine

    Science.gov (United States)

    Love, Tiffany M.

    2013-01-01

    The hypothalamic neuropeptide oxytocin has drawn the attention of scientists for more than a century. The understanding of the function of oxytocin has expanded dramatically over the years from a simple peptide adept at inducing uterine contractions and milk ejection to a complex neuromodulator with a capacity to shape human social behavior. Decades of research have outlined oxytocin’s ability to enhance intricate social activities ranging from pair bonding, sexual activity, affiliative preferences, and parental behaviors. The precise neural mechanisms underlying oxytocin’s influence on such behaviors have just begun to be understood. Research suggests that oxytocin interacts closely with the neural pathways responsible for processing motivationally relevant stimuli. In particular, oxytocin appears to impact dopaminergic activity within the mesocorticolimbic dopamine system, which is crucial not only for reward and motivated behavior but also for the expression of affiliative behaviors. Though most of the work performed in this area has been done using animal models, several neuroimaging studies suggest similar relationships may be observed in humans. In order to introduce this topic further, this paper will review the recent evidence that oxytocin may exert some of its social-behavioral effects through its impact on motivational networks. PMID:23850525

  12. Sex-Specific Effects of Stress on Oxytocin Neurons Correspond With Responses to Intranasal Oxytocin.

    Science.gov (United States)

    Steinman, Michael Q; Duque-Wilckens, Natalia; Greenberg, Gian D; Hao, Rebecca; Campi, Katharine L; Laredo, Sarah A; Laman-Maharg, Abigail; Manning, Claire E; Doig, Ian E; Lopez, Eduardo M; Walch, Keenan; Bales, Karen L; Trainor, Brian C

    2016-09-01

    Oxytocin (OT) is considered to be a stress-buffering hormone, dampening the physiologic effects of stress. However, OT can also be anxiogenic. We examined acute and long-lasting effects of social defeat on OT neurons in male and female California mice. We used immunohistochemistry for OT and c-fos cells to examine OT neuron activity immediately after defeat (n = 6-9) and 2 weeks (n = 6-9) and 10 weeks (n = 4-5) later. We quantified Oxt messenger RNA with quantitative polymerase chain reaction (n = 5-9). Intranasal OT was administered to naïve and stressed mice tested in social interaction and resident-intruder tests (n = 8-14). Acute exposure to a third episode of defeat increased OT/c-fos colocalizations in the paraventricular nucleus of both sexes. In the medioventral bed nucleus of the stria terminalis, defeat increased Oxt messenger RNA, total OT neurons, and OT/c-fos colocalizations in female mice but not male mice. Intranasal OT failed to reverse stress-induced social withdrawal in female mice and reduced social interaction behavior in female mice naïve to defeat. In contrast, intranasal OT increased social interaction in stressed male mice and reduced freezing in the resident-intruder test. Social defeat induces long-lasting increases in OT production and OT/c-fos cells in the medioventral bed nucleus of the stria terminalis of female mice but not male mice. Intranasal OT largely reversed the effects of stress on behavior in male mice, but effects were mixed in female mice. These results suggest that changes in OT-sensitive networks contribute to sex differences in behavioral responses to stress. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  13. Glucocorticoids and relapse of major depression (dexamethasone/corticotropin-releasing hormone test in relation to relapse of major depression)

    NARCIS (Netherlands)

    Appelhof, Bente C.; Huyser, Jochanan; Verweij, Mijke; Brouwer, Jantien P.; van Dyck, Richard; Fliers, Eric; Hoogendijk, Witte J. G.; Tijssen, Jan G. P.; Wiersinga, Wilmar M.; Schene, Aart H.

    2006-01-01

    BACKGROUND: Knowledge of pathogenic mechanisms and predictors of relapse in major depressive disorder is still limited. Hypothalamic-pituitary-adrenocortical (HPA) axis dysregulation is thought to be related to the development and course of depression. METHODS: We investigated whether

  14. Human ovolution and plasma oxytocin

    International Nuclear Information System (INIS)

    Kumaresan, Perianna; Kumaresan, Malathi; Hossini, Mahmood; Arellano, Carolina; Vasicka, Alois

    1983-01-01

    Plasma oxytocin (OT) concentrations were measured by radioimmunoassay (RIA) method without extracting plasma in 11 normal menstruating women. Mean plasma OT level began to increase steadily from the 7th day of the menstrual cycle and this level rose up to 20+-5 μU/ml (Mean+-S.E.) on the 10th day of the cycle. OT level declined to 13+-6 μU/ml on the day of the LH peak and continuously declined for another 2 days - then rose. The OT level was higher during the follicular phase than during the luteal phase. In 1 individual OT measured in 2 cycles a year apart showed the highest level of OT coincided with LH and FSH peak and abruptly declined. When there was the highest level of progesterone, the OT level was measurable 1 out of 11 cycles. From this study, we conclude that OT may have a role in human ovulation either synergistically or alone with other ovulatory mechanisms and ovarian estradiol and progesterone control the secretion of OT and also suggests that OT may play some role in the regulation of the luteolysis and the menstrual cycle in women. (author)

  15. Nasally-Administered Oxytocin Has Limited Effects on Owner-Directed Attachment Behavior in Pet Dogs (Canis lupus familiaris).

    Science.gov (United States)

    Thielke, Lauren E; Rosenlicht, Giovanna; Saturn, Sarina R; Udell, Monique A R

    2017-01-01

    The present study explored the effects of intranasal oxytocin, a naturally occurring hormone, on the behavior of pet dogs during an attachment test. Each dog participated in two testing sessions. On one visit saline was administered nasally, and on another, oxytocin was administered nasally. For half of the dogs ( n = 20), solutions were administered with a Mucosal Atomization Device (MAD) and for half of the dogs ( n = 20), solutions were administered using a nasal spray bottle. Condition order was counterbalanced and a double-blind methodology was employed. Following a 30-min wait period after administration of solutions, dog-owner pairs participated in the Secure Base Test, a short attachment test consisting of three 2-min phases: (1) Baseline- the owner was present, dogs were able to freely explore the testing room (2) Alone- dogs were left alone in the testing room (3) Return- owners re-entered the room and were reunited with their dog. In each phase the dog was evaluated for contact seeking, exploration, and avoidance behaviors. Although, oxytocin administration was expected to increase owner-directed proximity and contact seeking behavior, this effect was not observed. In fact, in the baseline phase, dogs spent significantly more time seeking the proximity of their owners when they received saline than when they received OT ( p females spent significantly more time in contact with the door than males in the alone phase ( p oxytocin on attachment related behavior appeared to be limited or inconsistent for this pet dog population.

  16. Adrenal hormones in rats before and after stress-experience: effects of ipsapirone.

    Science.gov (United States)

    Korte, S M; Bouws, G A; Bohus, B

    1992-06-01

    The present study was designed to investigate the effects of the anxiolytic 5-HT1A receptor agonist ipsapirone on the hormonal responses in rats under nonstress and stress conditions by means of repeated blood sampling through an intracardiac catheter. Ipsapirone was given in doses of 2.5, 5, 10, and 20 mg/kg (IP) under nonstress conditions in the home cages of the rats. Plasma corticosterone levels increased in a dose-dependent way in the dose range of 5 to 20 mg/kg, whereas the plasma catecholamines were only significantly increased with the highest dose of the drug. The effect of ipsapirone in control and in stressed rats was studied with the selected dose of 5 mg/kg. Conditioned fear of inescapable electric footshock (0.6 mA, AC for 3 s) given one day earlier was used as stressor. Surprisingly, ipsapirone potentiated the magnitude of the neuroendocrine responses. Rats receiving an inescapable footshock 1 day earlier showed a further elevated corticosterone response to the 5-HT1A receptor agonist ipsapirone even before exposing them to the conditioned stress situation. The present findings suggest that if an animal has no possibilities to escape or avoid a noxious event, functional hypersensitivity will develop in the serotonergic neuronal system, which is reflected in the increased responsiveness of the HPA axis to a 5-HT1A agonist challenge.

  17. Dual-hormone stress reactivity predicts downstream war-zone stress-evoked PTSD.

    Science.gov (United States)

    Josephs, Robert A; Cobb, Adam R; Lancaster, Cynthia L; Lee, Han-Joo; Telch, Michael J

    2017-04-01

    The crucial role of the hypothalamic-pituitary-adrenal axis (HPA) in stress-related homeostasis suggests dysregulated HPA involvement in the pathogenesis of post-traumatic stress disorder (PTSD), yet most studies examining linkages between HPA axis measures and PTSD have yielded null findings. One untested explanation for this inconsistency is a failure to account for simultaneous adrenal and gonadal influence. Here we tested the singular and interactive effects of cortisol (C R ) and testosterone (T R ) reactivity as moderators of war-zone stress evoked PTSD emergence in the war-zone. U.S. soldiers (N=120) scheduled for deployment to Iraq completed pre-deployment measures of C R and T R stress reactivity to a CO 2 inhalation challenge. Once deployed, monthly assessments of exposure to traumatic war-zone stressors and PTSD symptoms were collected via a web-based assessment system. Cortisol hypo-reactivity potentiated the pathogenic impact of war-zone stressors only in soldiers for whom the CO 2 challenge did not elevate testosterone, suggesting that the dual hormone stress reactivity profile of blunted cortisol and testosterone may confer increased risk for PTSD emergence by potentiating the pathogenic effects of war-zone stressors. Findings underscore the utility of assessing both HPA and HPG stress reactivity when assessing PTSD vulnerability and may help inform efforts for enhanced soldier screening and inoculation to war-zone stressors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Associations between complex OHC mixtures and thyroid and cortisol hormone levels in East Greenland polar bears.

    Science.gov (United States)

    Bechshøft, T Ø; Sonne, C; Dietz, R; Born, E W; Muir, D C G; Letcher, R J; Novak, M A; Henchey, E; Meyer, J S; Jenssen, B M; Villanger, G D

    2012-07-01

    The multivariate relationship between hair cortisol, whole blood thyroid hormones, and the complex mixtures of organohalogen contaminant (OHC) levels measured in subcutaneous adipose of 23 East Greenland polar bears (eight males and 15 females, all sampled between the years 1999 and 2001) was analyzed using projection to latent structure (PLS) regression modeling. In the resulting PLS model, most important variables with a negative influence on cortisol levels were particularly BDE-99, but also CB-180, -201, BDE-153, and CB-170/190. The most important variables with a positive influence on cortisol were CB-66/95, α-HCH, TT3, as well as heptachlor epoxide, dieldrin, BDE-47, p,p'-DDD. Although statistical modeling does not necessarily fully explain biological cause-effect relationships, relationships indicate that (1) the hypothalamic-pituitary-adrenal (HPA) axis in East Greenland polar bears is likely to be affected by OHC-contaminants and (2) the association between OHCs and cortisol may be linked with the hypothalamus-pituitary-thyroid (HPT) axis. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Oxytocin modulates hemodynamic responses to monetary incentives in humans.

    Science.gov (United States)

    Mickey, Brian J; Heffernan, Joseph; Heisel, Curtis; Peciña, Marta; Hsu, David T; Zubieta, Jon-Kar; Love, Tiffany M

    2016-12-01

    Oxytocin is a neuropeptide widely recognized for its role in regulating social and reproductive behavior. Increasing evidence from animal models suggests that oxytocin also modulates reward circuitry in non-social contexts, but evidence in humans is lacking. We examined the effects of oxytocin administration on reward circuit function in 18 healthy men as they performed a monetary incentive task. The blood oxygenation level-dependent (BOLD) signal was measured using functional magnetic resonance imaging in the context of a randomized, double-blind, placebo-controlled, crossover trial of intranasal oxytocin. We found that oxytocin increases the BOLD signal in the midbrain (substantia nigra and ventral tegmental area) during the late phase of the hemodynamic response to incentive stimuli. Oxytocin's effects on midbrain responses correlated positively with its effects on positive emotional state. We did not detect an effect of oxytocin on responses in the nucleus accumbens. Whole-brain analyses revealed that oxytocin attenuated medial prefrontal cortical deactivation specifically during anticipation of loss. Our findings demonstrate that intranasal administration of oxytocin modulates human midbrain and medial prefrontal function during motivated behavior. These findings suggest that endogenous oxytocin is a neurochemical mediator of reward behaviors in humans-even in a non-social context-and that the oxytocinergic system is a potential target of pharmacotherapy for psychiatric disorders that involve dysfunction of reward circuitry.

  20. Plasma oxytocin and personality traits in psychiatric outpatients.

    Science.gov (United States)

    Bendix, Marie; Uvnäs-Moberg, Kerstin; Petersson, Maria; Gustavsson, Petter; Svanborg, Pär; Åsberg, Marie; Jokinen, Jussi

    2015-07-01

    The oxytocin system is regarded as being of relevance for social interaction. In spite of this, very few studies have investigated the relationship between oxytocin and personality traits in clinical psychiatric populations. We assessed the relationship between personality traits and plasma oxytocin levels in a population of 101 medication-free psychiatric outpatients (men = 37, women = 64). We used the Karolinska Scale of Personality (KSP) and diagnostic and symptomatic testing. Plasma oxytocin levels were analysed with a specific radioimmunoassay at inclusion and after one month for testing of stability. Plasma oxytocin levels were stable over time and did not differ between patients with or without personality disorders, nor were they related to severity of depressive or anxiety symptoms. The KSP factors Impulsiveness and Negative Emotionality were significant independent predictors of plasma oxytocin. A subscale analysis of these personality factors showed significant positive correlations between baseline plasma oxytocin and the KSP subscales monotony avoidance and psychic anxiety. The significant association between the KSP factor Impulsiveness and oxytocin levels observed at baseline was observed also one month later in men. These findings suggest that personality traits such as Impulsiveness and Negative emotionality which are linked to social functioning in several psychiatric disorders seem to be associated with endogenous plasma oxytocin levels. These variations in oxytocin levels might have an impact on social sensitivity or social motivation with possible gender differences. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Sniffing and Oxytocin: Effects on Olfactory Memories.

    Science.gov (United States)

    Stoop, Ron

    2016-05-04

    In this issue of Neuron, Oettl et al. (2016) show how oxytocin can boost processing of olfactory information in female rats by a top-downregulation from the anterior olfactory nucleus onto the main olfactory bulb. As a result, interactions with juvenile conspecifics receive more attention and are longer memorized. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Labor Augmentation with Oxytocin Decreases Glutathione Level

    Directory of Open Access Journals (Sweden)

    Naomi Schneid-Kofman

    2009-01-01

    Full Text Available Objective. To compare oxidative stress following spontaneous vaginal delivery with that induced by Oxytocin augmented delivery. Methods. 98 women recruited prior to labor. 57 delivered spontaneously, while 41 received Oxytocin for augmentation of labor. Complicated deliveries and high-risk pregnancies were excluded. Informed consent was documented. Arterial cord blood gases, levels of Hematocrit, Hemoglobin, and Bilirubin were studied. Glutathione (GSH concentration was measured by a spectroscopic method. Plasma and red blood cell (RBC levels of Malondialdehyde indicated lipid peroxidation. RBC uptake of phenol red denoted cell penetrability. SPSS data analysis was used. Results. Cord blood GSH was significantly lower in the Oxytocin group (2.3±0.55 mM versus 2.55±0.55 mM, =.01. No differences were found in plasma or RBC levels of MDA or in uptake of Phenol red between the groups. Conclusion. Lower GSH levels following Oxytocin augmentation indicate an oxidative stress, though selected measures of oxidative stress demonstrate no cell damage.

  3. Postnatal depression, oxytocin and maternal sensitivity

    NARCIS (Netherlands)

    Mah, Beth Lynette

    2015-01-01

    Intra nasal oxytocin administered to a population of mothers with a diagnosis of postnatal depression: -lowers their current mood -causes mothers to report that their infants are more difficult but their relationship with them is more positive -increases their protective response towards them in the

  4. Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium.

    Directory of Open Access Journals (Sweden)

    Katarina Lagergren

    Full Text Available The strong male predominance in oesophageal adenocarcinoma (OAC and Barrett's oesophagus (BO continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute.This genetic-epidemiological study pooled 14 studies from three continents, Australia, Europe, and North America. Polymorphisms in 3 key genes coding for the oestrogen pathway (receptor alpha (ESR1, receptor beta (ESR2, and aromatase (CYP19A1, and 3 key genes of the oxytocin pathway (the oxytocin receptor (OXTR, oxytocin protein (OXT, and cyclic ADP ribose hydrolase glycoprotein (CD38, were analysed using a gene-based approach, versatile gene-based test association study (VEGAS.Among 1508 OAC patients, 2383 BO patients, and 2170 controls, genetic variants within ESR1 were associated with BO in males (p = 0.0058 and an increased risk of OAC and BO combined in males (p = 0.0023. Genetic variants within OXTR were associated with an increased risk of BO in both sexes combined (p = 0.0035 and in males (p = 0.0012. We followed up these suggestive findings in a further smaller data set, but found no replication. There were no significant associations between the other 4 genes studied and risk of OAC, BO, separately on in combination, in males and females combined or in males only.Genetic variants in the oestrogen receptor alpha and the oxytocin receptor may be associated with an increased risk of BO or OAC, but replication in other large samples are needed.

  5. Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium.

    Science.gov (United States)

    Lagergren, Katarina; Ek, Weronica E; Levine, David; Chow, Wong-Ho; Bernstein, Leslie; Casson, Alan G; Risch, Harvey A; Shaheen, Nicholas J; Bird, Nigel C; Reid, Brian J; Corley, Douglas A; Hardie, Laura J; Wu, Anna H; Fitzgerald, Rebecca C; Pharoah, Paul; Caldas, Carlos; Romero, Yvonne; Vaughan, Thomas L; MacGregor, Stuart; Whiteman, David; Westberg, Lars; Nyren, Olof; Lagergren, Jesper

    2015-01-01

    The strong male predominance in oesophageal adenocarcinoma (OAC) and Barrett's oesophagus (BO) continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute. This genetic-epidemiological study pooled 14 studies from three continents, Australia, Europe, and North America. Polymorphisms in 3 key genes coding for the oestrogen pathway (receptor alpha (ESR1), receptor beta (ESR2), and aromatase (CYP19A1)), and 3 key genes of the oxytocin pathway (the oxytocin receptor (OXTR), oxytocin protein (OXT), and cyclic ADP ribose hydrolase glycoprotein (CD38)), were analysed using a gene-based approach, versatile gene-based test association study (VEGAS). Among 1508 OAC patients, 2383 BO patients, and 2170 controls, genetic variants within ESR1 were associated with BO in males (p = 0.0058) and an increased risk of OAC and BO combined in males (p = 0.0023). Genetic variants within OXTR were associated with an increased risk of BO in both sexes combined (p = 0.0035) and in males (p = 0.0012). We followed up these suggestive findings in a further smaller data set, but found no replication. There were no significant associations between the other 4 genes studied and risk of OAC, BO, separately on in combination, in males and females combined or in males only. Genetic variants in the oestrogen receptor alpha and the oxytocin receptor may be associated with an increased risk of BO or OAC, but replication in other large samples are needed.

  6. Oxytocin mediated behavior in invertebrates: An evolutionary perspective.

    Science.gov (United States)

    Lockard, Meghan A; Ebert, Margaret S; Bargmann, Cornelia I

    2017-02-01

    The molecular and functional conservation of oxytocin-related neuropeptides in behavior is striking. In animals separated by at least 600 million years of evolution, from roundworms to humans, oxytocin homologs play critical roles in the modulation of reproductive behavior and other biological functions. Here, we review the roles of oxytocin in invertebrate behavior from an evolutionary perspective. We begin by tracing the evolution of oxytocin through the invertebrate animal lineages, and then describe common themes in invertebrate behaviors that are mediated by oxytocin-related peptides, including reproductive behavior, learning and memory, food arousal, and predator/prey relationships. Finally, we discuss interesting future directions that have recently become experimentally tractable. Studying oxytocin in invertebrates offers precise insights into the activity of neuropeptides on well-defined neural circuits; the principles that emerge may also be represented in the more complex vertebrate brain. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 128-142, 2017. © 2016 Wiley Periodicals, Inc.

  7. Sex differences in methamphetamine seeking in rats: Impact of oxytocin

    OpenAIRE

    Cox, Brittney M.; Young, Amy B.; See, Ronald E.; Reichel, Carmela M.

    2013-01-01

    Previous evidence in an animal model of drug self-administration and drug seeking showed that acute oxytocin decreased methamphetamine (meth) seeking in male rats, suggesting potential clinical efficacy for the treatment of psychostimulant addiction. However, based on the well-established role of oxytocin in reproduction and pair bond formation, it is important to know how this effect extrapolates to females. Here, we tested whether oxytocin (1 mg/kg, IP) would decrease meth seeking in female...

  8. Oxytocin and the neural mechanisms regulating social cognition and affiliative behavior.

    Science.gov (United States)

    Ross, Heather E; Young, Larry J

    2009-10-01

    Oxytocin is produced in the hypothalamus and released into the circulation through the neurohypophyseal system. Peripherally released oxytocin facilitates parturition and milk ejection during nursing. Centrally released oxytocin coordinates the onset of maternal nurturing behavior at parturition and plays a role in mother-infant bonding. More recent studies have revealed a more general role for oxytocin in modulating affiliative behavior in both sexes. Oxytocin regulates alloparental care and pair bonding in female monogamous prairie voles. Social recognition in male and female mice is also modulated by oxytocin. In humans, oxytocin increases gaze to the eye region of human faces and enhances interpersonal trust and the ability to infer the emotions of others from facial cues. While the neurohypopheseal oxytocin system has been well characterized, less is known regarding the nature of oxytocin release within the brain. Here we review the role of oxytocin in the regulation of prosocial interactions, and discuss the neuroanatomy of the central oxytocin system.

  9. Oxytocin modulates hemodynamic responses to monetary incentives in humans

    Science.gov (United States)

    Mickey, Brian J.; Heffernan, Joseph; Heisel, Curtis; Peciña, Marta; Hsu, David T.; Zubieta, Jon-Kar; Love, Tiffany M.

    2016-01-01

    Oxytocin is a neuropeptide widely recognized for its role in regulating social and reproductive behavior. Increasing evidence from animal models suggests that oxytocin also modulates reward circuitry in non-social contexts, but evidence in humans is lacking. Here we examined the effects of oxytocin administration on reward circuit function in 18 healthy men as they performed a monetary incentive task. The blood oxygenation level dependent (BOLD) signal was measured using functional magnetic resonance imaging in the context of a randomized, double-blind, placebo-controlled, crossover trial of intranasal oxytocin. We found that oxytocin increases the BOLD signal in the midbrain (substantia nigra and ventral tegmental area) during the late phase of the hemodynamic response to incentive stimuli. Oxytocin’s effects on midbrain responses correlated positively with its effects on positive emotional state. We did not detect an effect of oxytocin on responses in the nucleus accumbens. Whole-brain analyses revealed that oxytocin attenuated medial prefrontal cortical deactivation specifically during anticipation of loss. Our findings demonstrate that intranasal administration of oxytocin modulates human midbrain and medial prefrontal function during motivated behavior. These findings suggest that endogenous oxytocin is a neurochemical mediator of reward behaviors in humans – even in a non-social context – and that the oxytocinergic system is a potential target of pharmacotherapy for psychiatric disorders that involve dysfunction of reward circuitry. PMID:27614896

  10. Oxytocin, stress and social behavior: neurogenetics of the human oxytocin system.

    Science.gov (United States)

    Kumsta, Robert; Heinrichs, Markus

    2013-02-01

    The neuropeptide oxytocin has had key roles throughout mammalian evolution in the regulation of complex social cognition and behaviors, such as attachment, parental care, pair-bonding, as well as social exploration and recognition. Recently, studies have begun to provide evidence that the function of this neuropeptide is impaired in mental disorders associated with social deficits. In this review, we focus on the genetic mechanisms of inter-individual variation in the social neuropeptide signaling. We discuss molecular genetic studies which identified variations in specific genes contributing to individual differences in social behavior and cognition, with a focus on the gene coding for the oxytocin receptor (OXTR) emerging as a particularly promising candidate. We conclude that molecular studies are warranted to elucidate functional consequences of variants that have shown stable associations with sociobehavioral phenotypes. With regard to the variability in individual responses to oxytocin administration, we advocate the need for pharmacogenetic approaches in order to test how the efficacy of oxytocin administration is modulated by genetic variation of OXTR or other genes involved in oxytocin signaling. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Gastroparesis is associated with oxytocin deficiency, oesophageal dysmotility with hyperCCKemia, and autonomic neuropathy with hypergastrinemia

    DEFF Research Database (Denmark)

    Borg, Julia; Melander, Olle; Johansson, Linda

    2009-01-01

    . They further received a fat-rich meal, after which blood samples were collected and plasma frozen until analysed for hormonal concentrations. RESULTS: There was an increase in postprandial oxytocin plasma concentration in the group with normal gastric emptying (p = 0.015) whereas subjects with delayed gastric...... emptying had no increased oxytocin secretion (p = 0.114). Both CCK and gastrin levels increased after the meal, with no differences between subjects with normal respective delayed gastric emptying. The concentration of vasopressin did not increase after the meal. In patients with oesophageal dysmotility......, cholecystokinin (CCK), gastrin and vasopressin in plasma differ between diabetics with normal function and dysfunction in GI motility. METHODS: Nineteen patients with symptoms from the GI tract who had been examined with gastric emptying scintigraphy, oesophageal manometry, and deep-breathing test were included...

  12. Characterization of the neurohypophysial hormone gene loci in elephant shark and the Japanese lamprey: origin of the vertebrate neurohypophysial hormone genes

    Directory of Open Access Journals (Sweden)

    Brenner Sydney

    2009-02-01

    Full Text Available Abstract Background Vasopressin and oxytocin are mammalian neurohypophysial hormones with distinct functions. Vasopressin is involved mainly in osmoregulation and oxytocin is involved primarily in parturition and lactation. Jawed vertebrates contain at least one homolog each of vasopressin and oxytocin, whereas only a vasopressin-family hormone, vasotocin, has been identified in jawless vertebrates. The genes encoding vasopressin and oxytocin are closely linked tail-to-tail in eutherian mammals whereas their homologs in chicken, Xenopus and coelacanth (vasotocin and mesotocin are linked tail-to-head. In contrast, their pufferfish homologs, vasotocin and isotocin, are located on the same strand of DNA with isotocin located upstream of vasotocin and separated by five genes. These differences in the arrangement of the two genes in different bony vertebrate lineages raise questions about their origin and ancestral arrangement. To trace the origin of these genes, we have sequenced BAC clones from the neurohypophysial gene loci in a cartilaginous fish, the elephant shark (Callorhinchus milii, and in a jawless vertebrate, the Japanese lamprey (Lethenteron japonicum. We have also analyzed the neurohypophysial hormone gene locus in an invertebrate chordate, the amphioxus (Branchiostoma floridae. Results The elephant shark neurohypophysial hormone genes encode vasotocin and oxytocin, and are linked tail-to-head like their homologs in coelacanth and non-eutherian tetrapods. Besides the hypothalamus, the two genes are also expressed in the ovary. In addition, the vasotocin gene is expressed in the kidney, rectal gland and intestine. These expression profiles indicate a paracrine role for the two hormones. The lamprey locus contains a single neurohypophysial hormone gene, the vasotocin. The synteny of genes in the lamprey locus is conserved in elephant shark, coelacanth and tetrapods but disrupted in teleost fishes. The amphioxus locus encodes a single

  13. Hormone assay

    International Nuclear Information System (INIS)

    Eisentraut, A.M.

    1977-01-01

    An improved radioimmunoassay is described for measuring total triiodothyronine or total thyroxine levels in a sample of serum containing free endogenous thyroid hormone and endogenous thyroid hormone bound to thyroid hormone binding protein. The thyroid hormone is released from the protein by adding hydrochloric acid to the serum. The pH of the separated thyroid hormone and thyroid hormone binding protein is raised in the absence of a blocking agent without interference from the endogenous protein. 125 I-labelled thyroid hormone and thyroid hormone antibodies are added to the mixture, allowing the labelled and unlabelled thyroid hormone and the thyroid hormone antibody to bind competitively. This results in free thyroid hormone being separated from antibody bound thyroid hormone and thus the unknown quantity of thyroid hormone may be determined. A thyroid hormone test assay kit is described for this radioimmunoassay. It provides a 'single tube' assay which does not require blocking agents for endogenous protein interference nor an external solid phase sorption step for the separation of bound and free hormone after the competitive binding step; it also requires a minimum number of manipulative steps. Examples of the assay are given to illustrate the reproducibility, linearity and specificity of the assay. (UK)

  14. Oxytocin: parallel processing in the social brain?

    Science.gov (United States)

    Dölen, Gül

    2015-06-01

    Early studies attempting to disentangle the network complexity of the brain exploited the accessibility of sensory receptive fields to reveal circuits made up of synapses connected both in series and in parallel. More recently, extension of this organisational principle beyond the sensory systems has been made possible by the advent of modern molecular, viral and optogenetic approaches. Here, evidence supporting parallel processing of social behaviours mediated by oxytocin is reviewed. Understanding oxytocinergic signalling from this perspective has significant implications for the design of oxytocin-based therapeutic interventions aimed at disorders such as autism, where disrupted social function is a core clinical feature. Moreover, identification of opportunities for novel technology development will require a better appreciation of the complexity of the circuit-level organisation of the social brain. © 2015 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.

  15. Oxytocin and Estrogen Receptor β in the Brain: An Overview.

    Science.gov (United States)

    Acevedo-Rodriguez, Alexandra; Mani, Shaila K; Handa, Robert J

    2015-01-01

    Oxytocin (OT) is a neuropeptide synthesized primarily by neurons of the paraventricular and supraoptic nuclei of the hypothalamus. These neurons have axons that project into the posterior pituitary and release OT into the bloodstream to promote labor and lactation; however, OT neurons also project to other brain areas where it plays a role in numerous brain functions. OT binds to the widely expressed OT receptor (OTR), and, in doing so, it regulates homeostatic processes, social recognition, and fear conditioning. In addition to these functions, OT decreases neuroendocrine stress signaling and anxiety-related and depression-like behaviors. Steroid hormones differentially modulate stress responses and alter OTR expression. In particular, estrogen receptor β activation has been found to both reduce anxiety-related behaviors and increase OT peptide transcription, suggesting a role for OT in this estrogen receptor β-mediated anxiolytic effect. Further research is needed to identify modulators of OT signaling and the pathways utilized and to elucidate molecular mechanisms controlling OT expression to allow better therapeutic manipulations of this system in patient populations.

  16. Testosterone, oxytocin, and the development of human parental care.

    Science.gov (United States)

    Gordon, Ilanit; Pratt, Maayan; Bergunde, Katharina; Zagoory-Sharon, Orna; Feldman, Ruth

    2017-07-01

    The steroid testosterone (T) and neuropeptide oxytocin (OT) have each been implicated in the development of parental care in humans and animals, yet very little research addressed the interaction between these hormones at the transition to parenthood in mothers and fathers. One hundred and sixty mothers and fathers (80 couples) were visited 1 and 6months after the birth of their first child, plasma OT and T were assayed at each time-point, and interactions between each parent and the infant were observed and micro-coded for two key parental behaviors; affectionate touch and parent-infant synchrony. T showed gender-specific effects. While paternal T was individually stable across the first six months of parenting and predicted lower father-infant synchrony, maternal T was neither stable nor predictive of maternal behavior. An interaction of OT and T showed that T has complex modulatory effects on the relations of OT and parenting. Slope analysis revealed that among fathers, only when T was high (+1SD), negative associations emerged between OT and father affectionate touch. In contrast, among mothers, the context of high T was related to a positive association between OT and maternal touch. Our findings, the first to test the interaction of OT and T in relation to observed maternal behavior, underscore the need for much further research on the complex bidirectional effects of steroid and neuropeptide systems on human mothering and fathering. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Comparative study on the effects of type 1 and type 2 diabetes on structural changes and hormonal output of the adrenal cortex in male Wistar rats

    Directory of Open Access Journals (Sweden)

    Elahi-Moghaddam Zohreh

    2013-01-01

    Full Text Available Abstract Introduction Diabetes is one of the most common endocrine disorders characterized by hyperglycemia due to defects in insulin secretion, insulin function, or both. Causing dysfunction in the body general metabolism, diabetes-induced chronic hyperglycemia leads to alterations in those endocrine glands involved in regulating the body metabolism. In this line, the present study has been conducted to investigate the effects of type 1 and type 2 diabetes on the structural changes and hormonal output of the adrenal cortex in male Wistar rat. Methods Eighteen male Wistar rats were divided into three groups including control, experimental type 1 diabetes (subcutaneous injection of 135 mg/kg alloxan and experimental type 2 diabetes (8 weeks treatment with drinking water containing 10% fructose. Two months after the induction of both types of diabetes, the level of blood biochemical factors (glucose, insulin, cortisol, triglycerides, cholesterol, LDL, and HDL were measured. Structural changes of the adrenal cortex were then evaluated, using stereological techniques. Results Serum biochemical analysis showed significant difference in the levels of glucose, triglycerides, insulin and cortisol in experimental groups, compared to the control. The results of structural alterations were also indicative of increase in adrenal cortex volume in both types of diabetes. Conclusion Probably through increasing HPA axis activity, type1 diabetes-induced hyperglycemia leads to adrenal hypertrophy and increase the hormonal output of adrenal gland.

  18. Approaches Mediating Oxytocin Regulation of the Immune System.

    Science.gov (United States)

    Li, Tong; Wang, Ping; Wang, Stephani C; Wang, Yu-Feng

    2016-01-01

    The hypothalamic neuroendocrine system is mainly composed of the neural structures regulating hormone secretion from the pituitary gland and has been considered as the higher regulatory center of the immune system. Recently, the hypothalamo-neurohypophysial system (HNS) emerged as an important component of neuroendocrine-immune network, wherein the oxytocin (OT)-secreting system (OSS) plays an essential role. The OSS, consisting of OT neurons in the supraoptic nucleus, paraventricular nucleus, their several accessory nuclei and associated structures, can integrate neural, endocrine, metabolic, and immune information and plays a pivotal role in the development and functions of the immune system. The OSS can promote the development of thymus and bone marrow, perform immune surveillance, strengthen immune defense, and maintain immune homeostasis. Correspondingly, OT can inhibit inflammation, exert antibiotic-like effect, promote wound healing and regeneration, and suppress stress-associated immune disorders. In this process, the OSS can release OT to act on immune system directly by activating OT receptors or through modulating activities of other hypothalamic-pituitary-immune axes and autonomic nervous system indirectly. However, our understandings of the role of the OSS in neuroendocrine regulation of immune system are largely incomplete, particularly its relationship with other hypothalamic-pituitary-immune axes and the vasopressin-secreting system that coexists with the OSS in the HNS. In addition, it remains unclear about the relationship between the OSS and peripherally produced OT in immune regulation, particularly intrathymic OT that is known to elicit central immunological self-tolerance of T-cells to hypophysial hormones. In this work, we provide a brief review of current knowledge of the features of OSS regulation of the immune system and of potential approaches that mediate OSS coordination of the activities of entire neuroendocrine-immune network.

  19. Oxytocin improves synchronisation in leader-follower interaction

    DEFF Research Database (Denmark)

    Gebauer, L.; Witek, M. A. G.; Hansen, N. C.

    2016-01-01

    , there was no effect when following a regular metronome or when both tappers were mutually adapting to each other. Furthermore, relative to their self-paced tapping partners, oxytocin followers were less variable than placebo followers. Our data suggests that oxytocin improves synchronisation to an unresponsive...

  20. Oxytocin: the neuropeptide of love reveals some of its secrets.

    Science.gov (United States)

    Neumann, Inga D

    2007-04-01

    The neuropeptide oxytocin is synthesized in the brain and released from neurohypophyseal terminals into the blood and within defined brain regions that regulate emotional, cognitive, and social behaviors. A recent study of CD38-/- mice (Jin et al., 2007) has demonstrated an essential role for the transmembrane receptor CD38 in secretion of oxytocin into the blood.

  1. Intranasal Oxytocin Failed to Affect Chimpanzee (Pan troglodytes) Social Behavior

    Science.gov (United States)

    Calcutt, Sarah E.; Burke, Kimberly; de Waal, Frans B. M.

    2017-01-01

    Oxytocin has been suggested as a treatment to promote positive social interactions in people with Autism Spectrum Disorders (ASD). However, it is difficult to test this effect outside of the laboratory in realistic social situations. One way to resolve this issue is to study behavioral changes in closely related species with complex social relationships, such as chimpanzees. Here, we use captive, socially housed chimpanzees to evaluate the effects of oxytocin in a socially complex environment. After administering intranasal oxytocin or a placebo to an individual chimpanzee (total n = 8), she was returned to her social group. An experimenter blind to the condition measured the subject's social behavior. We failed to find a behavioral difference between conditions. As one of the goals for oxytocin administration as a treatment for ASD is increasing prosocial behaviors during ‘real world’ encounters, it is problematic that we failed to detect behavioral changes in our closest living relatives. However, our null findings may be related to methodological challenges such as determining an effective dose of oxytocin for chimpanzees and how long oxytocin takes to cross the blood-brain barrier. Thus, more research on intranasal oxytocin dosing and uptake are needed to continue exploring whether oxytocin changes social behavior in naturalistic settings and as a treatment for ASD. PMID:28845444

  2. Oxytocin and the Biopsychology of Performance in Team Sports

    NARCIS (Netherlands)

    Pepping, Gert-Jan; Timmermans, Erik J.

    2012-01-01

    Little is known about the biopsychological underpinnings of expert performance in team sports. In this paper we show that there is a vast support for oxytocin as a neuropeptide involved in the encouragement of important processes linked to greater team performance in sport. We argue that oxytocin is

  3. Evolution of oxytocin pathways in the brain of vertebrates

    Directory of Open Access Journals (Sweden)

    H. Sophie Knobloch

    2014-02-01

    Full Text Available The central oxytocin system transformed tremendously during the evolution, thereby adapting to the expanding properties of species. In more basal vertebrates (paraphyletic taxon Anamnia, which includes agnathans, fish and amphibians, magnocellular neurosecretory neurons producing oxytocin, vasopressin and their homologs reside in the wall of the third ventricle of the hypothalamus composing a single hypothalamic structure, the preoptic nucleus. This nucleus further diverged in advanced vertebrates (monophyletic taxon Amniota, which includes reptiles, birds and mammals into the paraventricular and supraoptic nuclei with accessory nuclei between them. The individual magnocellular neurons underwent a process of transformation from primitive uni- or bipolar neurons into highly differentiated neurons. Due to these microanatomical and cytological changes, the ancient release modes of oxytocin into the cerebrospinal fluid were largely replaced by vascular release. However, the most fascinating feature of the progressive transformations of the oxytocin system has been the expansion of oxytocin axonal projections to forebrain regions. In the present review we provide a background on these evolutionary advancements. Furthermore, we draw attention to the non-synaptic axonal release in small and defined brain regions with the aim to clearly distinguish this way of oxytocin action from the classical synaptic transmission on one side and from dendritic release followed by a global diffusion on the other side. Finally, we will summarize the effects of oxytocin and its homologs on pro-social reproductive behaviors in representatives of the phylogenetic tree and will propose anatomically plausible pathways of oxytocin release contributing to these behaviors in basal vertebrates and amniots.

  4. Oxytocin augmentation: Poison or potion in the multipara? | Cluver ...

    African Journals Online (AJOL)

    Oxytocin is one of the most commonly used drugs in obstetric practice but it is also the drug associated with the most preventable adverse events in childbirth. In this review we look at the use of oxytocin augmentation in the multigravida. We look at the concept of whether the multigravida is different to the primigravida.

  5. Sex differences in methamphetamine seeking in rats: impact of oxytocin.

    Science.gov (United States)

    Cox, Brittney M; Young, Amy B; See, Ronald E; Reichel, Carmela M

    2013-10-01

    Previous evidence in an animal model of drug self-administration and drug seeking showed that acute oxytocin decreased methamphetamine (meth) seeking in male rats, suggesting potential clinical efficacy for the treatment of psychostimulant addiction. However, based on the well-established role of oxytocin in reproduction and pair bond formation, it is important to know how this effect extrapolates to females. Here, we tested whether oxytocin (1mg/kg, IP) would decrease meth seeking in female rats across various stages of the estrous cycle (Experiment 1). Freely cycling Long Evans female rats self-administered meth (IV) in 2-h daily sessions, followed by daily extinction sessions. Following extinction, rats received oxytocin (0, 0.3, or 1mg/kg, IP) 30min before a meth priming injection (1mg/kg, IP) to assess reinstatement of meth seeking. Next, we examined the effects of oxytocin on motivated meth- and sucrose-taking and seeking in male and female rats. In separate experiments, males and females self-administered meth (Experiment 2) or sucrose (Experiment 3) until responding was stabilized along a fixed ratio (FR) 5 schedule of reinforcement. Subsequently, rats received either oxytocin or vehicle prior to self-administration along a progressive ratio (PR) schedule of reinforcement. Rats were subsequently tested for cue-, meth-, and stress-induced reinstatement after pretreatment with oxytocin or vehicle. While oxytocin reduced meth seeking in females, we found that estrous cycle stage (as determined from vaginal cytology) did not influence meth-primed reinstatement or the ability of oxytocin to decrease reinstatement of meth seeking. Oxytocin reduced PR responding for meth only in females. Females responded more than males during cue-induced reinstatement of meth and sucrose seeking, and oxytocin reduced this responding only in meth females. In both sexes, oxytocin attenuated meth seeking in response to a meth prime and yohimbine (a pharmacological stressor). The

  6. Oxytocin and Social Cognition in Affective and Psychotic Disorders

    Science.gov (United States)

    Perez-Rodriguez, M. Mercedes; Mahon, Katie; Russo, Manuela; Ungar, Allison K.; Burdick, Katherine E.

    2014-01-01

    Impairments in social cognition are now recognized as core illness features in psychotic and affective disorders. Despite the significant disability caused by social cognitive abnormalities, treatments for this symptom dimension are lacking. Here, we describe the evidence demonstrating abnormalities in social cognition in schizophrenia, major depressive disorder, and bipolar disorder, as well as the neurobiology of social cognition including the role of oxytocin. We then review clinical trials of oxytocin administration in psychotic and affective disorders and the impact of this agent on social cognition. To date, several studies have demonstrated that oxytocin may improve social cognition in schizophrenia; too few studies have been conducted in affective disorders to determine the effect of oxytocin on social cognition in these disorders. Future work is needed to clarify which aspects of social cognition may be improved with oxytocin treatment in psychotic and affective disorders. PMID:25153535

  7. Life in groups: the roles of oxytocin in mammalian sociality

    Directory of Open Access Journals (Sweden)

    Allison eAnacker

    2013-12-01

    Full Text Available In recent decades, scientific understanding of the many roles of oxytocin in social behavior has advanced tremendously. The focus of this research has been on maternal attachments and reproductive pair-bonds, and much less is known about the substrates of sociality outside of reproductive contexts. It is now apparent that oxytocin influences many aspects of social behavior including recognition, trust, empathy, and other components of the behavioral repertoire of social species. This review provides a comparative perspective on the contributions of oxytocin to life in mammalian social groups. We provide background on the functions of oxytocin in maternal attachments and the early social environment, and give an overview of the role of oxytocin circuitry in support of different mating systems. We then introduce peer relationships in group-living rodents as a means for studying the importance of oxytocin in non-reproductive affiliative behaviors. We review species differences in oxytocin receptor distributions in solitary and group-living species of South American tuco-tucos and in African mole-rats, as well as singing mice. We discuss variation in oxytocin receptor levels with seasonal changes in social behavior in female meadow voles, and the effects of oxytocin manipulations on peer huddling behavior. Finally, we discuss avenues of promise for future investigation, and relate current findings to research in humans and non-human primates. There is growing evidence that oxytocin is involved in social selectivity, including increases in aggression toward social outgroups and decreased huddling with unfamiliar individuals, which may support existing social structures or relationships at the expense of others. Oxytocin’s effects reach beyond maternal attachment and pair bonds to play a role in affiliative behavior underlying friendships, organization of broad social structures, and maintenance of established social relationships with individuals

  8. Hormones as Difference Makers in Cognitive and Socioemotional Aging Processes

    Directory of Open Access Journals (Sweden)

    Natalie eEbner

    2015-01-01

    Full Text Available Aging is associated with well-recognized alterations in brain function, some of which are reflected in cognitive decline. While less appreciated, there is also considerable evidence of socioemotional changes later in life, some of which are beneficial. In this review, we examine age-related changes and individual differences in four neuroendocrine systems—cortisol, estrogen, testosterone, and oxytocin—as difference makers in these processes. This suite of interrelated hormonal systems actively coordinates regulatory processes in brain and behavior throughout development, and their level and function fluctuate during the aging process. Despite these facts, their specific impact in cognitive and socioemotional aging has received relatively limited study. It is known that chronically elevated levels of the stress hormone cortisol exert neurotoxic effects on the aging brain with negative impacts on cognition and socioemotional functioning. In contrast, the sex hormones estrogen and testosterone appear to have neuroprotective effects in cognitive aging, but may decrease prosociality. Higher levels of the neuropeptide oxytocin benefit socioemotional functioning, but little is known about the effects of oxytocin on cognition or about age-related changes in the oxytocin system. In this paper, we will review the role of these hormones in the context of cognitive and socioemotional aging. In particular, we address the aforementioned gap in the literature by: 1 examining both singular actions and interrelations of these four hormonal systems; 2 exploring their correlations and causal relationships with aspects of cognitive and socioemotional aging; and 3 considering multilevel internal and external influences on these hormone systems within the framework of explanatory pluralism. We conclude with a discussion of promising future research directions.

  9. Questioning the role of pituitary oxytocin in parturition: spontaneous onset of labor in women with panhypopituitarism--a case series.

    Science.gov (United States)

    Shinar, Shiri; Many, Ariel; Maslovitz, Sharon

    2016-02-01

    Oxytocin, a nanopeptide secreted by the posterior pituitary gland, has well-established uterotonic activity. Its role in initiating the vigorous and regular contractions of the first stage of labor is still controversial. We report four cases of panhypopituitarism who had spontaneous onset of labor, undermining the role of maternal oxytocin in the first phase of labor. Four women with no residual pituitary function conceived through ovulation induction and were treated throughout pregnancy with thyroid replacement therapy, desmopressin and glucocorticoids. In all cases pituitary function was undetectable in repeated blood tests. We report their course of pregnancy and delivery. All four pregnancies progressed to term with hormonal replacement therapy. All cases went into spontaneous labor. Two women delivered vaginally unassisted by pharmacological intervention and two delivered by cesarean sections during active labor due to obstetrical indications. Three suffered postpartum hemorrhage. Lactation did not ensue in all four cases. Endogenous pituitary oxytocin is probably not obligatory for initiation of labor in the first phase of parturition. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. The Oxytocin Receptor (OXTR) Contributes to Prosocial Fund Allocations in the Dictator Game and the Social Value Orientations Task

    Science.gov (United States)

    Israel, Salomon; Lerer, Elad; Shalev, Idan; Uzefovsky, Florina; Riebold, Mathias; Laiba, Efrat; Bachner-Melman, Rachel; Maril, Anat; Bornstein, Gary; Knafo, Ariel; Ebstein, Richard P.

    2009-01-01

    Background Economic games observe social decision making in the laboratory that involves real money payoffs. Previously we have shown that allocation of funds in the Dictator Game (DG), a paradigm that illustrates costly altruistic behavior, is partially determined by promoter-region repeat region variants in the arginine vasopressin 1a receptor gene (AVPR1a). In the current investigation, the gene encoding the related oxytocin receptor (OXTR) was tested for association with the DG and a related paradigm, the Social Values Orientation (SVO) task. Methodology/Principal Findings Association (101 male and 102 female students) using a robust-family based test between 15 single tagging SNPs (htSNPs) across the OXTR was demonstrated with both the DG and SVO. Three htSNPs across the gene region showed significant association with both of the two games. The most significant association was observed with rs1042778 (p = 0.001). Haplotype analysis also showed significant associations for both DG and SVO. Following permutation test adjustment, significance was observed for 2–5 locus haplotypes (pprosocial decision making converges with a large body of animal research showing that oxytocin is an important social hormone across vertebrates including Homo sapiens. Individual differences in prosocial behavior have been shown by twin studies to have a substantial genetic basis and the current investigation demonstrates that common variants in the oxytocin receptor gene, an important element of mammalian social circuitry, underlie such individual differences. PMID:19461999

  11. Increased plasma concentrations of vasopressin, oxytocin, cortisol and the prostaglandin F2alpha metabolite during labour in the dog.

    Science.gov (United States)

    Olsson, K; Bergström, A; Kindahl, H; Lagerstedt, A-S

    2003-11-01

    This study investigated if the plasma vasopressin concentration increases during labour in the dog and whether the change in vasopressin correlates with that of oxytocin, 15-ketodihydro-PGF2alpha and cortisol. Five beagle dogs each delivered three to seven puppies. Blood samples were taken from a catheter inserted into the cephalic vein during labour and by venepuncture during the other periods. Vasopressin concentration increased from 2 +/- 0 pmol L-1 (anoestrus) to 26 +/- 11 pmol L-1 at the birth of the first puppy, remained high at the birth of the second puppy and then decreased. Oxytocin increased from 63 +/- 5 pmol L-1 (anoestrus) to 166 +/- 19 pmol L-1 at the birth of the first puppy and remained elevated throughout labour. The PGF2alpha metabolite concentration increased from 0.2 +/- 0.0 nmol L-1 (anoestrus) to 66 +/- 17 nmol L-1 at the birth of the first puppy and remained elevated 1 h after the completion of parturition. The cortisol concentration increased from 49 +/- 9 nmol L-1 (anoestrus) to 242 +/- 35 nmol L-1 at the birth of the first puppy, remained high during the birth of the second puppy and then declined. The plasma level of vasopressin was strongly correlated with that of cortisol but less with that of the PGF2alpha metabolite, and not significantly with the concentration of oxytocin. This indicates that the four hormones play different roles during labour in the dog.

  12. Oxytocin's role on the cardiorespiratory activity of endotoxemic rats.

    Science.gov (United States)

    Elorza-Ávila, Ana Rosa; Reyes-Lagos, José Javier; Hadamitzky, Martin; Peña-Castillo, Miguel Ángel; Echeverría, Juan Carlos; Ortiz-Pedroza, María Del Rocío; Lückemann, Laura; Schedlowski, Manfred; Pacheco-López, Gustavo

    2017-02-01

    Recent findings concerning oxytocin indicate its anti-inflammatory, cardioprotective and parasympathetic modulating properties. In this study, we investigated the effects of systemically applied oxytocin on the cardiorespiratory activity in a rodent model of moderate endotoxemia. Telemetrically recorded electrocardiogram (ECGs) from animals which received lipopolysaccharide (LPS); oxytocin (Ox); lipopolysaccharide+oxytocin (LPS+Ox), or vehicle (V) were analyzed using the ECG-derived respiration (EDR) technique to estimate the respiratory rate. The mean R-R interval and the spectral parameters of heart rate variability (HRV), such as the natural logarithm of the high frequency (lnHF) and low frequency (lnLF) components were also estimated up to 24h after treatment. The endotoxemic animals (LPS) showed an elevated respiratory rate as well as a reduced mean R-R interval, lnHF and lnLF components compared to controls (V) from +5 to +12h after the treatment. The administration of oxytocin significantly attenuated the hyperventilation produced by the LPS-induced endotoxemia (LPS+Ox) and restored the values of the mean R-R interval and such spectral parameters at different time points. Our results support the existence of a link among the respiratory, cardiovascular, and immune systems in which oxytocin seems to act as a potential cardioprotective peptide by favoring cardiac cholinergic autonomic coupling. As a result, oxytocin diminished animal's endotoxemic tachypnea and restored the cardiorespiratory interactions, which was indicated by the spectral components of HRV. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Oxytocin modulates human communication by enhancing cognitive exploration.

    Science.gov (United States)

    de Boer, Miriam; Kokal, Idil; Blokpoel, Mark; Liu, Rui; Stolk, Arjen; Roelofs, Karin; van Rooij, Iris; Toni, Ivan

    2017-12-01

    Oxytocin is a neuropeptide known to influence how humans share material resources. Here we explore whether oxytocin influences how we share knowledge. We focus on two distinguishing features of human communication, namely the ability to select communicative signals that disambiguate the many-to-many mappings that exist between a signal's form and meaning, and adjustments of those signals to the presumed cognitive characteristics of the addressee ("audience design"). Fifty-five males participated in a randomized, double-blind, placebo controlled experiment involving the intranasal administration of oxytocin. The participants produced novel non-verbal communicative signals towards two different addressees, an adult or a child, in an experimentally-controlled live interactive setting. We found that oxytocin administration drives participants to generate signals of higher referential quality, i.e. signals that disambiguate more communicative problems; and to rapidly adjust those communicative signals to what the addressee understands. The combined effects of oxytocin on referential quality and audience design fit with the notion that oxytocin administration leads participants to explore more pervasively behaviors that can convey their intention, and diverse models of the addressees. These findings suggest that, besides affecting prosocial drive and salience of social cues, oxytocin influences how we share knowledge by promoting cognitive exploration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Factors associated with higher oxytocin requirements in labor.

    Science.gov (United States)

    Frey, Heather A; Tuuli, Methodius G; England, Sarah K; Roehl, Kimberly A; Odibo, Anthony O; Macones, George A; Cahill, Alison G

    2015-09-01

    To identify clinical characteristics associated with high maximum oxytocin doses in women who achieve complete cervical dilation. A retrospective nested case-control study was performed within a cohort of all term women at a single center between 2004 and 2008 who reached the second stage of labor. Cases were defined as women who had a maximum oxytocin dose during labor >20 mu/min, while women in the control group had a maximum oxytocin dose during labor of ≤20 mu/min. Exclusion criteria included no oxytocin administration during labor, multiple gestations, major fetal anomalies, nonvertex presentation, and prior cesarean delivery. Multiple maternal, fetal, and labor factors were evaluated with univariable analysis and multivariable logistic regression. Maximum oxytocin doses >20 mu/min were administered to 108 women (3.6%), while 2864 women received doses ≤20 mu/min. Factors associated with higher maximum oxytocin dose after adjusting for relevant confounders included maternal diabetes, birthweight >4000 g, intrapartum fever, administration of magnesium, and induction of labor. Few women who achieve complete cervical dilation require high doses of oxytocin. We identified maternal, fetal and labor factors that characterize this group of parturients.

  15. The ventromedial hypothalamus oxytocin induces locomotor behavior regulated by estrogen.

    Science.gov (United States)

    Narita, Kazumi; Murata, Takuya; Matsuoka, Satoshi

    2016-10-01

    Our previous studies demonstrated that excitation of neurons in the rat ventromedial hypothalamus (VMH) induced locomotor activity. An oxytocin receptor (Oxtr) exists in the VMH and plays a role in regulating sexual behavior. However, the role of Oxtr in the VMH in locomotor activity is not clear. In this study we examined the roles of oxytocin in the VMH in running behavior, and also investigated the involvement of estrogen in this behavioral change. Microinjection of oxytocin into the VMH induced a dose-dependent increase in the running behavior in male rats. The oxytocin-induced running activity was inhibited by simultaneous injection of Oxtr-antagonist, (d(CH2)5(1), Try(Me)(2), Orn(8))-oxytocin. Oxytocin injection also induced running behavior in ovariectomized (OVX) female rats. Pretreatment of the OVX rats with estrogen augmented the oxytocin-induced running activity twofold, and increased the Oxtr mRNA in the VMH threefold. During the estrus cycle locomotor activity spontaneously increased in the dark period of proestrus. The Oxtr mRNA was up-regulated in the proestrus afternoon. Blockade of oxytocin neurotransmission by its antagonist before the onset of the dark period of proestrus decreased the following nocturnal locomotor activity. These findings demonstrate that Oxtr in the VMH is involved in the induction of running behavior and that estrogen facilitates this effect by means of Oxtr up-regulation, suggesting the involvement of oxytocin in the locomotor activity of proestrus female rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Brief Report: Oxytocin Enhances Paternal Sensitivity to a Child with Autism--A Double-Blind Within-Subject Experiment with Intranasally Administered Oxytocin

    Science.gov (United States)

    Naber, Fabienne B. A.; Poslawsky, Irina E.; van Ijzendoorn, Marinus H.; van Engeland, Herman; Bakermans-Kranenburg, Marian J.

    2013-01-01

    Oxytocin seems associated with parenting style, and experimental work showed positive effects of intranasally administered oxytocin on parenting style of fathers. Here, the first double-blind, placebo-controlled, within-subject experiment with intranasal oxytocin administration to fathers of children with autism spectrum disorder (ASD) is…

  17. Depression in early adolescence: Contributions from relational aggression and variation in the oxytocin receptor gene.

    Science.gov (United States)

    Kushner, Shauna C; Herzhoff, Kathrin; Vrshek-Schallhorn, Suzanne; Tackett, Jennifer L

    2018-01-01

    Interpersonal stress arising from relational aggression (RA)-the intentional effort to harm others via rejection and exclusion-may increase risk for depression in youth. Biological vulnerabilities related to the hormone oxytocin, which affects social behavior and stress responses, may exacerbate this risk. In a community sample of 307 youth (52% female; age range = 10-14 years), we tested whether (1) the association between RA and subsequent depressive symptoms was mediated through social problems and (2) a single nucleotide polymorphism (rs53576) in the oxytocin receptor gene (OXTR) moderated this indirect association between RA and depression, where GG homozygotes are predicted to be more sensitive to the effects of social problems than A-allele carriers. Youth-reported RA and depressive symptoms were measured using a structured interview and a questionnaire, respectively. DNA was extracted from saliva collected with Oragene kits. Consistent with the interpersonal theory of depression, the association between relational aggression and subsequent depressive symptoms was mediated by social problems. This indirect effect was further moderated by rs53576 genotype, such that GG homozygotes showed a stronger mediation effect than A-carriers. These results suggest that rs53576 variants confer vulnerability for depression within the context of interpersonal risk factors, such that youth with the GG genotype may be particularly sensitive to the social consequences resulting from RA. © 2017 Wiley Periodicals, Inc.

  18. Oxytocin and Vasopressin: Linking Pituitary Neuropeptides and their Receptors to Social Neurocircuits

    Directory of Open Access Journals (Sweden)

    Danielle Andrea Baribeau

    2015-09-01

    Full Text Available Oxytocin and vasopressin are pituitary neuropeptides that have been shown to affect social processes in mammals. There is growing interest in these molecules and their receptors as potential precipitants of, and/or treatments for, social deficits in neurodevelopmental disorders, including autism spectrum disorder. Numerous behavioral-genetic studies suggest that there is an association between these peptides and individual social abilities; however, an explanatory model that links hormonal activity at the receptor level to complex human behavior remains elusive. The following review summarizes the known associations between the oxytocin and vasopressin neuropeptide systems and social neurocircuits in the brain. Following a micro- to macro- level trajectory, current literature on the synthesis and secretion of these peptides, and the structure, function and distribution of their respective receptors is first surveyed. Next, current models regarding the mechanism of action of these peptides on microcircuitry and other neurotransmitter systems are discussed. Functional neuroimaging evidence on the acute effects of exogenous administration of these peptides on brain activity is then reviewed. Overall, a model in which the local neuromodulatory effects of pituitary neuropeptides on brainstem and basal forebrain regions strengthen signaling within social neurocircuits proves appealing. However, these findings are derived from animal models; more research is needed to clarify the relevance of these mechanisms to human behavior and treatment of social deficits in neuropsychiatric disorders.

  19. EFFECT OF OXYTOCIN MASSAGE USING LAVENDER ESSENTIAL OIL ON PROLACTIN LEVEL AND BREAST MILK PRODUCTION IN PRIMIPAROUS MOTHERS AFTER CAESAREAN DELIVERY

    Directory of Open Access Journals (Sweden)

    Panglukies Ratna Agustie

    2017-08-01

    Full Text Available Background: Low milk production is one of the barries to exclusive breastfeeding. Oxytocin massage is considered as an alternative treatment, which combined with lavender essential oil as an aromatherapy. Objective: This study aims to examine the effect of oxytocin massage using lavender essential oil on the increase of levels of prolactin and milk production in primiparaous mothers after caesarean section. Methods: This was a quasi-experimental study with non-equivalent control group design conducted in October-December 2016 at the General Hospital of Dr.H. Soewondo Kendal. There were 32 recruited by consecutive sampling, divided to be intervention (16 participants and control group (16 participants. Prolactin hormone levels were measured using Enzyme-linked immunosorbent assay (ELIZA, breast milk production was measured based on the indicators of milk volume, urination and defecation frequency and sleep duration of babies; and infant’s weight was also measured by digital scale. Data were analyzed using Mann Whitney and Wilcoxon test. Results: The mean difference of prolactin hormone level in control group was 17.82 ng / ml while mean of difference of hormone prolactin level in intervention group was 132.13 ng / ml. There were statistically significant differences between intervention and control group in prolactin levels (p-value 0.000, milk volume (p-value 0.000, infant weight (p-value 0.000, urination frequency (p-value 0.017, defecation frequency (p-value 0.002, and infant sleep duration (p-value 0.000. Conclusion: There was a significant effect of the oxytocin massage using lavender essential oil on the increase of breast milk production and prolactin levels. Therefore, oxytocin massage using lavender essential oil can be used as an alternative treatment for midwives and other health professionals in an effort to increase milk production in postpartum.

  20. Gastroparesis is associated with oxytocin deficiency, oesophageal dysmotility with hyperCCKemia, and autonomic neuropathy with hypergastrinemia

    Directory of Open Access Journals (Sweden)

    Uvnäs-Moberg Kerstin

    2009-02-01

    Full Text Available Abstract Background Gastrointestinal (GI dysmotility and autonomic neuropathy are common problems among diabetics with largely unknown aetiology. Many peptides are involved in the autonomic nervous system regulating the GI tract. The aim of this study was to examine if concentrations of oxytocin, cholecystokinin (CCK, gastrin and vasopressin in plasma differ between diabetics with normal function and dysfunction in GI motility. Methods Nineteen patients with symptoms from the GI tract who had been examined with gastric emptying scintigraphy, oesophageal manometry, and deep-breathing test were included. They further received a fat-rich meal, after which blood samples were collected and plasma frozen until analysed for hormonal concentrations. Results There was an increase in postprandial oxytocin plasma concentration in the group with normal gastric emptying (p = 0.015 whereas subjects with delayed gastric emptying had no increased oxytocin secretion (p = 0.114. Both CCK and gastrin levels increased after the meal, with no differences between subjects with normal respective delayed gastric emptying. The concentration of vasopressin did not increase after the meal. In patients with oesophageal dysmotility the basal level of CCK tended to be higher (p = 0.051 and those with autonomic neuropathy had a higher area under the curve (AUC of gastrin compared to normal subjects (p = 0.007. Conclusion Reduced postprandial secretion of oxytocin was found in patients with delayed gastric emptying, CCK secretion was increased in patients with oesophageal dysmotility, and gastrin secretion was increased in patients with autonomic neuropathy. The findings suggest that disturbed peptide secretion may be part of the pathophysiology of digestive complications in diabetics.

  1. Nasally-Administered Oxytocin Has Limited Effects on Owner-Directed Attachment Behavior in Pet Dogs (Canis lupus familiaris

    Directory of Open Access Journals (Sweden)

    Lauren E. Thielke

    2017-09-01

    Full Text Available The present study explored the effects of intranasal oxytocin, a naturally occurring hormone, on the behavior of pet dogs during an attachment test. Each dog participated in two testing sessions. On one visit saline was administered nasally, and on another, oxytocin was administered nasally. For half of the dogs (n = 20, solutions were administered with a Mucosal Atomization Device (MAD and for half of the dogs (n = 20, solutions were administered using a nasal spray bottle. Condition order was counterbalanced and a double-blind methodology was employed. Following a 30-min wait period after administration of solutions, dog-owner pairs participated in the Secure Base Test, a short attachment test consisting of three 2-min phases: (1 Baseline- the owner was present, dogs were able to freely explore the testing room (2 Alone- dogs were left alone in the testing room (3 Return- owners re-entered the room and were reunited with their dog. In each phase the dog was evaluated for contact seeking, exploration, and avoidance behaviors. Although, oxytocin administration was expected to increase owner-directed proximity and contact seeking behavior, this effect was not observed. In fact, in the baseline phase, dogs spent significantly more time seeking the proximity of their owners when they received saline than when they received OT (p < 0.05. Sex differences were also assessed for the behavioral variables of interest in the Secure Base Test, and results indicated that OT did not affect dogs' behavior in the alone phase, but when saline was administered, females spent significantly more time in contact with the door than males in the alone phase (p < 0.05. Overall, the effects of nasally administered oxytocin on attachment related behavior appeared to be limited or inconsistent for this pet dog population.

  2. Recovery from adolescent anorexia nervosa and associations with diurnal patterns of salivary stress hormones: a case report.

    Science.gov (United States)

    Oskis, Andrea; Loveday, Catherine; Hucklebridge, Frank; Wood, David; Clow, Angela

    2012-01-01

    In the neurodevelopment of adolescent anorexia nervosa (AN), dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is proposed to be a central component. Furthermore, a therapeutic milieu focusing on affect regulation can contribute much to treatment, given the emotional processing difficulties associated with this disorder. Studies of HPA axis function following such specialist treatments for adolescent AN, however, are rare. This study describes the diurnal pattern of HPA axis activation, including the cortisol awakening response (CAR), in a 16-year-old female diagnosed with AN both during illness and at clinical recovery following milieu therapy with a focus on affect regulation. Specialised single-case study statistics were used to assess whether the patient's data were significantly different from the healthy "norm" at illness and recovery. During illness, her measure of affective problems was outside of the normal range and cortisol and DHEA secretory profiles were significantly elevated across the diurnal period. However, at recovery both her affective state and HPA axis function became comparable to healthy controls. This case study suggests that salivary markers of HPA axis function can be feasibly incorporated into the clinical regime within a specialist adolescent AN residential service and could be used by clinicians to monitor prognosis and interventions.

  3. Recovery from Adolescent Anorexia Nervosa and Associations with Diurnal Patterns of Salivary Stress Hormones: A Case Report

    Directory of Open Access Journals (Sweden)

    Andrea Oskis

    2012-01-01

    Full Text Available In the neurodevelopment of adolescent anorexia nervosa (AN, dysregulation of the hypothalamic-pituitary-adrenal (HPA axis is proposed to be a central component. Furthermore, a therapeutic milieu focusing on affect regulation can contribute much to treatment, given the emotional processing difficulties associated with this disorder. Studies of HPA axis function following such specialist treatments for adolescent AN, however, are rare. This study describes the diurnal pattern of HPA axis activation, including the cortisol awakening response (CAR, in a 16-year-old female diagnosed with AN both during illness and at clinical recovery following milieu therapy with a focus on affect regulation. Specialised single-case study statistics were used to assess whether the patient's data were significantly different from the healthy “norm” at illness and recovery. During illness, her measure of affective problems was outside of the normal range and cortisol and DHEA secretory profiles were significantly elevated across the diurnal period. However, at recovery both her affective state and HPA axis function became comparable to healthy controls. This case study suggests that salivary markers of HPA axis function can be feasibly incorporated into the clinical regime within a specialist adolescent AN residential service and could be used by clinicians to monitor prognosis and interventions.

  4. Are behavioral effects of early experience mediated by oxytocin?

    Directory of Open Access Journals (Sweden)

    Karen Lisa Bales

    2011-05-01

    Full Text Available Early experiences can alter adaptive emotional responses necessary for social behavior as well as physiological reactivity in the face of challenge. In the highly social prairie vole (Microtus ochrogaster, manipulations in early life or hormonal treatments specifically targeted at the neuropeptides oxytocin (OT and arginine vasopressin (AVP, have long-lasting, often sexually-dimorphic, consequences for social behavior. Here we examine the hypothesis that behavioral changes associated with differential early experience, in this case handling the family during the first week of life, may be mediated by changes in OT or AVP or their brain receptors. Four early treatment groups were used, differing only in the amount of manipulation received during the first week of life. MAN1 animals were handled once on post-natal day 1; MAN1 treatment produces a pattern of behavior usually considered typical of this species, against which other groups were compared. MAN 1-7 animals were handled once a day for post-natal days 1-7, MAN 7 animals were handled once on post-natal day 7, and MAN0 animals received no handling during the first week of life. When tested following weaning, males in groups that had received manipulation during the first few days of life (MAN1 and MAN1-7 displayed higher alloparenting than other groups. Neuroendocrine measures, including OT receptor binding and OT and AVP immunoreactivity, varied by early treatment. In brain areas including the nucleus accumbens, bed nucleus of stria terminalis and lateral septum, MAN0 females showed increased OT receptor binding. MAN1 animals also displayed higher numbers of immunoreactive OT cell bodies in the supraoptic nucleus. Taken together these findings support the broader hypothesis that experiences in the first few days of life, mediated in part by sexually-dimorphic changes in neuropeptides, especially in the receptor for OT, may have adaptive consequences for sociality and emotion regulation.

  5. The human oxytocin gene promoter is regulated by estrogens.

    Science.gov (United States)

    Richard, S; Zingg, H H

    1990-04-15

    Gonadal steroids affect brain function primarily by altering the expression of specific genes, yet the specific mechanisms by which neuronal target genes undergo such regulation are unknown. Recent evidence suggests that the expression of the neuropeptide gene for oxytocin (OT) is modulated by estrogens. We therefore examined the possibility that this regulation occurred via a direct interaction of the estrogen-receptor complex with cis-acting elements flanking the OT gene. DNA-mediated gene transfer experiments were performed using Neuro-2a neuroblastoma cells and chimeric plasmids containing portions of the human OT gene 5'-glanking region linked to the chloramphenicol acetyltransferase gene. We identified a 19-base pair region located at -164 to -146 upstream of the transcription start site which is capable of conferring estrogen responsiveness to the homologous as well as to a heterologous promoter. The hormonal response is strictly dependent on the presence of intracellular estrogen receptors, since estrogen induced stimulation occurred only in Neuro-2a cells co-transfected with an expression vector for the human estrogen receptor. The identified region contains a novel imperfect palindrome (GGTGACCTTGACC) with sequence similarity to other estrogen response elements (EREs). To define cis-acting elements that function in synergism with the ERE, sequences 3' to the ERE were deleted, including the CCAAT box, two additional motifs corresponding to the right half of the ERE palindrome (TGACC), as well as a CTGCTAA heptamer similar to the "elegans box" found in Caenorhabditis elegans. Interestingly, optimal function of the identified ERE was fully independent of these elements and only required a short promoter region (-49 to +36). Our studies define a molecular mechanism by which estrogens can directly modulate OT gene expression. However, only a subset of OT neurons are capable of binding estrogens, therefore, direct action of estrogens on the OT gene may be

  6. Medial Prefrontal Cortex and HPA Axis Roles in Generation of PTSD-Like Symptoms in SPS Model

    Science.gov (United States)

    2012-09-01

    concentration of glutamine (a major precursor molecule for synthesis of neuronal glutamate) (Nicholls, 1994) was also attenuated in the mPFC. The concentration...glutamate used for neural transmission because glutamate is a precursor molecule for the synthesis of GABA (Cooper et al., 1996). There was no...onsecutive weight gain. The PL and IL were temporarily inactivated by infusion of the odium channel blocker, lidocaine HCL (Sigma–Aldrich, St. Louis, O) in

  7. The Hypothalamic-Pituitary-Adrenal Axis, Obesity, and Chronic Stress Exposure: Sleep and the HPA Axis in Obesity

    OpenAIRE

    Lucassen, Eliane A.; Cizza, Giovanni

    2012-01-01

    Obesity, exposure to stress and inadequate sleep are prevalent phenomena in modern society. In this review we focus on their relationships and critically evaluate causality. In obese individuals, one of the main stress systems, the hypothalamic-pituitary-adrenal axis, is altered, and concentrations of cortisol are elevated in adipose tissue due to elevated local activity of 11β-hydroxysteroid dehydrogenase (HSD) type 1. Short sleep and decreased sleep quality are also associated with obesity....

  8. Basal and stress-induced differences in HPA axis, 5-HT responsiveness, and hippocampal cell proliferation in two mouse lines

    NARCIS (Netherlands)

    Veenema, AH; Koolhaas, JM; De Kloet, ER; Pacak, K; Aguilera, B; Saban, E; Kvetnansky, R

    2004-01-01

    To characterize individual differences in neuroendocrine and neurochemical correlates of stress coping, two lines of wild house mice were studied. These mice are genetically selected for high and low aggression and show distinctly different behavioral strategies toward environmental stimuli. Long

  9. Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation.

    Science.gov (United States)

    Pagliaccio, David; Luby, Joan L; Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S; Belden, Andrew C; Botteron, Kelly N; Harms, Michael P; Barch, Deanna M

    2015-11-01

    Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within 4 hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9- to 14-year-olds; N = 120). Whole-brain regression analyses indicated that increasing genetic "risk" predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic "risk" and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation. The current results suggest that considering the unique and interacting effects of biological vulnerability and environmental risk factors may be key to understanding the development of altered amygdala functional connectivity, a potential factor in the risk trajectory for internalizing pathology. (c) 2015 APA, all rights reserved).

  10. Effect of maternal probiotic intervention on HPA axis, immunity and gut microbiota in a rat model of irritable bowel syndrome.

    Directory of Open Access Journals (Sweden)

    Javad Barouei

    Full Text Available OBJECTIVE: To examine whether maternal probiotic intervention influences the alterations in the brain-immune-gut axis induced by neonatal maternal separation (MS and/or restraint stress in adulthood (AS in Wistar rats. DESIGN: Dams had free access to drinking water supplemented with Bifidobacterium animalis subsp lactis BB-12® (3 × 10(9 CFU/mL and Propionibacterium jensenii 702 (8.0 × 10(8 CFU/mL from 10 days before conception until postnatal day (PND 22 (weaning day, or to control ad lib water. Offspring were subjected to MS from PND 2 to 14 or left undisturbed. From PND 83 to 85, animals underwent 30 min/day AS, or were left undisturbed as controls. On PND 24 and 86, blood samples were collected for corticosterone, ACTH and IgA measurement. Colonic contents were analysed for the composition of microflora and luminal IgA levels. RESULTS: Exposure to MS significantly increased ACTH levels and neonatal fecal counts of aerobic and anaerobic bacteria, E. coli, enterococci and clostridia, but reduced plasma IgA levels compared with non-MS animals. Animals exposed to AS exhibited significantly increased ACTH and corticosterone levels, decreased aerobic bacteria and bifidobacteria, and increased Bacteroides and E. coli counts compared to non-AS animals. MS coupled with AS induced significantly decreased anaerobes and clostridia compared with the non-stress adult controls. Maternal probiotic intervention significantly increased neonatal corticosterone levels which persisted until at least week 12 in females only, and also resulted in elevated adult ACTH levels and altered neonatal microflora comparable to that of MS. However, it improved plasma IgA responses, increased enterococci and clostridia in MS adults, increased luminal IgA levels, and restored anaerobes, bifidobacteria and E. coli to normal in adults. CONCLUSION: Maternal probiotic intervention induced activation of neonatal stress pathways and an imbalance in gut microflora. Importantly however, it improved the immune environment of stressed animals and protected, in part, against stress-induced disturbances in adult gut microflora.

  11. Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation

    Science.gov (United States)

    Pagliaccio, David; Luby, Joan L.; Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S.; Belden, Andrew C.; Botteron, Kelly N.; Harms, Michael P.; Barch, Deanna M.

    2015-01-01

    Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within four hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9–14 year olds; N=120). Whole-brain regression analyses indicated that increasing genetic ‘risk’ predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic ‘risk’ and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation. The current results suggest that considering the unique and interacting effects of biological vulnerability and environmental risk factors may be key to understanding the development of altered amygdala functional connectivity, a potential factor in the risk trajectory for internalizing pathology. PMID:26595470

  12. Sex differences in sleep, anhedonia, and HPA axis activity in a rat model of chronic social defeat

    Directory of Open Access Journals (Sweden)

    Gayle G. Page

    2016-06-01

    Full Text Available Repeated bouts of a major stressor such as social defeat are well known to induce a depression phenotype in male rats. Despite strong evidence and acknowledgement that women have a two-fold lifetime greater risk of developing major depression compared to men, the inclusion of female rats in studies employing social defeat are very rare; their absence is attributed to less aggressive interactions. This study sought to compare in male and female rats the impact of repeated social defeat, three times per week for four weeks, on the development of changes in sleep architecture and continuity, sucrose preference as a measure of anhedonia, changes in body weight, and basal plasma corticosterone levels. We found significant reductions in rapid eye movement sleep (REMS during the light phase in both females and males, and significant increases in numbers of vigilance state transitions during the early dark phase in females but not in males. Additionally, females exhibited significantly greater reductions in sucrose intake than males. On the other hand, no sex differences in significantly elevated basal corticosterone levels were evident, and only the males exhibited changes in body weight. Taken together these findings suggest that the inclusion of female rats in studies of social defeat may offer greater insights in studies of stress and depression.

  13. Oxytocin and the Biopsychology of Performance in Team Sports

    Science.gov (United States)

    Pepping, Gert-Jan; Timmermans, Erik J.

    2012-01-01

    Little is known about the biopsychological underpinnings of expert performance in team sports. In this paper we show that there is a vast support for oxytocin as a neuropeptide involved in the encouragement of important processes linked to greater team performance in sport. We argue that oxytocin is related to biopsychological processes aimed at convergence of emotions and moods between people, and in doing so it is a critical neuropeptide involved in the shaping of important team processes in sport such as trust, generosity, altruism, cohesion, cooperation, and social motivation, and also envy and gloating. Future research should examine the role of oxytocin in these essential components of sport performance. In particular, the link between oxytocin, emotional contagion and the cultivation of experiences of positive emotions is a worthwhile line of investigation for sport participation and development as well as high performance in sport. PMID:22997498

  14. Oxytocin and the biopsychology of performance in team sports.

    Science.gov (United States)

    Pepping, Gert-Jan; Timmermans, Erik J

    2012-01-01

    Little is known about the biopsychological underpinnings of expert performance in team sports. In this paper we show that there is a vast support for oxytocin as a neuropeptide involved in the encouragement of important processes linked to greater team performance in sport. We argue that oxytocin is related to biopsychological processes aimed at convergence of emotions and moods between people, and in doing so it is a critical neuropeptide involved in the shaping of important team processes in sport such as trust, generosity, altruism, cohesion, cooperation, and social motivation, and also envy and gloating. Future research should examine the role of oxytocin in these essential components of sport performance. In particular, the link between oxytocin, emotional contagion and the cultivation of experiences of positive emotions is a worthwhile line of investigation for sport participation and development as well as high performance in sport.

  15. Empathy toward strangers triggers oxytocin release and subsequent generosity.

    Science.gov (United States)

    Barraza, Jorge A; Zak, Paul J

    2009-06-01

    Empathy is related to a variety of prosocial behaviors, but the brain mechanisms producing the experience of empathy have not been fully characterized. This study investigated whether the experience of empathy raises oxytocin levels and affects subsequent generosity toward strangers. Short video clips of an emotional scene and an unemotional scene were used as stimuli. Participants rated the emotions they experienced and then played a $40 ultimatum game to gauge their generosity. We found that empathy was associated with a 47% increase in oxytocin from baseline. We also found the empathy-oxytocin response was stronger in women than in men. Higher levels of empathy were also associated with more generous monetary offers toward strangers in the ultimatum game. Our findings provide the first evidence that oxytocin is a physiologic signature for empathy and that empathy mediates generosity.

  16. Intranasal Oxytocin Normalizes Amygdala Functional Connectivity in Posttraumatic Stress Disorder

    NARCIS (Netherlands)

    Koch, Saskia B. J.; van Zuiden, Mirjam; Nawijn, Laura; Frijling, Jessie L.; Veltman, Dick J.; Olff, Miranda

    2016-01-01

    The neuropeptide oxytocin (OT) has been suggested as a promising pharmacological agent for medication-enhanced psychotherapy in posttraumatic stress disorder (PTSD) because of its anxiolytic and prosocial properties. We therefore investigated the behavioral and neurobiological effects of a single

  17. Oxytocin use in South Africa — a review

    African Journals Online (AJOL)

    Nicky

    2005-06-28

    Jun 28, 2005 ... The aim of this study was to examine the use of oxytocin by obstetricians ... Use with grand multipara ... Labour is induced when delivery will benefit the health of ..... intensive nursing. ... No one used auscultation exclusively in.

  18. Oxytocin and the Biopsychology of Performance in Team Sports

    Directory of Open Access Journals (Sweden)

    Gert-Jan Pepping

    2012-01-01

    Full Text Available Little is known about the biopsychological underpinnings of expert performance in team sports. In this paper we show that there is a vast support for oxytocin as a neuropeptide involved in the encouragement of important processes linked to greater team performance in sport. We argue that oxytocin is related to biopsychological processes aimed at convergence of emotions and moods between people, and in doing so it is a critical neuropeptide involved in the shaping of important team processes in sport such as trust, generosity, altruism, cohesion, cooperation, and social motivation, and also envy and gloating. Future research should examine the role of oxytocin in these essential components of sport performance. In particular, the link between oxytocin, emotional contagion and the cultivation of experiences of positive emotions is a worthwhile line of investigation for sport participation and development as well as high performance in sport.

  19. Association of glucocorticoid and type 1 corticotropin-releasing hormone receptors gene variants and risk for depression during pregnancy and post-partum.

    Science.gov (United States)

    Engineer, Neelam; Darwin, Lucy; Nishigandh, Deole; Ngianga-Bakwin, Kandala; Smith, Steve C; Grammatopoulos, Dimitris K

    2013-09-01

    Women with postnatal depression (PND) appear to have abnormal hypothalamic pituitary adrenal (HPA) axis responses to stress, which might involve a genetic variability component. We investigated association of genetic variants in the glucocorticoid receptor (GR, NR3C1) and corticotropin releasing hormone receptor 1 (CRHR1) genes with increased risk for PND. Two hundred pregnant women were recruited prospectively and PND risk was assessed by the Edinburgh Postnatal Depression Scale (EPDS) during pregnancy and again 2-8 weeks post-natally (CW-GAPND study). The BclI and ER22/23EK single nucleotide polymorphisms (SNPs) of the GR and the haplotype-tagged rs1876828, rs242939 and rs242941 SNPs of the CRHR1 associated with genetic risk to depressive disorders were genotyped. A cut-off score of 10 was used to detect increased risk of PND. Association analysis was carried out in 140 patients that completed the study protocol. The BclI and rs242939 SNPs were over-represented in women with postnatal EPDS score ≥10 with significant allele association (p = 0.011 and depression during pregnancy and postpartum. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Hormone action. Part I. Peptide hormones

    International Nuclear Information System (INIS)

    Birnbaumer, L.; O'Malley, B.W.

    1985-01-01

    The major sections of this book on the hormonal action of peptide hormones cover receptor assays, identification of receptor proteins, methods for identification of internalized hormones and hormone receptors, preparation of hormonally responsive cells and cell hybrids, purification of membrane receptors and related techniques, assays of hormonal effects and related functions, and antibodies in hormone action

  1. Gender differences in oxytocin-associated disruption of decision bias during emotion perception.

    Science.gov (United States)

    Lynn, Spencer K; Hoge, Elizabeth A; Fischer, Laura E; Barrett, Lisa Feldman; Simon, Naomi M

    2014-09-30

    Oxytocin is associated with differences in the perception of and response to socially mediated information, such as facial expressions. Across studies, however, oxytocin׳s effect on emotion perception has been inconsistent. Outside the laboratory, emotion perception involves interpretation of perceptual uncertainty and assessment of behavioral risk. An account of these factors is largely missing from studies of oxytocin׳s effect on emotion perception and might explain inconsistent results across studies. Of relevance, studies of oxytocin׳s effect on learning and decision-making indicate that oxytocin attenuates risk aversion. We used the probability of encountering angry faces and the cost of misidentifying them as not angry to create a risky environment wherein bias to categorize faces as angry would maximize point earnings. Consistent with an underestimation of the factors creating risk (i.e., encounter rate and cost), men given oxytocin exhibited a worse (i.e., less liberal) response bias than men given placebo. Oxytocin did not influence women׳s performance. These results suggest that oxytocin may impair men׳s ability to adapt to changes in risk and uncertainty when introduced to novel or changing social environments. Because oxytocin also influences behavior in non-social realms, oxytocin pharmacotherapy could have unintended consequences (i.e., risk-prone decision-making) while nonetheless normalizing pathological social interaction. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Oxytocin and the Biopsychology of Performance in Team Sports

    OpenAIRE

    Pepping, Gert-Jan; Timmermans, Erik J.

    2012-01-01

    Little is known about the biopsychological underpinnings of expert performance in team sports. In this paper we show that there is a vast support for oxytocin as a neuropeptide involved in the encouragement of important processes linked to greater team performance in sport. We argue that oxytocin is related to biopsychological processes aimed at convergence of emotions and moods between people, and in doing so it is a critical neuropeptide involved in the shaping of important team processes i...

  3. Sex, Receptors and Attachment: A Review of Individual Factors Influencing Response to Oxytocin

    Directory of Open Access Journals (Sweden)

    Kai S Macdonald

    2013-01-01

    Full Text Available As discussed in the larger review in this special issue (MacDonald and Feifel, intranasal oxytocin (IN OT is demonstrating a growing potential as a therapeutic agent in psychiatry. Importantly, research suggests that a variety of individual factors may influence a person’s response to OT. In this mini-review, I provides a review of three: (1 sex and hormonal status; (2 genetic variation in aspects of the OT system (i.e. OT receptors; and (3 attachment history. Each of these factors will be important to monitor as we strive to develop a richer understanding of OT's role in human development, brain-based disease, and the potential for individualized, OT-targeted treatments.

  4. Labor stimulation with oxytocin: effects on obstetrical and neonatal outcomes

    Directory of Open Access Journals (Sweden)

    Pedro Hidalgo-Lopezosa

    Full Text Available Abstract Objective: to evaluate the effects of labor stimulation with oxytocin on maternal and neonatal outcomes. Method: descriptive and analytical study with 338 women who gave birth at a tertiary hospital. Obstetric and neonatal variables were measured and compared in women submitted and non-submitted to stimulation with oxytocin. Statistics were performed using Chi-square test, Fisher exact test, Student t-test; and crude Odds Ratio with 95% confidence interval were calculated. A p < 0.05 was considered statistically significant. Results: stimulation with oxytocin increases the rates of cesarean sections, epidural anesthesia and intrapartum maternal fever in primiparous and multiparous women. It has also been associated with low pH values of umbilical cord blood and with a shorter duration of the first stage of labor in primiparous women. However, it did not affect the rates of 3rd and 4th degree perineal lacerations, episiotomies, advanced neonatal resuscitation, 5-minute Apgar scores and meconium. Conclusion: stimulation with oxytocin should not be used systematically, but only in specific cases. These findings provide further evidence to health professionals and midwives on the use of oxytocin during labor. Under normal conditions, women should be informed of the possible effects of labor stimulation with oxytocin.

  5. Effects of Exogenous Oxytocin on Embryonic Survival in Cows

    Directory of Open Access Journals (Sweden)

    A. Yildiz

    2006-01-01

    Full Text Available The aim of this study was to evaluate the effect of oxytocin on embryonic survival in dairy cows. Pregnancy was verified using the early pregnancy factor (EPF activity on Day 4 after artificial insemination (AI. Pregnant cows were randomly allotted to two groups: treated (n = 8 and control (n = 8. Oxytocin (100 IU, 5 ml, DIF Turkey was administered twice daily by intravenous injections to treated cows and sterile saline (5 ml to control cows immediately before milking on days 4 to 7 after AI. Blood samples were taken via jugular vein every day from day 4 to 8 and every other day until Day 20 following insemination to evaluate the effect of oxytocin on embryonic survival. The embryonic loss was diagnosed in 3 of the 8 cows treated with oxytocin, and embryonic survival rate was 62.5% in this group versus 87.5% in controls. Short cycles occurred in 37.5% of oxytocin-treated cows. At the same time their serum progesterone concentrations rose more slowly than in controls. It was concluded that cows administered oxytocin on days 4 to 7 after insemination are at a higher risk of pregnancy loss.

  6. Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial.

    Science.gov (United States)

    Kosaka, H; Okamoto, Y; Munesue, T; Yamasue, H; Inohara, K; Fujioka, T; Anme, T; Orisaka, M; Ishitobi, M; Jung, M; Fujisawa, T X; Tanaka, S; Arai, S; Asano, M; Saito, D N; Sadato, N; Tomoda, A; Omori, M; Sato, M; Okazawa, H; Higashida, H; Wada, Y

    2016-08-23

    Recent studies have suggested that long-term oxytocin administration can alleviate the symptoms of autism spectrum disorder (ASD); however, factors influencing its efficacy are still unclear. We conducted a single-center phase 2, pilot, randomized, double-blind, placebo-controlled, parallel-group, clinical trial in young adults with high-functioning ASD, to determine whether oxytocin dosage and genetic background of the oxytocin receptor affects oxytocin efficacy. This trial consisted of double-blind (12 weeks), open-label (12 weeks) and follow-up phases (8 weeks). To examine dose dependency, 60 participants were randomly assigned to high-dose (32 IU per day) or low-dose intranasal oxytocin (16 IU per day), or placebo groups during the double-blind phase. Next, we measured single-nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (OXTR). In the intention-to-treat population, no outcomes were improved after oxytocin administration. However, in male participants, Clinical Global Impression-Improvement (CGI-I) scores in the high-dose group, but not the low-dose group, were significantly higher than in the placebo group. Furthermore, we examined whether oxytocin efficacy, reflected in the CGI-I scores, is influenced by estimated daily dosage and OXTR polymorphisms in male participants. We found that >21 IU per day oxytocin was more effective than ⩽21 IU per day, and that a SNP in OXTR (rs6791619) predicted CGI-I scores for ⩽21 IU per day oxytocin treatment. No severe adverse events occurred. These results suggest that efficacy of long-term oxytocin administration in young men with high-functioning ASD depends on the oxytocin dosage and genetic background of the oxytocin receptor, which contributes to the effectiveness of oxytocin treatment of ASD.

  7. Randomised controlled trial of oxytocin alone versus oxytocin and ergometrine in active management of third stage of labour.

    OpenAIRE

    McDonald, S J; Prendiville, W J; Blair, E

    1993-01-01

    OBJECTIVE--To compare intramuscular oxytocin alone and intramuscular oxytocin with ergometrine (Syntometrine) for their effect in reducing the risk of postpartum haemorrhage when both are used as part of the active management of the third stage of labour. DESIGN--Double blind, randomised controlled trial. SETTING--Two metropolitan teaching hospitals in Perth, Western Australia. SUBJECTS--All women who expected a vaginal birth during the period of the trial. Informed consent was obtained. MAIN...

  8. Anxiolytic-like effect of oxytocin in the simulated public speaking test.

    Science.gov (United States)

    de Oliveira, Danielle C G; Zuardi, Antonio W; Graeff, Frederico G; Queiroz, Regina H C; Crippa, José A S

    2012-04-01

    Oxytocin (OT) is known to be involved in anxiety, as well as cardiovascular and hormonal regulation. The objective of this study was to assess the acute effect of intranasally administered OT on subjective states, as well as cardiovascular and endocrine parameters, in healthy volunteers (n = 14) performing a simulated public speaking test. OT or placebo was administered intranasally 50 min before the test. Assessments were made across time during the experimental session: (1) baseline (-30 min); (2) pre-test (-15 min); (3) anticipation of the speech (50 min); (4) during the speech (1:03 h), post-test time 1 (1:26 h), and post-test time 2 (1:46 h). Subjective states were evaluated by self-assessment scales. Cortisol serum and plasma adrenocorticotropic hormone (ACTH) were measured. Additionally, heart rate, blood pressure, skin conductance, and the number of spontaneous fluctuations in skin conductance were measured. Compared with placebo, OT reduced the Visual Analogue Mood Scale (VAMS) anxiety index during the pre-test phase only, while increasing sedation at the pre-test, anticipation, and speech phases. OT also lowered the skin conductance level at the pre-test, anticipation, speech, and post-test 2 phases. Other parameters evaluated were not significantly affected by OT. The present results show that OT reduces anticipatory anxiety, but does not affect public speaking fear, suggesting that this hormone has anxiolytic properties.

  9. Correlation between oxytocin neuronal sensitivity and oxytocin receptor binding: An electrophysiological and autoradiographical study comparing rat and guinea pig hippocampus

    International Nuclear Information System (INIS)

    Raggenbass, M.; Tribollet, E.; Dubois-Dauphin, M.; Dreifuss, J.J.

    1989-01-01

    In transverse hippocampal slices from rat and guinea pig brains, the authors obtained unitary extracellular recordings from nonpyramidal neurones located in or near the stratum pyramidale in the CA1 field and in the transition region between the CA1 and the subiculum. In rats, these neurones responded to oxytocin at 50-1,000 nM by a reversible increase in firing rate. The oxytocin-induced excitation was suppressed by a synthetic structural analogue that acts as a potent, selective antioxytocic on peripheral receptors. Nonpyramidal neurones were also excited by carbachol at 0.5-10 μM. The effect of this compound was postsynaptic and was blocked by the muscarinic antagonist atropine. In guinea pigs, by contrast, nonpyramidal neurones were unaffected by oxytocin, although they were excited by carbachol. Light microscopic autoradiography, carried out using a radioiodinated selective antioxytocic as a ligand, revealed labeling in the subiculum and in the CA1 area of the hippocampus of rats, whereas no oxytocin-binding sites were detected in the hippocampus of guinea pigs. The results indicate (i) that a hippocampal action of oxytocin is species-dependent and (ii) that a positive correlation exists between neuronal responsiveness to oxytocin and the presence in the hippocampus of high-affinity binding sites for this peptide

  10. Physicians' subjectivity in evaluating oxytocin challenge tests.

    Science.gov (United States)

    Peck, T M

    1980-07-01

    Five physicians subspecializing in maternal-fetal medicine individually evaluated 50 oxytocin challenge tests (OCTs), of which 33 were originally read as positive. There was considerable disagreement among the study physicians (SPs) such that 2 SPs would agree, on the average, only 52% of the time on any one OCT. The SPs were also asked to evaluate fetal heart rate (FHR) reactivity patterns, if present. Again, there was great disagreement. When the majority (3 of 5 or more) of SPs agreed on the OCT result and/or reactivity, there was reasonable correlation with neonatal outcome, indicating the validity of the physiologic premise of the test. In particular, the presence or absence of FHR accelerations with fetal motion, regardless of the OCT reading, correlated extremely well with eventual neonatal outcome. This indicates that the most significant variable in antepartum FHR monitoring is the FHR acceleration pattern.

  11. The radioimmunoassay of plasma oxytocin in pregnancy and at parturition

    International Nuclear Information System (INIS)

    Kogure, Satohisa

    1976-01-01

    The titer of the antiserum obtained by inoculating oxytocin-bovine serum albumin antigen into mature male rabbits was 1:64,000 in the final dilution, and the rate of conjugation with labeled-oxytocin was 34%. The cross reaction rate of the antiserum was 0.01% or below, both for lysine vasopressin and arginine vasopressin. The sensitivity of the radioimmunoassay using this antiserum was 5μIU. When a known quantity of oxytocin was added to plasma for measurement, the mean recovery rate was about 93%. The blood oxytocin concentration was 6.1+-2.5μIU/ml (ml omitted hereafter) in the early stage of pregnancy, 12.5+-6.0μIU in the middle stage, and 27.0+-7.5μIU in the terminal stage. The oxytocin concentration in the maternal blood was 34.1+-4.9μIU in the second stage, the concentration in the umbilical arterial blood immediately after delivery 3.5+-5.3μIU, and that in the umbilical venous blood 30.0+-4.2μIU. In cases of caesarean section not in labor, the oxytocin concentration in the maternal blood was 27.1+-6.6μIU, that in the umbilical arterial blood 25.1+-5.4μIU, and that in the umbilical venous blood 25.4+-5.4μIU. In cases of caesarean section in labor, the oxytocin concentration in the maternal blood was 37.1+-7.1μIU, that in the umbilical arterial blood 31.4+-6.7μIU, and that in the umbilical venous blood 27.0+-7.8μIU. The half-life of the oxytocin in the peripheral blood in cases injected with oxytocin was 5-10 minutes. When prostaglandin F2α was administered intravenously, the oxytocin concentration in the peripheral blood was increased in cases in labor. (Chiba, N.)

  12. Plasma oxytocin during third stage of labour: comparison of natural and active management.

    OpenAIRE

    Thornton, S.; Davison, J. M.; Baylis, P. H.

    1988-01-01

    The incidences of postpartum haemorrhage and retained placenta have decreased with the use of synthetic oxytocin and controlled cord traction. Whether such treatment is valuable is open to question because of the lack of clinical and physiological studies. The physiological effects of synthetic oxytocin on plasma concentrations of oxytocin and events during delivery were assessed. Plasma oxytocin concentration was determined in serial samples during the late second stage and throughout the th...

  13. Oxytocin Differentially Affects Sucrose Taking and Seeking in Male and Female Rats

    OpenAIRE

    Zhou, Luyi; Ghee, Shannon M.; See, Ronald E.; Reichel, Carmela M.

    2015-01-01

    Oxytocin has a modulatory role in natural and drug reward processes. While the role of oxytocin in pair bonding and reproduction has been extensively studied, sex differences in conditioned and unconditioned behavioral responses to oxytocin treatment have not been fully characterized. Here, we determined whether male and female rats would show similar dose response curves in response to acute oxytocin on measures of locomotor activity, sucrose seeking, and sucrose intake. Male and freely cycl...

  14. Oxytocin decreases sweet taste sensitivity in mice.

    Science.gov (United States)

    Sinclair, Michael S; Perea-Martinez, Isabel; Abouyared, Marianne; St John, Steven J; Chaudhari, Nirupa

    2015-03-15

    Oxytocin (OXT) suppresses food intake and lack of OXT leads to overconsumption of sucrose. Taste bud cells were recently discovered to express OXT-receptor. In the present study we tested whether administering OXT to wild-type mice affects their licking behavior for tastants in a paradigm designed to be sensitive to taste perception. We injected C57BL/6J mice intraperitoneally (i.p.) with 10mg/kg OXT and assayed their brief-access lick responses, motivated by water deprivation, to NaCl (300mM), citric acid (20mM), quinine (0.3mM), saccharin (10mM), and a mix of MSG and IMP (100mM and 0.5mM respectively). OXT had no effect on licking for NaCl, citric acid, or quinine. A possible effect of OXT on saccharin and MSG+IMP was difficult to interpret due to unexpectedly low lick rates to water (the vehicle for all taste solutions), likely caused by the use of a high OXT dose that suppressed licking and other behaviors. A subsequent experiment focused on another preferred tastant, sucrose, and employed a much lower OXT dose (0.1mg/kg). This modification, based on our measurements of plasma OXT following i.p. injection, permitted us to elevate plasma [OXT] sufficiently to preferentially activate taste bud cells. OXT at this low dose significantly reduced licking responses to 0.3M sucrose, and overall shifted the sucrose concentration - behavioral response curves rightward (mean EC50saline=0.362M vs. EC50OXT=0.466M). Males did not differ from females under any condition in this study. We propose that circulating oxytocin is another factor that modulates taste-based behavior. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Effects of sex, menstrual cycle phase, and endogenous hormones on cognition in schizophrenia.

    Science.gov (United States)

    Rubin, Leah H; Carter, C Sue; Drogos, Lauren L; Pournajafi-Nazarloo, Hossein; Sweeney, John A; Maki, Pauline M

    2015-08-01

    In women with schizophrenia, cognition has been shown to be enhanced following administration of hormone therapy or oxytocin. We examined how natural hormonal changes across the menstrual cycle influence cognition in women with schizophrenia. We hypothesized that female patients would perform worse on "female-dominant" tasks (verbal memory/fluency) and better on "male-dominant" tasks (visuospatial) during the early follicular phase (low estradiol and progesterone) compared to midluteal phase (high estradiol and progesterone) in relation to estradiol but not progesterone. Fifty-four women (23 with schizophrenia) completed cognitive assessments and provided blood for sex steroid assays and oxytocin at early follicular (days 2-4) and midluteal (days 20-22) phases. Men were included to verify the expected pattern of sex differences on cognitive tests. Expected sex differences were observed on "female-dominant" and "male-dominant" tasks (pperformance did not change across the menstrual cycle on "female-dominant" or "male-dominant" tasks in either group. Estradiol and progesterone levels were unrelated to cognitive performance. Oxytocin levels did not change across the menstrual cycle but were positively related to performance on "female-dominant" tasks in female patients only (pperformance on female dominant tests in women. Physiological levels of oxytocin may thus have a more powerful benefit in some cognitive domains than estrogens in schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Oxytocin differentially affects sucrose taking and seeking in male and female rats.

    Science.gov (United States)

    Zhou, Luyi; Ghee, Shannon M; See, Ronald E; Reichel, Carmela M

    2015-04-15

    Oxytocin has a modulatory role in natural and drug reward processes. While the role of oxytocin in pair bonding and reproduction has been extensively studied, sex differences in conditioned and unconditioned behavioral responses to oxytocin treatment have not been fully characterized. Here, we determined whether male and female rats would show similar dose response curves in response to acute oxytocin on measures of locomotor activity, sucrose seeking, and sucrose intake. Male and freely cycling female rats received vehicle or oxytocin (0.1, 0.3, 1, 3mg/kg, IP) injections before behavioral tests designed to assess general motor activity, as well as sucrose self-administration and seeking. Lower doses of oxytocin decreased motor activity in a novel environment in females relative to males. Likewise, lower doses of oxytocin in females decreased responding for sucrose during maintenance of sucrose self-administration and reinstatement to sucrose-conditioned cues. However, sucrose seeking in response to a sucrose prime was only decreased by the highest oxytocin dose in both sexes. In general, oxytocin had similar effects in both sexes. However, females were more sensitive to lower doses of oxytocin than males. These findings are consistent with the notion that oxytocin regulates many of the same behaviors in males and females, but that the effects are typically more profound in females. Therapeutic use of oxytocin should include sex as a factor in determining dose regimens. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Aspartate buffer and divalent metal ions affect oxytocin in aqueous solution and protect it from degradation

    DEFF Research Database (Denmark)

    Avanti, Christina; Oktaviani, Nur Alia; Hinrichs, Wouther L.J.

    2013-01-01

    Oxytocin is a peptide drug used to induce labor and prevent bleeding after childbirth. Due to its instability, transport and storage of oxytocin formulations under tropical conditions is problematic. In a previous study, we have found that the stability of oxytocin in aspartate buffered formulati...

  18. Oxytocin effects on complex brain networks are moderated by experiences of maternal love withdrawal

    NARCIS (Netherlands)

    Riem, M.M.E.; van IJzendoorn, M.H.; Tops, M.; Boksem, M.A.S.; Rombouts, S.A.R.B.; Bakermans-Kranenburg, M.J.

    2013-01-01

    The neuropeptide oxytocin has been implicated in a variety of social processes. However, recent studies indicate that oxytocin does not enhance prosocial behavior in all people in all circumstances. Here, we investigate effects of intranasal oxytocin administration on intrinsic functional brain

  19. Aspartate buffer and divalent metal ions affect oxytocin in aqueous solution and protect it from degradation

    NARCIS (Netherlands)

    Avanti, Christina; Oktaviani, Nur Alia; Hinrichs, Wouter L J; Frijlink, Henderik W; Mulder, Frans A A

    2013-01-01

    Oxytocin is a peptide drug used to induce labor and prevent bleeding after childbirth. Due to its instability, transport and storage of oxytocin formulations under tropical conditions is problematic. In a previous study, we have found that the stability of oxytocin in aspartate buffered formulation

  20. Hormone Data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Hormones quantified from marine mammal and sea turtle tissue provide information about the status of each animal sampled, including its sex, reproductive status and...

  1. Hormone Therapy

    Science.gov (United States)

    ... it also can be a sign of endometrial cancer. All bleeding after menopause should be evaluated. Other side effects reported by women who take hormone therapy include fluid retention and breast soreness. This soreness usually lasts for a short ...

  2. Increased Serum and Urinary Oxytocin Concentrations after Nasal Administration in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Andrea Temesi

    2017-09-01

    Full Text Available In recent years more and more studies have revealed the effect of extraneous oxytocin on the social behavior of dogs. The distribution of administered oxytocin in different physiologically relevant compartments is important because this knowledge forms the basis for the timing of behavior tests after the administration. Most behavioral studies rely on the non-invasive intranasal application of oxytocin. The aim of this study was to determine the time course of intranasal administered oxytocin secretion into blood and urine and also establish a connection between intranasal received oxytocin and urinary cortisol in dogs. In our experiment, four dogs received three puffs, 12 IU intranasal oxytocin treatment, two dogs received three puffs intranasal placebo treatment. Blood and urine samples were collected immediately prior to the administration then regularly during 4 h. After nasal oxytocin application, the serum oxytocin concentration increased, reached a maximum 15 min after the treatment and then rapidly returned to baseline levels 45 min later. The peak urinary oxytocin concentration occurred between 45 and 60 min after administration and returned to baseline levels slowly. We found considerable differences among individuals in the secretion of oxytocin in both the serum and the urinary oxytocin concentration measurements. Our results confirm that intranasally administered oxytocin passes into the blood stream. The time course of intranasally administered oxytocin secretion is similar to the time course of intravenously administered oxytocin secretion, and the peak values are also similar in both the serum and the urinary oxytocin concentration measurements, although there are large individual differences.

  3. On the role of oxytocin in borderline personality disorder.

    Science.gov (United States)

    Brüne, Martin

    2016-09-01

    Interpersonal dysfunction is central to borderline personality disorder (BPD). Recent research has focused on the role of oxytocin (OT) in BPD, particularly regarding associations of OT activity with symptoms, genetic polymorphisms of the oxytocin receptor coding gene (OXTR) in BPD, and experimental modification of interpersonal core problems of patients with BPD such as hypervigilance towards threat detection, mistrust, and non-verbal behaviour during social interaction by intranasal application of OT. A literature ('medline') review was performed using the keywords 'oxytocin' and 'borderline personality disorder'. Secondary literature on trauma and attachment in relation to OT was also considered relevant. Together, findings suggest that in BPD OT is associated with enhanced defensive mechanisms and avoidance behaviour. Moreover, gene-environment interaction concerning polymorphic variations of the OXTR gene and childhood adversity in BPD suggests that these genes convey developmental flexibility or 'differential susceptibility' to environmental contingencies, whereby BPD resides at the poor outcome end of the spectrum. In view of the conflicting literature, it needs to be studied carefully whether OT can serve as a therapeutic agent given adjunct to psychotherapy in BPD. More research about the role of OT is also required with regard to the prevention of the non-genetic intergenerational transmission of BPD. Clarifying the role of OT in BPD may also benefit from research in non-human animals targeting the interaction between early adversity and OT availability more directly. The study of oxytocin can contribute to the understanding of the neurobiology of borderline personality disorder. Oxytocin is critically involved in attachment security, and methylation of the oxytocin receptor may play a role in the epigenetic modulation of early adversity. The intranasal application of oxytocin may be a useful therapeutic adjunct to psychotherapy. Insecure attachment and

  4. Emotion recognition and oxytocin in patients with schizophrenia

    Science.gov (United States)

    Averbeck, B. B.; Bobin, T.; Evans, S.; Shergill, S. S.

    2012-01-01

    Background Studies have suggested that patients with schizophrenia are impaired at recognizing emotions. Recently, it has been shown that the neuropeptide oxytocin can have beneficial effects on social behaviors. Method To examine emotion recognition deficits in patients and see whether oxytocin could improve these deficits, we carried out two experiments. In the first experiment we recruited 30 patients with schizophrenia and 29 age- and IQ-matched control subjects, and gave them an emotion recognition task. Following this, we carried out a second experiment in which we recruited 21 patients with schizophrenia for a double-blind, placebo-controlled cross-over study of the effects of oxytocin on the same emotion recognition task. Results In the first experiment we found that patients with schizophrenia had a deficit relative to controls in recognizing emotions. In the second experiment we found that administration of oxytocin improved the ability of patients to recognize emotions. The improvement was consistent and occurred for most emotions, and was present whether patients were identifying morphed or non-morphed faces. Conclusions These data add to a growing literature showing beneficial effects of oxytocin on social–behavioral tasks, as well as clinical symptoms. PMID:21835090

  5. Oxytocin receptor gene variation predicts subjective responses to MDMA.

    Science.gov (United States)

    Bershad, Anya K; Weafer, Jessica J; Kirkpatrick, Matthew G; Wardle, Margaret C; Miller, Melissa A; de Wit, Harriet

    2016-12-01

    3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") enhances desire to socialize and feelings of empathy, which are thought to be related to increased oxytocin levels. Thus, variation in the oxytocin receptor gene (OXTR) may influence responses to the drug. Here, we examined the influence of a single OXTR nucleotide polymorphism (SNP) on responses to MDMA in humans. Based on findings that carriers of the A allele at rs53576 exhibit reduced sensitivity to oxytocin-induced social behavior, we hypothesized that these individuals would show reduced subjective responses to MDMA, including sociability. In this three-session, double blind, within-subjects study, healthy volunteers with past MDMA experience (N = 68) received a MDMA (0, 0.75 mg/kg, and 1.5 mg/kg) and provided self-report ratings of sociability, anxiety, and drug effects. These responses were examined in relation to rs53576. MDMA (1.5 mg/kg) did not increase sociability in individuals with the A/A genotype as it did in G allele carriers. The genotypic groups did not differ in responses at the lower MDMA dose, or in cardiovascular or other subjective responses. These findings are consistent with the idea that MDMA-induced sociability is mediated by oxytocin, and that variation in the oxytocin receptor gene may influence responses to the drug.

  6. Intranasal administration of oxytocin increases envy and schadenfreude (gloating).

    Science.gov (United States)

    Shamay-Tsoory, Simone G; Fischer, Meytal; Dvash, Jonathan; Harari, Hagai; Perach-Bloom, Nufar; Levkovitz, Yechiel

    2009-11-01

    Humans have a strong social tendency to compare themselves with others. We tend to feel envious when we receive less valuable rewards and may rejoice when our payoffs are more advantageous. Envy and schadenfreude (gloating over the other's misfortune) are social emotions widely agreed to be a symptom of the human social tendency to compare one's payoffs with those of others. Given the important social components of envy and gloating, we speculated that oxytocin may have a modulating effect on the intensity of these emotions. Fifty-six participants participated in this double-blind, placebo-controlled, within-subject study. Following the administration of oxytocin or a placebo, participants played a game of chance with another (fake) participant who either won more money (envy manipulation), lost more money (schadenfreude manipulation), or won/lost equal amounts of money. In comparison with the placebo, oxytocin increased the envy ratings during unequal monetary gain conditions involving relative loss (when the participant gained less money than another player). Oxytocin also increased the ratings of gloating during relative gain conditions (when the participant gained more money than the other player). By contrast, oxytocin had no effect on the emotional ratings following equal monetary gains nor did it affect general mood ratings. These results suggest that the oxytocinergic system is involved in modulating envy and gloating. Thus, contrary to the prevailing belief that this system is involved solely in positive prosocial behaviors, it probably plays a key role in a wider range of social emotion-related behaviors.

  7. The influence of oxytocin on interpersonal rhythmic synchronization and social bonding

    DEFF Research Database (Denmark)

    Gebauer, Line; Witek, Maria; Hansen, Niels Chr.

    oxytocin. In this study we investigated the role of oxytocin on interpersonal rhythmic synchronization, and its relation to pro-social effects, using an interactive finger tapping setup. Pairs of two tapped together, and both participants in each pair received either oxytocin or a non-active placebo...... as nasal spray. Our preliminary analyses showed trends in which intranasally administered oxytocin improved interpersonal synchronization. In this poster we present the full data set and analysis of the effect of oxytocin on interpersonal synchronization and social bonding....

  8. Social evolution. Oxytocin-gaze positive loop and the coevolution of human-dog bonds.

    Science.gov (United States)

    Nagasawa, Miho; Mitsui, Shouhei; En, Shiori; Ohtani, Nobuyo; Ohta, Mitsuaki; Sakuma, Yasuo; Onaka, Tatsushi; Mogi, Kazutaka; Kikusui, Takefumi

    2015-04-17

    Human-like modes of communication, including mutual gaze, in dogs may have been acquired during domestication with humans. We show that gazing behavior from dogs, but not wolves, increased urinary oxytocin concentrations in owners, which consequently facilitated owners' affiliation and increased oxytocin concentration in dogs. Further, nasally administered oxytocin increased gazing behavior in dogs, which in turn increased urinary oxytocin concentrations in owners. These findings support the existence of an interspecies oxytocin-mediated positive loop facilitated and modulated by gazing, which may have supported the coevolution of human-dog bonding by engaging common modes of communicating social attachment. Copyright © 2015, American Association for the Advancement of Science.

  9. Characterization of the oxytocin system regulating affiliative behavior in female prairie voles.

    Science.gov (United States)

    Ross, H E; Cole, C D; Smith, Y; Neumann, I D; Landgraf, R; Murphy, A Z; Young, L J

    2009-09-15

    Oxytocin regulates partner preference formation and alloparental behavior in the socially monogamous prairie vole (Microtus ochrogaster) by activating oxytocin receptors in the nucleus accumbens of females. Mating facilitates partner preference formation, and oxytocin-immunoreactive fibers in the nucleus accumbens have been described in prairie voles. However, there has been no direct evidence of oxytocin release in the nucleus accumbens during sociosexual interactions, and the origin of the oxytocin fibers is unknown. Here we show for the first time that extracellular concentrations of oxytocin are increased in the nucleus accumbens of female prairie vole during unrestricted interactions with a male. We further show that the distribution of oxytocin-immunoreactive fibers in the nucleus accumbens is conserved in voles, mice and rats, despite remarkable species differences in oxytocin receptor binding in the region. Using a combination of site-specific and peripheral infusions of the retrograde tracer Fluorogold, we demonstrate that the nucleus accumbens oxytocin-immunoreactive fibers likely originate from paraventricular and supraoptic hypothalamic neurons. This distribution of retrogradely labeled neurons is consistent with the hypothesis that striatal oxytocin fibers arise from collaterals of magnocellular neurons of the neurohypophysial system. If correct, this may serve to coordinate peripheral and central release of oxytocin with appropriate behavioral responses associated with reproduction, including pair bonding after mating, and maternal responsiveness following parturition and during lactation.

  10. Targeting the Oxytocin System to Treat Addictive Disorders: Rationale and Progress to Date

    Science.gov (United States)

    Lee, Mary R.; Rohn, Matthew C.H.; Tanda, Gianluigi; Leggio, Lorenzo

    2016-01-01

    The neuropeptide oxytocin plays a role in reward, stress, social affiliation, learning and memory processes. As such there is increasing interest in oxytocin as a potential treatment for addictions. The oxytocin system is itself altered by acute or chronic exposure to drugs of abuse. A large number of preclinical studies in rodents have investigated the effect of oxytocin on various drug-induced behaviors to determine whether oxytocin can reverse the neuroadaptations occurring with repeated drug and alcohol use. In addition, the mechanisms by which oxytocin acts to modify the behavioral response to drugs of abuse are beginning to be understood. More recently, a few small clinical studies have been conducted in cocaine, cannabis and alcohol dependence. This review summarizes the preclinical as well as clinical literature to date on the oxytocin system and its relevance to drug and alcohol addiction. PMID:26932552

  11. The role of oxytocin in familiarization-habituation responses to social novelty

    Directory of Open Access Journals (Sweden)

    Mattie eTops

    2013-10-01

    Full Text Available Stress or arousal responses to novel social contexts ease off when individuals get familiar with the social context. In the present study we investigated whether oxytocin is involved in this process of familiarization-habituation, as oxytocin is known to increase trust and decrease anxiety. Fifty-nine healthy female subjects took part in the same experimental procedure in two sessions separated by four weeks. In the first (novelty session state trust scores were significantly positively correlated with salivary oxytocin levels, while in the second (familiarity session state trust scores were significantly negatively correlated with salivary oxytocin levels. In a path model, oxytocin was associated with increased trust in the novelty session and trust was associated with decreased oxytocin levels in the familiarity session. The results are consistent with the idea that oxytocin decreases stress-to-novelty responses by promoting familiarization to novel social contexts.

  12. The obesity-associated transcription factor ETV5 modulates circulating glucocorticoids

    Science.gov (United States)

    Gutierrez-Aguilar, Ruth; Thompson, Abigail; Marchand, Nathalie; Dumont, Patrick; Woods, Stephen C.; de Launoit, Yvan; Seeley, Randy J.; Ulrich-Lai, Yvonne M.

    2015-01-01

    The transcription factor E-twenty-six version 5 (ETV5) has been linked with obesity in genome-wide association studies. Moreover, ETV5-deficient mice (knockout; KO) have reduced body weight, lower fat mass, and are resistant to diet-induced obesity, directly linking ETV5 to the regulation of energy balance and metabolism. ETV5 is expressed in hypothalamic brain regions that regulate both metabolism and HPA axis activity, suggesting that ETV5 may also modulate HPA axis function. In order to test this possibility, plasma corticosterone levels were measured in ETV5 KO and wildtype (WT) mice before (pre-stress) and after (post-stress) a mild stressor (intraperitoneal injection). ETV5 deficiency increased both pre- and post-stress plasma corticosterone, suggesting that loss of ETV5 elevated glucocorticoid tone. Consistent with this idea, ETV5 KO mice have reduced thymus weight, suggestive of increased glucocorticoid-induced thymic involution. ETV5 deficiency also decreased the mRNA expression of glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and vasopressin receptor 1A in the hypothalamus, without altering vasopressin, corticotropin-releasing hormone, or oxytocin mRNA expression. In order to test whether reduced MR and GR expression affected glucocorticoid negative feedback, a dexamethasone suppression test was performed. Dexamethasone reduced plasma corticosterone in both ETV5 KO and WT mice, suggesting that glucocorticoid negative feedback was unaltered by ETV5 deficiency. In summary, these data suggest that the obesity-associated transcription factor ETV5 normally acts to diminish circulating glucocorticoids. This might occur directly via ETV5 actions on HPA-regulatory brain circuitry, and/or indirectly via ETV5-induced alterations in metabolic factors that then influence the HPA axis. PMID:25813907

  13. Sex differences in associations of arginine vasopressin and oxytocin with resting-state functional brain connectivity.

    Science.gov (United States)

    Rubin, Leah H; Yao, Li; Keedy, Sarah K; Reilly, James L; Bishop, Jeffrey R; Carter, C Sue; Pournajafi-Nazarloo, Hossein; Drogos, Lauren L; Tamminga, Carol A; Pearlson, Godfrey D; Keshavan, Matcheri S; Clementz, Brett A; Hill, Scot K; Liao, Wei; Ji, Gong-Jun; Lui, Su; Sweeney, John A

    2017-01-02

    Oxytocin (OT) and arginine vasopressin (AVP) exert robust and sexually dimorphic influences on cognition and emotion. How these hormones regulate relevant functional brain systems is not well understood. OT and AVP serum concentrations were assayed in 60 healthy individuals (36 women). Brain functional networks assessed with resting-state functional magnetic resonance imaging (rs-fMRI) were constructed with graph theory-based approaches that characterize brain networks as connected nodes. Sex differences were demonstrated in rs-fMRI. Men showed higher nodal degree (connectedness) and efficiency (information propagation capacity) in left inferior frontal gyrus (IFG) and bilateral superior temporal gyrus (STG) and higher nodal degree in left rolandic operculum. Women showed higher nodal betweenness (being part of paths between nodes) in right putamen and left inferior parietal gyrus (IPG). Higher hormone levels were associated with less intrinsic connectivity. In men, higher AVP was associated with lower nodal degree and efficiency in left IFG (pars orbitalis) and left STG and less efficiency in left IFG (pars triangularis). In women, higher AVP was associated with lower betweenness in left IPG, and higher OT was associated with lower nodal degree in left IFG (pars orbitalis). Hormones differentially correlate with brain networks that are important for emotion processing and cognition in men and women. AVP in men and OT in women may regulate orbital frontal cortex connectivity, which is important in emotion processing. Hormone associations with STG and pars triangularis in men and parietal cortex in women may account for well-established sex differences in verbal and visuospatial abilities, respectively. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  14. Oxytocin Reduces Cocaine Cued Fos Activation in a Regionally Specific Manner

    Science.gov (United States)

    Leong, Kah-Chung; Freeman, Linnea R; Berini, Carole R; Ghee, Shannon M; See, Ronald E

    2017-01-01

    Abstract Background Oxytocin may be a possible treatment for multiple neuropsychiatric disorders, including cocaine addiction. Little is known about the site-specific effects of oxytocin on various drug addiction-related brain regions. Furthermore, sexually dimorphic effects of oxytocin on neural function in the addiction circuit have not been established. Here, we studied Fos expression following cocaine-cued reinstatement in both male and female rats. Methods Male and female rats underwent self-administration, extinction, and reinstatement tests. On test days, rats were given oxytocin or vehicle, and lever pressing was measured in response to conditioned cocaine cues. Rats were perfused and Fos staining measured in the central amygdala, medial prefrontal cortex, nucleus accumbens core, and subthalamic nucleus. Fos/oxytocin double labeling occurred in the paraventricular nucleus of the hypothalamus. Results Rats reinstated to cocaine cues relative to extinction responding and oxytocin reduced cocaine seeking. Oxytocin combined with contingent cue presentations increased Fos+ oxytocin cell bodies within the paraventricular nucleus of the hypothalamus relative to vehicle. Fos expression robustly increased in the central amygdala following oxytocin administration. Oxytocin reversed cue-induced Fos expression in the medial prefrontal cortex, nucleus accumbens core, and subthalamic nucleus. Central oxytocin infusion also attenuated reinstated cocaine seeking. Conclusions Oxytocin decreased reinstated cocaine seeking, increased Fos activation in the paraventricular nucleus of the hypothalamus and central amygdala, but normalized cue-induced Fos activation in the medial prefrontal cortex, nucleus accumbens core, and subthalamic nucleus, thereby demonstrating regionally specific activation patterns. No sex differences were seen for the effects of oxytocin on cocaine seeking and Fos activation, indicating that oxytocin acts on similar central neural circuits critical to

  15. The Neuropeptide Oxytocin Induces a Social Altruism Bias.

    Science.gov (United States)

    Marsh, Nina; Scheele, Dirk; Gerhardt, Holger; Strang, Sabrina; Enax, Laura; Weber, Bernd; Maier, Wolfgang; Hurlemann, René

    2015-11-25

    Current psychological concepts of social and ecological responsibility emphasize the relevance of altruism, suggesting that more altruistic individuals are more likely to engage in sustainable behaviors. Emerging evidence indicates a central role of the neuropeptide oxytocin in promoting altruism. Whether this influence extends to ecological responsibility or is limited to the social domain remains unknown. In two independent experiments involving 172 human participants, we addressed this question by exposing subjects to a sustainability-related monetary donation task, with the option to support either socially or ecologically framed charities. We found that oxytocin induced a context-dependent change in altruistic behavior away from pro-environmental toward pro-social donations, while keeping constant the overall proportion of donated money. This pro-social bias transcended to the domain of sustainable consumption. Collectively, our findings demonstrate that altruistic priorities vary as a function of oxytocin system activity, which has implications for the promotion of pro-environmental attitudes and eco-friendly behaviors. Individual responses to ecological and social sustainability require a shift in personal priorities away from selfish to more altruistic behaviors. Emerging evidence indicates a central role of the hypothalamic peptide oxytocin in promoting altruism, but whether the influence of oxytocin benefits altruistic decision-making in the context of ecological and social sustainability is unclear. In two independent behavioral experiments involving 172 human subjects, we show that heightened oxytocin system activity induces a social altruism bias at the cost of ecological responsibility. Our results have fundamental implications for policy interventions and business strategies designed to sustain ecological resources by suggesting that a social framing may attract more individuals to engage in pro-environmental and eco-friendly behaviors. Copyright

  16. The role of oxytocin in cardiovascular regulation

    Directory of Open Access Journals (Sweden)

    J. Gutkowska

    2014-03-01

    Full Text Available Studies of body volume expansion have indicated that lesions of the anteroventral third ventricle and median eminence block the release of atrial natriuretic peptide (ANP into the circulation. Detailed analysis of the lesions showed that activation of oxytocin (OT-ergic neurons is responsible for ANP release, and it has become clear that activation of neuronal circuitry elicits OT secretion into the circulation, activating atrial OT receptors and ANP release from the heart. Subsequently, we have uncovered the entire functional OT system in the rat and the human heart. An abundance of OT has been observed in the early development of the fetal heart, and the capacity of OT to generate cardiomyocytes (CMs has been demonstrated in various types of stem cells. OT treatment of mesenchymal stem cells stimulates paracrine factors beneficial for cardioprotection. Cardiovascular actions of OT include: i lowering blood pressure, ii negative inotropic and chronotropic effects, iii parasympathetic neuromodulation, iv vasodilatation, v anti-inflammatory activity, vi antioxidant activity, and vii metabolic effects. OT actions are mediated by nitric oxide and ANP. The beneficial actions of OT may include the increase in glucose uptake by CMs and stem cells, reduction in CM hypertrophy, oxidative stress, and mitochondrial protection of several cell types. In experimentally induced myocardial infarction in rats, continuous in vivo OT delivery improves cardiac healing and cardiac work, reduces inflammation, and stimulates angiogenesis. Because OT plays anti-inflammatory and cardioprotective roles and improves vascular and metabolic functions, it demonstrates potential for therapeutic use in various pathologic conditions.

  17. Oxytocin promotes social bonding in dogs.

    Science.gov (United States)

    Romero, Teresa; Nagasawa, Miho; Mogi, Kazutaka; Hasegawa, Toshikazu; Kikusui, Takefumi

    2014-06-24

    Recent evidence suggests that enduring social bonds have fitness benefits. However, very little is known about the neural circuitry and neurochemistry underlying the formation and maintenance of stable social bonds outside reproductive contexts. Oxytocin (OT), a neuropeptide synthetized by the hypothalamus in mammals, regulates many complex forms of social behavior and cognition in both human and nonhuman animals. Animal research, however, has concentrated on monogamous mammals, and it remains unknown whether OT also modulates social bonds in nonreproductive contexts. In this study we provide behavioral evidence that exogenous OT promotes positive social behaviors in the domestic dog toward not only conspecifics but also human partners. Specifically, when sprayed with OT, dogs showed higher social orientation and affiliation toward their owners and higher affiliation and approach behaviors toward dog partners than when sprayed with placebo. Additionally, the exchange of socio-positive behaviors with dog partners triggered the release of endogenous OT, highlighting the involvement of OT in the development of social relationships in the domestic dog. These data provide new insight into the mechanisms that facilitate the maintenance of close social bonds beyond immediate reproductive interest or genetic ties and complement a growing body of evidence that identifies OT as one of the neurochemical foundations of sociality in mammalian species.

  18. The role of oxytocin in cardiovascular regulation

    International Nuclear Information System (INIS)

    Gutkowska, J.; Jankowski, M.; Antunes-Rodrigues, J.

    2014-01-01

    Studies of body volume expansion have indicated that lesions of the anteroventral third ventricle and median eminence block the release of atrial natriuretic peptide (ANP) into the circulation. Detailed analysis of the lesions showed that activation of oxytocin (OT)-ergic neurons is responsible for ANP release, and it has become clear that activation of neuronal circuitry elicits OT secretion into the circulation, activating atrial OT receptors and ANP release from the heart. Subsequently, we have uncovered the entire functional OT system in the rat and the human heart. An abundance of OT has been observed in the early development of the fetal heart, and the capacity of OT to generate cardiomyocytes (CMs) has been demonstrated in various types of stem cells. OT treatment of mesenchymal stem cells stimulates paracrine factors beneficial for cardioprotection. Cardiovascular actions of OT include: i) lowering blood pressure, ii) negative inotropic and chronotropic effects, iii) parasympathetic neuromodulation, iv) vasodilatation, v) anti-inflammatory activity, vi) antioxidant activity, and vii) metabolic effects. OT actions are mediated by nitric oxide and ANP. The beneficial actions of OT may include the increase in glucose uptake by CMs and stem cells, reduction in CM hypertrophy, oxidative stress, and mitochondrial protection of several cell types. In experimentally induced myocardial infarction in rats, continuous in vivo OT delivery improves cardiac healing and cardiac work, reduces inflammation, and stimulates angiogenesis. Because OT plays anti-inflammatory and cardioprotective roles and improves vascular and metabolic functions, it demonstrates potential for therapeutic use in various pathologic conditions

  19. The role of oxytocin in cardiovascular regulation

    Energy Technology Data Exchange (ETDEWEB)

    Gutkowska, J.; Jankowski, M. [University of Montreal, CHUM Research Centre, Faculty of Medicine, Department of Medicine, Laboratory of Cardiovascular Biochemistry, Montreal, Quebec, Canada, Laboratory of Cardiovascular Biochemistry, Department of Medicine, Faculty of Medicine, University of Montreal, CHUM Research Centre, Montreal, Quebec (Canada); Antunes-Rodrigues, J. [Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Fisiologia, Ribeirão Preto, SP, Brasil, Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2014-03-03

    Studies of body volume expansion have indicated that lesions of the anteroventral third ventricle and median eminence block the release of atrial natriuretic peptide (ANP) into the circulation. Detailed analysis of the lesions showed that activation of oxytocin (OT)-ergic neurons is responsible for ANP release, and it has become clear that activation of neuronal circuitry elicits OT secretion into the circulation, activating atrial OT receptors and ANP release from the heart. Subsequently, we have uncovered the entire functional OT system in the rat and the human heart. An abundance of OT has been observed in the early development of the fetal heart, and the capacity of OT to generate cardiomyocytes (CMs) has been demonstrated in various types of stem cells. OT treatment of mesenchymal stem cells stimulates paracrine factors beneficial for cardioprotection. Cardiovascular actions of OT include: i) lowering blood pressure, ii) negative inotropic and chronotropic effects, iii) parasympathetic neuromodulation, iv) vasodilatation, v) anti-inflammatory activity, vi) antioxidant activity, and vii) metabolic effects. OT actions are mediated by nitric oxide and ANP. The beneficial actions of OT may include the increase in glucose uptake by CMs and stem cells, reduction in CM hypertrophy, oxidative stress, and mitochondrial protection of several cell types. In experimentally induced myocardial infarction in rats, continuous in vivo OT delivery improves cardiac healing and cardiac work, reduces inflammation, and stimulates angiogenesis. Because OT plays anti-inflammatory and cardioprotective roles and improves vascular and metabolic functions, it demonstrates potential for therapeutic use in various pathologic conditions.

  20. Concurrent Oxytocin in Women Needing Second Dinoprostone

    International Nuclear Information System (INIS)

    Sher, Z.; Ashraf, M.; Irum, N.; Bashir, S.; Khaliq, N.; Yaqub, S.

    2015-01-01

    Objective: To reduce average induction delivery internal in patients with poor Bishop score without compromising fetomaternal outcome (in terms of birth weight, NICU admission, maternal complications and mode of delivery). Study Design: A descriptive study. Place and Duration of Study: Department of Obstetrics and Gynaecology, Pakistan Atomic Energy Commission (PAEC) General Hospital, Islamabad, from February to December 2009. Methodology: All patients needing 2nd dinoprostone pessary for induction of labour were included in the study. Patients with gestation below 37 weeks, those with intra-uterine growth restriction, bad obstetric history, previous uterine scar and patients in whom Bishop score improved for amniotomy after 1st dinoprostone pessary, were excluded. Data was collected on a special proforma where all variables were defined. Results:Out of 90 patients, 44 (48.8 percentage) had spontaneous vertex deliveries and 12 (13.3 percentage) had instrumental deliveries so a total vaginal deliveries occurred in 56 (62.2 percentage) patients. Thirty four patients (37.8 percentage) had emergency caesarean sections. Main indication for cesarean was failure to progress in 1st stage of labour followed by fetal distress. There were 3 failed inductions. Only 2 patients had hyperstimulation. NICU admission were 8 and all babies were discharged healthy from nursery with no case of early neonatal death. Conclusion:Concurrent oxytocin with 2nd dinoprostone in patients with poor Bishop scores (initial scores 2 and 3) resulted in more vaginal birth and comparatively shorter induction delivery time with almost negligible fetomaternal complications. (author)

  1. Prevention of postpartum haemorrhage with the oxytocin analogue carbetocin.

    Science.gov (United States)

    Rath, Werner

    2009-11-01

    Postpartum haemorrhage is the leading cause of maternal mortality worldwide: 67-80% of cases are caused by uterine atony. Preventive measures include prophylactic drug use to aid uterine contraction after delivery, thus avoiding severe blood loss and reducing maternal morbidity and mortality. Carbetocin is a synthetic analogue of oxytocin with a half-life approximately 4-10 times longer than that reported for oxytocin. It combines the safety and tolerability profile of oxytocin with the sustained uterotonic activity of injectable ergot alkaloids. Furthermore, carbetocin can be administered as a single dose injection either intravenously or intramuscularly rather than as an infusion over several hours as is the case with oxytocin. Carbetocin is currently indicated for prevention of uterine atony after delivery by caesarean section in spinal or epidural anaesthesia. Data from three randomised controlled trials in caesarean delivery and a meta-analysis indicate that carbetocin significantly reduces the need for additional uterotonic agents or uterine massage to prevent excessive bleeding compared with placebo or oxytocin. The risk of headache, tremor, hypotension, flushing, nausea, abdominal pain, pruritus and feeling of warmth was similar in women who received carbetocin or oxytocin. The findings from two more recent double-blind randomised trials and one retrospective study suggest that carbetocin may also represent a good alternative to conventional uterotonic agents for prevention of postpartum haemorrhage after vaginal deliveries. A reduced need for additional uterotonics was observed with carbetocin vs. oxytocin in high-risk women and carbetocin was at least as effective as syntometrine in low-risk women. In these studies of vaginal deliveries, carbetocin was associated with a low incidence of adverse effects and demonstrated a better tolerability profile than syntometrine. Carbetocin had a long duration of action compared with intravenous oxytocin alone and a

  2. Hormonal regulation of phosphatidylcholine synthesis by reversible modulation of cytidylyltransferase.

    Science.gov (United States)

    Kelly, K L; Gutierrez, G; Martin, A

    1988-01-01

    The effect of both lipolytic and antilipolytic hormones on the turnover of phosphatidylcholine in freshly isolated rat adipocytes was investigated. Treatment of adipocytes with agonists such as glucagon or isoprenaline that stimulate lipolysis through a cyclic AMP-dependent mechanism caused an increase in the incorporation of [Me-3H]choline into phosphatidylcholine. Pulse-chase studies indicated that the stimulation was due to an increase in the conversion of choline into phosphatidylcholine, which was both time- and dose-dependent. The stimulatory effect of isoprenaline was inhibited in a dose-dependent manner by oxytocin or insulin. Oxytocin inhibited the incorporation of [Me-3H]choline into phosphatidylcholine in both the presence and the absence of isoprenaline, whereas in the absence of isoprenaline insulin increased the incorporation of [Me-3H]choline into phosphatidylcholine. The effects of isoprenaline, oxytocin and insulin on the incorporation of [3H]choline into phosphatidylcholine were paralleled by changes in the activity of CTP:phosphocholine cytidylyltransferase. PMID:2849424

  3. From autism to eating disorders and more: the role of oxytocin in neuropsychiatric disorders

    Directory of Open Access Journals (Sweden)

    Adele eRomano

    2016-01-01

    Full Text Available Oxytocin (oxy is a nonapeptide hormone synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. Like other neuropeptides, oxy action can simultaneously include regionally and temporally varying combinations of neurotransmitter and neuromodulator activities. Additionally, through the neurohypophysis, oxy is secreted into the systemic circulation to act as a hormone, thereby influencing several body functions. Oxy plays a pivotal role in parturition, milk let-down and maternal behavior and has been demonstrated to be important in the formation of pair bonding between mother and infants as well as in mating pairs. Furthermore oxy is increasingly recognized as an important regulator of social behaviors, including social decision-making, evaluation and response to social stimuli, social interactions and social memory processes. Increasing evidences suggest a crucial role played by oxy in the pathophysiology of certain neuropsychiatric disorders such as autism, eating disorders, schizophrenia, mood and anxiety disorders. The potential use of oxy in these mental health disorders is becoming more and more accepted since many positive effects have been attributed to this neuropeptide.This review will provide an overview of the current understanding on the role played by oxy in different physiological functions and complex behaviors, as well as on its role and impact in different psychiatric disorders, to highlight the need of further investigations on this target that might contribute to the development of novel more efficacious therapies.

  4. A Cortical Circuit for Sexually Dimorphic Oxytocin-Dependent Anxiety Behaviors.

    Science.gov (United States)

    Li, Kun; Nakajima, Miho; Ibañez-Tallon, Ines; Heintz, Nathaniel

    2016-09-22

    The frequency of human social and emotional disorders varies significantly between males and females. We have recently reported that oxytocin receptor interneurons (OxtrINs) modulate female sociosexual behavior. Here, we show that, in male mice, OxtrINs regulate anxiety-related behaviors. We demonstrate that corticotropin-releasing-hormone-binding protein (CRHBP), an antagonist of the stress hormone CRH, is specifically expressed in OxtrINs. Production of CRHBP blocks the CRH-induced potentiation of postsynaptic layer 2/3 pyramidal cell activity of male, but not female, mice, thus producing an anxiolytic effect. Our data identify OxtrINs as critical for modulation of social and emotional behaviors in both females and males and reveal a molecular mechanism that acts on local medial prefrontal cortex (mPFC) circuits to coordinate responses to OXT and CRH. They suggest that additional studies of the impact of the OXT/OXTR and CRHBP/CRH pathways in males and females will be important in development of gender-specific therapies. Published by Elsevier Inc.

  5. Oxytocin--its role in male reproduction and new potential therapeutic uses.

    Science.gov (United States)

    Thackare, Hemlata; Nicholson, Helen D; Whittington, Kate

    2006-01-01

    Oxytocin (OT) is traditionally thought of as a "female" neurohypophysis hormone due to its role in parturition and milk ejection. However, OT is recognized as having endocrine and paracrine roles in male reproduction. At ejaculation, a burst of OT is released from the neurohypophysis into the systemic circulation and stimulates contractions of the reproductive tract aiding sperm release. There is conclusive evidence that OT is synthesized within the mammalian testis, epididymis and prostate and the presence of OT receptors (OTRs) through the reproductive tract supports a local action for this peptide. OT has a paracrine role in stimulating contractility of the seminiferous tubules, epididymis and the prostate gland. Interestingly, OT has also been shown to modulate androgen levels in these tissues via stimulation of the conversion of testosterone to dihydrotestostone (DHT) by 5alpha-reductase. The elucidation of OT's role in male reproduction has suggested a number of potential therapeutic uses for this hormone. Exogenous administration of OT has, in some cases, been shown to increase the numbers of ejaculated sperm, possibly by stimulating contractions of the reproductive tract and thus aiding sperm passage. Within the prostate, OT has been shown to affect gland growth both directly and via its interaction with androgen metabolism. Prostate pathologies due to unregulated cell proliferation/growth, such as benign prostatic hyperplasia and cancer, are unfortunately very common and few effective treatments are available. Greater understanding of paracrine growth mediators, such as OT, is likely to provide new mechanisms for treating such pathologies.

  6. Relationships among estrogen receptor, oxytocin and vasopressin gene expression and social interaction in male mice.

    Science.gov (United States)

    Murakami, G; Hunter, R G; Fontaine, C; Ribeiro, A; Pfaff, D

    2011-08-01

    The incidence of social disorders such as autism and schizophrenia is significantly higher in males, and the presentation more severe, than in females. This suggests the possible contribution of sex hormones to the development of these psychiatric disorders. There is also evidence that these disorders are highly heritable. To contribute toward our understanding of the mechanisms underlying social behaviors, particularly social interaction, we assessed the relationship of social interaction with gene expression for two neuropeptides, oxytocin (OT) and arginine vasopressin (AVP), using adult male mice. Social interaction was positively correlated with: oxytocin receptor (OTR) and vasopressin receptor (V1aR) mRNA expression in the medial amygdala; and OT and AVP mRNA expression in the paraventricular nucleus of the hypothalamus (PVN). When mice representing extremes of social interaction were compared, all of these mRNAs were more highly expressed in high social interaction mice than in low social interaction mice. OTR and V1aR mRNAs were highly correlated with estrogen receptor α (ERα) mRNA in the medial amygdala, and OT and AVP mRNAs with estrogen receptor β (ERβ) mRNA in the PVN, indicating that OT and AVP systems are tightly regulated by estrogen receptors. A significant difference in the level of ERα mRNA in the medial amygdala between high and low social interaction mice was also observed. These results support the hypothesis that variations of estrogen receptor levels are associated with differences in social interaction through the OT and AVP systems, by upregulating gene expression for those peptides and their receptors. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  7. The oxytocin receptor (OXTR contributes to prosocial fund allocations in the dictator game and the social value orientations task.

    Directory of Open Access Journals (Sweden)

    Salomon Israel

    Full Text Available BACKGROUND: Economic games observe social decision making in the laboratory that involves real money payoffs. Previously we have shown that allocation of funds in the Dictator Game (DG, a paradigm that illustrates costly altruistic behavior, is partially determined by promoter-region repeat region variants in the arginine vasopressin 1a receptor gene (AVPR1a. In the current investigation, the gene encoding the related oxytocin receptor (OXTR was tested for association with the DG and a related paradigm, the Social Values Orientation (SVO task. METHODOLOGY/PRINCIPAL FINDINGS: Association (101 male and 102 female students using a robust-family based test between 15 single tagging SNPs (htSNPs across the OXTR was demonstrated with both the DG and SVO. Three htSNPs across the gene region showed significant association with both of the two games. The most significant association was observed with rs1042778 (p = 0.001. Haplotype analysis also showed significant associations for both DG and SVO. Following permutation test adjustment, significance was observed for 2-5 locus haplotypes (p<0.05. A second sample of 98 female subjects was subsequently and independently recruited to play the dictator game and was genotyped for the three significant SNPs found in the first sample. The rs1042778 SNP was shown to be significant for the second sample as well (p = 0.004, Fisher's exact test. CONCLUSIONS: The demonstration that genetic polymorphisms for the OXTR are associated with human prosocial decision making converges with a large body of animal research showing that oxytocin is an important social hormone across vertebrates including Homo sapiens. Individual differences in prosocial behavior have been shown by twin studies to have a substantial genetic basis and the current investigation demonstrates that common variants in the oxytocin receptor gene, an important element of mammalian social circuitry, underlie such individual differences.

  8. Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism.

    Science.gov (United States)

    Patrick, Rhonda P; Ames, Bruce N

    2014-06-01

    Serotonin and vitamin D have been proposed to play a role in autism; however, no causal mechanism has been established. Here, we present evidence that vitamin D hormone (calcitriol) activates the transcription of the serotonin-synthesizing gene tryptophan hydroxylase 2 (TPH2) in the brain at a vitamin D response element (VDRE) and represses the transcription of TPH1 in tissues outside the blood-brain barrier at a distinct VDRE. The proposed mechanism explains 4 major characteristics associated with autism: the low concentrations of serotonin in the brain and its elevated concentrations in tissues outside the blood-brain barrier; the low concentrations of the vitamin D hormone precursor 25-hydroxyvitamin D [25(OH)D3]; the high male prevalence of autism; and the presence of maternal antibodies against fetal brain tissue. Two peptide hormones, oxytocin and vasopressin, are also associated with autism and genes encoding the oxytocin-neurophysin I preproprotein, the oxytocin receptor, and the arginine vasopressin receptor contain VDREs for activation. Supplementation with vitamin D and tryptophan is a practical and affordable solution to help prevent autism and possibly ameliorate some symptoms of the disorder. © FASEB.

  9. Hormonal and molecular effects of restraint stress on formalin-induced pain-like behavior in male and female mice.

    Science.gov (United States)

    Long, Caela C; Sadler, Katelyn E; Kolber, Benedict J

    2016-10-15

    The evolutionary advantages to the suppression of pain during a stressful event (stress-induced analgesia (SIA)) are obvious, yet the reasoning behind sex-differences in the expression of this pain reduction are not. The different ways in which males and females integrate physiological stress responses and descending pain inhibition are unclear. A potential supraspinal modulator of stress-induced analgesia is the central nucleus of the amygdala (CeA). This limbic brain region is involved in both the processing of stress and pain; the CeA is anatomically and molecularly linked to regions of the hypothalamic pituitary adrenal (HPA) axis and descending pain network. The CeA exhibits sex-based differences in response to stress and pain that may differentially induce SIA in males and females. Here, sex-based differences in behavioral and molecular indices of SIA were examined following noxious stimulation. Acute restraint stress in male and female mice was performed prior to intraplantar injections of formalin, a noxious inflammatory agent. Spontaneous pain-like behaviors were measured for 60min following formalin injection and mechanical hypersensitivity was evaluated 120 and 180min post-injection. Restraint stress altered formalin-induced spontaneous behaviors in male and female mice and formalin-induced mechanical hypersensitivity in male mice. To assess molecular indices of SIA, tissue samples from the CeA and blood samples were collected at the 180min time point. Restraint stress prevented formalin-induced increases in extracellular signal regulated kinase 2 (ERK2) phosphorylation in the male CeA, but no changes associated with pERK2 were seen with formalin or restraint in females. Sex differences were also seen in plasma corticosterone concentrations 180min post injection. These results demonstrate sex-based differences in behavioral, molecular, and hormonal indices of acute stress in mice that extend for 180min after stress and noxious stimulation. Copyright

  10. Oxytocin is not involved in luteolysis and early maternal recognition of pregnancy (MRP) in alpacas.

    Science.gov (United States)

    Ciccarelli, Michela; Waqas, Muhammad Salman; Pru, James K; Tibary, Ahmed

    2017-12-01

    Pregnancy maintenance depends on the maternal recognition of pregnancy (MRP), a physiological process by which the lifespan of the corpus luteum is prolonged. This mechanism is not well characterized in camelids. The objectives of the present research were to determine if exogenous oxytocin prolongs the corpus luteum activity in alpacas and to evaluate expression and localization of oxytocin receptors within the endometrium at 9 and 14days post-mating. In the oxytocin studies, plasma progesterone profiles were determined after ovulation in the same alpacas on 2 cycles: one cycle without oxytocin treatment and one cycle with oxytocin treatment. Oxytocin was administered daily by intramuscular injections (IM) at a dose of 20IU (experiment 1, n=6) or 60IU (experiment 2, n=7 from day 3 through day 10 after induction of ovulation with GnRH IM. There was no significant difference in the length of the luteal phase (i.e. corpus luteum lifespan) between the treated and control cycles using either 20 or 60IU of oxytocin. In the final experiment, uteri from open and pregnant alpacas (n=4 per group) at 9 and 14days post-mating were evaluated for expressions of oxytocin receptors by immunohistochemistry. No significant difference (P≤0.05) in the expression of oxytocin receptors was observed between open and pregnant animals in either staining intensity or tissue localization. We conclude that oxytocin is not involved in luteolysis and early MRP in alpacas. Published by Elsevier B.V.

  11. Oxytocin and eating disorders: a narrative review on emerging findings and perspectives.

    Science.gov (United States)

    Giel, Katrin; Zipfel, Stephan; Hallschmid, Manfred

    2017-11-28

    The hypothalamic neuropeptide oxytocin regulates reproductive behavior and mother-infant interaction, and conclusive studies in humans indicate that oxytocin is also a potent modulator of psychosocial function. Pilot experiments have yielded first evidence that this neuropeptide moreover influences eating behavior. Brain administration of oxytocin in animals with normal weight, but also with diet-induced or genetically induced obesity, attenuates food intake and reduces body weight. In normal-weight and obese individuals, acute intranasal oxytocin delivery curbs calorie intake from main dishes and snacks. Such effects might converge with the poignant social and cognitive impact of oxytocin to also improve dysfunctional eating behavior in the therapeutic context. This assumption has received support in first studies showing that oxytocin might play a role in the disease process of anorexia nervosa. In contrast, respective experiments in patients with bulimia nervosa and binge eating disorder are still scarce. We briefly summarize currently available studies on the involvement of the oxytocin system in the pathophysiology of eating disorders, as well as on the effects of oxytocin administration in patients with these disorders. We propose a framework of oxytocin's role and its therapeutic potential in eating disorders that aims at integrating social and metabolic aspects of its pharmacological profile, and ponder perspectives and limitations of oxytocin use in the clinical setting. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Oxytocin modulates GABAAR subunits to confer neuroprotection in stroke in vitro.

    Science.gov (United States)

    Kaneko, Yuji; Pappas, Colleen; Tajiri, Naoki; Borlongan, Cesar V

    2016-10-21

    Oxytocin protects against ischemia-induced inflammation and oxidative stress, and is associated with GABA (γ-aminobutyric acid, an inhibitory neurotransmitter) signaling transduction in neurons. However, the molecular mechanism by which oxytocin affords neuroprotection, especially the interaction between oxytocin receptor and GABA A receptor (GABA A R), remains to be elucidated. Primary rat neural cells were exposed to oxytocin before induction of experimental acute stroke model via oxygen-glucose deprivation-reperfusion (OGD/R) injury. Pretreatment with oxytocin increased cell viability, decreased the cell damage against oxidative stress, and prevented the release of high mobility group box1 during OGD/R. However, introduction of oxytocin during OGD/R did not induce neuroprotection. Although oxytocin did not affect the glutathione-related cellular metabolism before OGD, oxytocin modulated the expression levels of GABA A R subunits, which function to remove excessive neuronal excitability via chloride ion influx. Oxytocin-pretreated cells significantly increased the chloride ion influx in response to GABA and THIP (δ-GABA A R specific agonist). This study provides evidence that oxytocin regulated GABA A R subunits in affording neuroprotection against OGD/R injury.

  13. Bioidentical Hormones and Menopause

    Science.gov (United States)

    ... Endocrinologist Search Featured Resource Menopause Map™ View Bioidentical Hormones January 2012 Download PDFs English Espanol Editors Howard ... take HT for symptom relief. What are bioidentical hormones? Bioidentical hormones are identical to the hormones that ...

  14. The Role of Oxytocin in Parenting and as Augmentative Pharmacotherapy: Critical Issues and Bold Conjectures.

    Science.gov (United States)

    van IJzendoorn, M H; Bakermans-Kranenburg, M J

    2016-08-01

    Despite the sometimes heated debate about the validity of human oxytocin studies, experimental oxytocin research with intranasal administration is a growing field with promising preliminary findings. The effects of intranasally administered oxytocin compared to placebo on brain neural activity have been supported in animal studies and in human studies of neural resting state. In several studies, oxytocin sniffs have been shown to lead to down-regulation of amygdala activation in response to infant attachment vocalisations. Meta-analytic evidence shows that oxytocin enhances the salience of (emotional) stimuli, lowers stress and arousal, and elevates empathic concern and tender care, in particular for offspring and in-group members. Less firm evidence points at the amnestic effects of oxytocin. We also note that the average effect sizes of oxytocin experiments are small to modest, and that most studies include a small number of subjects and thus are seriously underpowered, which implies a high risk for publication bias and nonreplicability. Nevertheless, we argue that the power of within-subjects experiments with oxytocin has been underestimated. Much more work is needed, however, to create a firm knowledge base of the neural and behavioural effects of oxytocin. Human oxytocin research is still taking place in the context of discovery, in which bold conjectures are being generated. In the context of justification, these conjectures should subsequently be subjected to stringent attempts at refutations before we jump to theoretical or clinical conclusions. For this context of justification, we propose a multisite multiple replications project on the social stimuli salience enhancing effect of oxytocin. Clinical application of oxytocin is premature. Meta-analytically, the use of oxytocin in clinical groups tends to show only effectiveness in changing symptomatology in individuals with autism spectrum disorders but, even then, it is not yet a validated therapy and its

  15. The stress system in the human brain in depression and neurodegeneration.

    Science.gov (United States)

    Swaab, Dick F; Bao, Ai-Min; Lucassen, Paul J

    2005-05-01

    Corticotropin-releasing hormone (CRH) plays a central role in the regulation of the hypothalamic-pituitary-adrenal (HPA)-axis, i.e., the final common pathway in the stress response. The action of CRH on ACTH release is strongly potentiated by vasopressin, that is co-produced in increasing amounts when the hypothalamic paraventricular neurons are chronically activated. Whereas vasopressin stimulates ACTH release in humans, oxytocin inhibits it. ACTH release results in the release of corticosteroids from the adrenal that, subsequently, through mineralocorticoid and glucocorticoid receptors, exert negative feedback on, among other things, the hippocampus, the pituitary and the hypothalamus. The most important glucocorticoid in humans is cortisol, present in higher levels in women than in men. During aging, the activation of the CRH neurons is modest compared to the extra activation observed in Alzheimer's disease (AD) and the even stronger increase in major depression. The HPA-axis is hyperactive in depression, due to genetic factors or due to aversive stimuli that may occur during early development or adult life. At least five interacting hypothalamic peptidergic systems are involved in the symptoms of major depression. Increased production of vasopressin in depression does not only occur in neurons that colocalize CRH, but also in neurons of the supraoptic nucleus (SON), which may lead to increased plasma levels of vasopressin, that have been related to an enhanced suicide risk. The increased activity of oxytocin neurons in the paraventricular nucleus (PVN) may be related to the eating disorders in depression. The suprachiasmatic nucleus (SCN), i.e., the biological clock of the brain, shows lower vasopressin production and a smaller circadian amplitude in depression, which may explain the sleeping problems in this disorder and may contribute to the strong CRH activation. The hypothalamo-pituitary thyroid (HPT)-axis is inhibited in depression. These hypothalamic

  16. Paradoxical effects of oxytocin and vasopressin on basal prolactin secretion and the estrogen-induced prolactin surge

    International Nuclear Information System (INIS)

    Mai, Leemin; Pan, Jenntser

    1990-01-01

    The roles of oxytocin (OT) and vasopressin (AVP) on both basal and estrogen-induced prolactin (PRL) secretion were examined. Adult female Sprague-Dawley rats that were ovariectomized for 3 weeks and received estrogen treatment for 1 week were used. Intravenous administration of hormones and serial blood sampling were accomplished through indwelling intraatrial catheters which were implanted two days before. Plasma PRL levels were measured by radioimmunoassay. Oxytocin at a dose of 20 μg/rat stimulated a moderate PRL release in the morning and lower doses were without effect. Vasopressin was most effective at a dose of 5 μg/rat in stimulating PRL release, while consecutive injections of higher doses were less effective. In contrast, TRH, ranging from 1 to 8 μg/rat, induced a dose-dependent increases in PRL secretion. Using the effective dosages determined from the morning studies, repeated injections of either OT, AVP or their specific antagonists MPOMeOVT were given hourly between 1300 to 1800h and blood samples were obtained hourly from 1100 to 1900h. It was found that either OT or AVP significantly reduced the afternoon PRL surge, while their antagonists were not as effective

  17. A paradoxical association of an oxytocin receptor gene polymorphism: Early-life adversity and vulnerability to depression

    Directory of Open Access Journals (Sweden)

    Robyn Jane McQuaid

    2013-07-01

    Full Text Available Several prosocial behaviors may be influenced by the hormone oxytocin. In line with this perspective, the oxytocin receptor (OXTR gene single nucleotide polymorphism (SNP, rs53576, has been associated with a broad range of social behaviors. In this regard, the G allele of the OXTR SNP has been accompanied by beneficial attributes such as increased empathy, optimism and trust. In the current study among university students (N = 288, it was shown that early-life maltreatment was associated with depressive symptoms, and that the OXTR genotype moderated this relationship, such that under high levels of childhood maltreatment, only individuals with GG/GA genotype demonstrated increased depressive symptomatology compared to those with the AA genotype. In addition, the role of distrust in mediating the relation between childhood maltreatment and depression seemed to be more important among G allele carriers compared to individuals with the AA genotype. Thus, a breach in trust (i.e. in the case of early-life abuse or neglect may have a more deleterious effect among G carriers, who have been characterized as more prosocial and attuned to social cues. The data suggested that G carriers of the OXTR might favor social sensitivity and thus might have been more vulnerable to the effects of early-life adversity.

  18. Modulating the Oxytocin System During the Perinatal Period: A New Strategy for Neuroprotection of the Immature Brain?

    Directory of Open Access Journals (Sweden)

    Manuela Zinni

    2018-04-01

    Full Text Available Oxytocin is a neurohypophysal hormone known for its activity during labor and its role in lactation. However, the function of oxytocin (OTX goes far beyond the peripheral regulation of reproduction, and the central effects of OTX have been extensively investigated, since it has been recognized to influence the learning and memory processes. OTX has also prominent effects on social behavior, anxiety, and autism. Interaction between glucocorticoids, OTX, and maternal behavior may have long-term effects on the developmental program of the developing brain subjected to adverse events during pre and perinatal periods. OTX treatment in humans improves many aspects of social cognition and behavior. Its effects on the hypothalamic–pituitary–adrenal axis and inflammation appear to be of interest in neonates because these properties may confer benefits when the perinatal brain has been subjected to injury. Indeed, early life inflammation and abnormal adrenal response to stress have been associated with an abnormal white matter development. Recent investigations demonstrated that OTX is involved in the modulation of microglial reactivity in the developing brain. This review recapitulates state-of-the art data supporting the hypothesis that the OTX system could be considered as an innovative candidate for neuroprotection, especially in the immature brain.

  19. Antiaggressive activity of central oxytocin in male rats

    NARCIS (Netherlands)

    Calcagnoli, F.; de Boer, S.F.; Althaus, M.; den Boer, J.A.; Koolhaas, J.M.

    2013-01-01

    A substantial body of research suggests that the neuropeptide oxytocin promotes social affiliative behaviors in a wide range of animals including humans. However, its antiaggressive action has not been unequivocally demonstrated in male laboratory rodents. Our primary goal was to examine the

  20. The role of oxytocin in male and female reproductive behavior

    NARCIS (Netherlands)

    Veening, J.G.; Jong, T.R. de; Waldinger, M.D.; Korte, S.M.; Olivier, B.

    2015-01-01

    Oxytocin (OT) is a nonapeptide with an impressive variety of physiological functions. Among them, the 'prosocial' effects have been discussed in several recent reviews, but the direct effects on male and female sexual behavior did receive much less attention so far. As our contribution to honor the

  1. Effect of estradiol and oxytocin on ovine cervical relaxation

    African Journals Online (AJOL)

    Yomi

    2012-02-07

    Feb 7, 2012 ... The aim of this study was to examine the effect of estradiol (E2) and oxytocin ... Artificial insemination (AI) is a good way for the use of superior rams in reproduction but the conception rates in ... successful in sheep industry because it is costly, time .... during luteolysis and its abrogation in early pregnancy.

  2. Oxytocin and Serotonin Brain Mechanisms in the Nonhuman Primate.

    Science.gov (United States)

    Lefevre, Arthur; Richard, Nathalie; Jazayeri, Mina; Beuriat, Pierre-Aurélien; Fieux, Sylvain; Zimmer, Luc; Duhamel, Jean-René; Sirigu, Angela

    2017-07-12

    Oxytocin (OT) is increasingly studied for its therapeutic potential in psychiatric disorders, which are associated with the deregulation of several neurotransmission systems. Studies in rodents demonstrated that the interaction between OT and serotonin (5-HT) is critical for several aspects of social behavior. Using PET scan in humans, we have recently found that 5-HT 1A receptor (5-HT 1A R) function is modified after intranasal oxytocin intake. However, the underlying mechanism between OT and 5-HT remains unclear. To understand this interaction, we tested 3 male macaque monkeys using both [ 11 C]DASB and [ 18 F]MPPF, two PET radiotracers, marking the serotonin transporter and the 5-HT 1A R, respectively. Oxytocin (1 IU in 20 μl of ACSF) or placebo was injected into the brain lateral ventricle 45 min before scans. Additionally, we performed postmortem autoradiography. Compared with placebo, OT significantly reduced [ 11 C]DASB binding potential in right amygdala, insula, and hippocampus, whereas [ 18 F]MPPF binding potential increased in right amygdala and insula. Autoradiography revealed that [ 11 C]DASB was sensitive to physiological levels of 5-HT modification, and that OT does not act directly on the 5-HT 1A R. Our results show that oxytocin administration in nonhuman primates influences serotoninergic neurotransmission via at least two ways: (1) by provoking a release of serotonin in key limbic regions; and (2) by increasing the availability of 5-HT 1A R receptors in the same limbic areas. Because these two molecules are important for social behavior, our study sheds light on the specific nature of their interaction, therefore helping to develop new mechanisms-based therapies for psychiatric disorders. SIGNIFICANCE STATEMENT Social behavior is largely controlled by brain neuromodulators, such as oxytocin and serotonin. While these are currently targeted in the context of psychiatric disorders such as autism and schizophrenia, a new promising pharmaceutical

  3. Helping Oxytocin Deliver: Considerations in the Development of Oxytocin-Based Therapeutics for Brain Disorders.

    Directory of Open Access Journals (Sweden)

    Kai eMacdonald

    2013-03-01

    Full Text Available Concerns regarding a drought in psychopharmacology have risen from many quarters. From one perspective, the wellspring of bedrock medications for anxiety disorders, depression, and schizophrenia was serendipitously discovered over thirty year ago, the swell of pharmaceutical investment in drug discovery has receded, and the pipeline’s flow of medications with unique mechanisms of action (i.e. glutamatergic agents, CRF antagonists has slowed to a trickle. Might oxytocin (OT-based therapeutics be an oasis? Though a large basic science literature and a slowly increasing number of studies in human diseases support this hope, the bulk of extant OT studies in humans are single-dose studies on normals, and do not directly relate to improvements in human brain-based diseases. Instead, these studies have left us with a field pregnant with therapeutic possibilities, but barren of definitive treatments. In this clinically-oriented review, we discuss the extant OT literature with an eye toward helping OT deliver on its promise as a therapeutic agent. To this end, we identify ten key questions that we believe future OT research should address. From this overview, several conclusions are clear: 1 the OT system represents an extremely promising target for novel CNS drug development; 2 there is a pressing need for rigorous, randomized controlled clinical trials targeting actual patients; and 3 in order to inform the design and execution of these vital trials, we need further translational studies addressing the questions posed in this review. Looking forward, we extend a cautious hope that the next decade of OT research will birth oxytocin-targetted therapeutics that can truly deliver on this system’s therapeutic potential.

  4. Oxytocin and the oxytocin receptor underlie intrastrain, but not interstrain, social recognition.

    Science.gov (United States)

    Macbeth, A H; Lee, H-J; Edds, J; Young, W S

    2009-07-01

    We studied three lines of oxytocin (Oxt) and oxytocin receptor (Oxtr) knockout (KO) male mice [Oxt(-/-), total Oxtr(-/-) and partial forebrain Oxtr (Oxtr(FB/FB))] with established deficits in social recognition to further refine our understanding of their deficits with regard to stimulus female's strain. We used a modified social discrimination paradigm in which subjects are singly housed only for the duration of the test. Additionally, stimulus females are singly housed throughout testing and are presented within corrals for rapid comparison of investigation by subject males. Wild-type (WT) males from all three lines discriminated between familiar and novel females of three different strains (C57BL/6, BALB/c and Swiss-Webster). No KO males discriminated between familiar and novel BALB/c or C57BL/6 females. Male Oxt(-/-) and Oxtr(-/-) mice, but not Oxtr(FB/FB) mice, discriminated between familiar and novel Swiss-Webster females. As this might indicate a global deficit in individual recognition for Oxtr(FB/FB) males, we examined their ability to discriminate between females from different strains and compared performance with Oxtr(-/-) males. WT and KO males from both lines were able to distinguish between familiar and novel females from different strains, indicating the social recognition deficit is not universal. Instead, we hypothesize that the Oxtr is involved in 'fine' intrastrain recognition, but is less important in 'broad' interstrain recognition. We also present the novel finding of decreased investigation across tests, which is likely an artifact of repeated testing and not because of stimulus female's strain or age of subject males.

  5. De-masking oxytocin-deficiency in craniopharyngioma and assessing its link with affective function.

    Science.gov (United States)

    Gebert, Dorothea; Auer, Matthias K; Stieg, Mareike R; Freitag, Martin T; Lahne, Madlén; Fuss, Johannes; Schilbach, Katharina; Schopohl, Jochen; Stalla, Günter K; Kopczak, Anna

    2018-02-01

    Despite the high prevalence of panhypopituitarism and diabetes insipidus in patients with craniopharyngioma (CP), little is known about the functioning of the neuropeptide oxytocin in these patients. This is of special interest as tumor-associated lesions often impair sites critical for oxytocin production and release, and affective dysfunction in CP links with elsewhere reported prosocial, antidepressant and anxiolytic oxytocin effects. Using a prospective study-design, we tested whether oxytocin is reduced in CP-patients, and whether altered oxytocin levels account for affective and emotional dysfunction. 26 adult CP-patients and 26 healthy controls matched in sex and age underwent physical exercise, a stimulus previously shown to induce oxytocin release. Baseline and stimulated salivary oxytocin levels, as well as empathy, depression and anxiety scores were measured. Results showed that patients overall did not present with lower baseline oxytocin levels than controls (F[1,30]=0.21, p=0.649), but baseline oxytocin levels were indeed reduced in patients with hypothalamic damage, as assessed by MRI-based grading (F[2,9.79]=4.54, p=0.040). In response to exercise-induced stimulation, all CP-patients showed a blunted oxytocin-release compared to controls (F[1,30]=9.36, p=0.005). DI was not associated with oxytocin levels. Regarding affective function, unexpectedly, higher baseline oxytocin was related to higher trait anxiety (b=2.885, t(43)=2.421, p=0.020, CI[.478; 5.292]); the positive link with higher depression failed to reach statistical significance (b=1.928, t(43)=1.949, p=0.058, CI[-0.070; 3.927]). A blunted oxytocin-release was linked with higher state anxiety (b=-0.133, t(43)=-2.797, p=0.008, CI[-0.230; -0.037]). Empathy was not associated with oxytocin measures. In conclusion, we observed reduced baseline oxytocin levels only in CP-patients with hypothalamic damage. Exercise-induced stimulation de-masked an oxytocin-deficiency in all CP-patients. Baseline

  6. Effect of the nature of subsequent environment on oxytocin and cortisol secretion in maltreated children

    Directory of Open Access Journals (Sweden)

    Sakae G. Mizushima

    2015-12-01

    Full Text Available Childhood maltreatment (CM, including abuse and neglect is a crucial factor that distorts child development. CM is associated with alterations in numerous brain regions, and may be associated with neuropeptide hormonal dysregulation. This study aimed to investigate differences in secretion patterns of cortisol (CT and oxytocin (OT among children who experienced CM, children living in residential care facilities and in unstable environments. Among 38 maltreated children, 23 (mean age = 12.2 years, SD = 3.0 were categorized as Settled and 15 (mean age = 13.1 years, SD = 2.2 as Unsettled. Twenty-six age- and gender-matched (mean age = 12.6 years, SD = 2.1, typically developing (TD children were also included. Clinical and psychological assessments, including IQ and trauma evaluations were conducted for all participants. Age, gender and full-scale IQ were used as covariates in hormone analysis. Two saliva samples were collected, one on awakening, the other at bedtime. There were significant differences in the awakening CT levels of the Unsettled group, and in bedtime OT levels in the Settled group as compared with TD children, and between CM groups. Furthermore, there was a significant difference in trauma-symptomatic depression scores between the Settled and Unsettled CM group. These results suggest that CT diurnal secretions tend to be reactive to current stress rather previous experience. OT diurnal secretions are presumably hyper-regulated for coping with the environment to survive and thrive. By measuring salivary CT/OT diurnal patterns, hormonal dysregulation of CM children living in Settled environments and Unsettled environments was indicated.

  7. The Association Between Progesterone, Estradiol, and Oxytocin and Heat Pain Measures in Pregnancy: An Observational Cohort Study.

    Science.gov (United States)

    Frölich, Michael A; Banks, Catiffaney; Warren, William; Robbins, Meredith; Ness, Timothy

    2016-08-01

    Hormonal action has been implicated as a possible mechanism for pregnancy-induced analgesia. Previous investigators have reported an increase in heat pain tolerance during labor compared with nonpregnant controls and postulated it was because of the hormonal changes during pregnancy. However, these previous reports did not include measurement of hormonal values. The purpose of our study was to quantitatively test if changes in pregnancy hormone concentrations correlated with changes in temperature ratings. This was a prospective cohort study consisting of 32 women scheduled for elective cesarean delivery at term between July 2010 and January 2013. Heat pain threshold and tolerance, estrogen, progesterone, and oxytocin levels were measured twice in each patient at term and again 4 to 8 weeks postpartum. All hormone levels decreased significantly between term pregnancy and the postpartum visit (all P values heat pain measurements. The mean baseline heat pain threshold was 40.9°C at term compared with 40.3°C °postpartum (P = 0.47; mean change, -0.6°C; 95% confidence interval of change, -1.8°C to +0.7°C). The mean baseline heat pain tolerance was 46.1°C at term and 46.0°C postpartum (P = 0.59; mean change, -0.1°C; 95% confidence interval of change, -0.8°C° to +0.6°C). Our findings show that amounts of estradiol and progesterone changed significantly between the term and the postpartum visit; however, the thermal pain tolerance did not significantly change. In summary, we did not observe an association between hormonal changes and changes in pain threshold measures. This finding argues against the concept of simple progesterone- or estrogen-induced analgesia in humans.

  8. Prenatal stress puzzle, the oxytocin piece: Prenatal stress alters the behaviour and autonomic regulation in piglets, insights from oxytocin

    Science.gov (United States)

    Developmental changes in response to prenatal stressors (PNS) may represent an adaptive strategy to enhance survival traits in the offspring. Yet, PNS could be maladaptive for captive animals, causing anxiety and abnormal social development. Oxytocin (OT) reduces anxiety, whereas OT deficiencies are...

  9. Characteristics of temporal patterns of cortisol and luteinizing hormone in primiparous, postpartum, anovular, suckled, beef cows exposed acutely to bulls

    Directory of Open Access Journals (Sweden)

    Tauck Shaun A

    2010-07-01

    Full Text Available Abstract Background The physiological mechanism by which bulls stimulate resumption of ovarian cycling activity in postpartum, anovular, suckled cows after calving may involve the concurrent activation of the hypothalamic-hypophyseal-ovarian (HPO axis and hypothalamic-hypophyseal-adrenal (HPA axis. Thus, the objectives of this experiment were to determine if characteristics of temporal patterns of cortisol and luteinizing hormone (LH in postpartum, anovular, beef cows are influenced by acute exposure to bulls. The null hypotheses were that daily, temporal characteristics of cortisol and LH concentration patterns do not differ between cows exposed acutely to bulls or steers. Methods Sixteen cows were assigned randomly 67 +/- 4 (+/- SE after calving to be exposed to bulls (EB, n = 8 or steers (ES, n = 8 5 h daily for 9 d (D 0 to 8. Blood samples were collected daily from each cow via jugular catheters at 15-min intervals for 6 h from 1000 to 1600 h each day. The 5-h exposure period began 1 h after the start of the intensive bleeding period. Characteristics of cortisol and LH concentration patterns (mean, baseline, pulse frequency, pulse amplitude, and pulse duration were identified by PULSAR analyses. Results Mean cortisol concentrations decreased (P 0.10 between EB and ES cows. The decrease in mean cortisol concentrations in EB and ES cows from D 0 to D 2 was attributed to cows acclimatizing to intensive blood sampling and handling procedures. Consequently, analyses for characteristics of cortisol and LH concentration patterns included D 2 through 8 only. Cortisol mean and baseline concentrations, and pulse amplitude did not differ (P > 0.10 between EB and ES cows. However, cortisol pulse duration tended to be longer (P = 0.09 and pulse frequency was lower (P = 0.05 in EB than ES cows. LH pulse frequency was greater (P = 0.06 in EB than ES cows. All other characteristics of LH concentration patterns did not differ (P > 0.10 between EB and ES cows

  10. Oxytocin Attenuates Neural Reactivity to Masked Threat Cues from the Eyes

    OpenAIRE

    Kanat, Manuela; Heinrichs, Markus; Schwarzwald, Ralf; Domes, Gregor

    2014-01-01

    The neuropeptide oxytocin has recently been shown to modulate covert attention shifts to emotional face cues and to improve discrimination of masked facial emotions. These results suggest that oxytocin modulates facial emotion processing at early perceptual stages prior to full evaluation of the emotional expression. Here, we used functional magnetic resonance imaging to examine whether oxytocin alters neural responses to backwardly masked angry and happy faces while controlling for attention...

  11. Oxytocin in pregnancy and the postpartum: relations to labor and its management

    Directory of Open Access Journals (Sweden)

    Marie ePrevost

    2014-01-01

    Full Text Available The purpose of this study was to examine variations in endogenous oxytocin levels in pregnancy and postpartum state. We also explored the associations between delivery variables and oxytocin levels. A final sample of 272 mothers in their first trimester of pregnancy were included for the study. Blood samples were drawn during the 1st trimester and 3rd trimester of pregnancy and at 8 weeks postpartum. Socio-demographic data were collected at each time point and medical files were consulted for delivery details. In most women, levels of circulating oxytocin increased from the 1st to 3rd trimester of pregnancy followed by a decrease in the postpartum period. Oxytocin levels varied considerably between individuals, ranging from 50 pg/mL to over 2000 pg/mL. Parity was the main predictor of oxytocin levels in the 3rd trimester of pregnancy and of oxytocin level changes from the 1st to the 3rd trimester of pregnancy. Oxytocin levels in the 3rd trimester of pregnancy predicted a self-reported negative labor experience and increased the chances of having an epidural. Intrapartum exogenous oxytocin was positively associated with levels of oxytocin during the postpartum period. Our exploratory results suggest that circulating oxytocin levels during the 3rd trimester of pregnancy may predict the type of labor a woman will experience. More importantly, the quantity of intrapartum exogenous oxytocin administered during labor predicted plasma oxytocin levels 2 months postpartum, suggesting a possible long-term effect of this routine intervention, the consequences of which are largely unknown.

  12. Oxytocin increases bias, but not accuracy, in face recognition line-ups

    OpenAIRE

    Bate, Sarah; Bennetts, Rachel; Parris, Benjamin A.; Bindemann, Markus; Udale, Robert; Bussunt, Amanda

    2014-01-01

    Previous work indicates that intranasal inhalation of oxytocin improves face recognition skills, raising the possibility that it may be used in security settings. However, it is unclear whether oxytocin directly acts upon the core face-processing system itself, or indirectly improves face recognition via affective or social salience mechanisms. In a double-blind procedure, 60 participants received either an oxytocin or placebo nasal spray before completing the One-in-Ten task – a standardized...

  13. Restoring effects of oxytocin on the attentional preference for faces in autism

    OpenAIRE

    Kanat, M; Spenthof, I; Riedel, A; van Elst, L T; Heinrichs, M; Domes, G

    2017-01-01

    Reduced attentional preference for faces and symptoms of social anxiety are common in autism spectrum disorders (ASDs). The neuropeptide oxytocin triggers anxiolytic functions and enhances eye gaze, facial emotion recognition and neural correlates of face processing in ASD. Here we investigated whether a single dose of oxytocin increases attention to faces in ASD. As a secondary question, we explored the influence of social anxiety on these effects. We tested for oxytocin's effects on attenti...

  14. Oxytocin signaling in mouse taste buds.

    Directory of Open Access Journals (Sweden)

    Michael S Sinclair

    2010-08-01

    Full Text Available The neuropeptide, oxytocin (OXT, acts on brain circuits to inhibit food intake. Mutant mice lacking OXT (OXT knockout overconsume salty and sweet (i.e. sucrose, saccharin solutions. We asked if OXT might also act on taste buds via its receptor, OXTR.Using RT-PCR, we detected the expression of OXTR in taste buds throughout the oral cavity, but not in adjacent non-taste lingual epithelium. By immunostaining tissues from OXTR-YFP knock-in mice, we found that OXTR is expressed in a subset of Glial-like (Type I taste cells, and also in cells on the periphery of taste buds. Single-cell RT-PCR confirmed this cell-type assignment. Using Ca2+ imaging, we observed that physiologically appropriate concentrations of OXT evoked [Ca2+]i mobilization in a subset of taste cells (EC50 approximately 33 nM. OXT-evoked responses were significantly inhibited by the OXTR antagonist, L-371,257. Isolated OXT-responsive taste cells were neither Receptor (Type II nor Presynaptic (Type III cells, consistent with our immunofluorescence observations. We also investigated the source of OXT peptide that may act on taste cells. Both RT-PCR and immunostaining suggest that the OXT peptide is not produced in taste buds or in their associated nerves. Finally, we also examined the morphology of taste buds from mice that lack OXTR. Taste buds and their constituent cell types appeared very similar in mice with two, one or no copies of the OXTR gene.We conclude that OXT elicits Ca2+ signals via OXTR in murine taste buds. OXT-responsive cells are most likely a subset of Glial-like (Type I taste cells. OXT itself is not produced locally in taste tissue and is likely delivered through the circulation. Loss of OXTR does not grossly alter the morphology of any of the cell types contained in taste buds. Instead, we speculate that OXT-responsive Glial-like (Type I taste bud cells modulate taste signaling and afferent sensory output. Such modulation would complement central pathways of

  15. Oxytocin signaling in mouse taste buds.

    Science.gov (United States)

    Sinclair, Michael S; Perea-Martinez, Isabel; Dvoryanchikov, Gennady; Yoshida, Masahide; Nishimori, Katsuhiko; Roper, Stephen D; Chaudhari, Nirupa

    2010-08-05

    The neuropeptide, oxytocin (OXT), acts on brain circuits to inhibit food intake. Mutant mice lacking OXT (OXT knockout) overconsume salty and sweet (i.e. sucrose, saccharin) solutions. We asked if OXT might also act on taste buds via its receptor, OXTR. Using RT-PCR, we detected the expression of OXTR in taste buds throughout the oral cavity, but not in adjacent non-taste lingual epithelium. By immunostaining tissues from OXTR-YFP knock-in mice, we found that OXTR is expressed in a subset of Glial-like (Type I) taste cells, and also in cells on the periphery of taste buds. Single-cell RT-PCR confirmed this cell-type assignment. Using Ca2+ imaging, we observed that physiologically appropriate concentrations of OXT evoked [Ca2+]i mobilization in a subset of taste cells (EC50 approximately 33 nM). OXT-evoked responses were significantly inhibited by the OXTR antagonist, L-371,257. Isolated OXT-responsive taste cells were neither Receptor (Type II) nor Presynaptic (Type III) cells, consistent with our immunofluorescence observations. We also investigated the source of OXT peptide that may act on taste cells. Both RT-PCR and immunostaining suggest that the OXT peptide is not produced in taste buds or in their associated nerves. Finally, we also examined the morphology of taste buds from mice that lack OXTR. Taste buds and their constituent cell types appeared very similar in mice with two, one or no copies of the OXTR gene. We conclude that OXT elicits Ca2+ signals via OXTR in murine taste buds. OXT-responsive cells are most likely a subset of Glial-like (Type I) taste cells. OXT itself is not produced locally in taste tissue and is likely delivered through the circulation. Loss of OXTR does not grossly alter the morphology of any of the cell types contained in taste buds. Instead, we speculate that OXT-responsive Glial-like (Type I) taste bud cells modulate taste signaling and afferent sensory output. Such modulation would complement central pathways of appetite

  16. Oxytocin attenuates aversive response to nicotine and anxiety-like behavior in adolescent rats.

    Science.gov (United States)

    Lee, Hyunchan; Jang, Minji; Noh, Jihyun

    2017-02-01

    Initial tobacco use is initiated with rewarding and aversive properties of nicotine and aversive response to nicotine plays a critical role in nicotine dependency. Decrease of nicotine aversion increases the nicotine use that causes behavioral and neuronal changes of animals. Oxytocin influences drug abuse and reciprocally affect vulnerability to drug use. To assess the effect of oxytocin on initial nicotine aversion and anxiety, we examined voluntary oral nicotine intake and anxiety-like behavior following oxytocin treatment in adolescent rats. Sprague-Dawley male rats (4 weeks old) were used. For oxytocin administration, rats were injected subcutaneously with saline or oxytocin (0.01, 0.1 and 1mg/kg) according to the assigned groups. Voluntary oral nicotine consumption test was performed by two bottle free-choice paradigm. To examine anxiety-like behavior in rats, we performed a light/dark box test. Oxytocin not only significantly increased the nicotine intake but also alleviated nicotine aversion after acclimation to nicotine solution in a concentration dependent manner. Meanwhile, oxytocin significantly reduced anxiety-like behavior. We suggest that oxytocin itself mitigates aversive response toward initial nicotine intake and anxiety-like behavior. These results widen the psychophysiological perspective on oxytocin for better understanding of nicotine addiction related behaviors influenced by diverse social factors. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  17. Plasma Oxytocin Immunoreactive Products and Response to Trust in Patients with Social Anxiety Disorder

    Science.gov (United States)

    Hoge, EA; Lawson, EA; Metcalf, CA; Keshaviah, A; Zak, PJ; Pollack, MH; Simon, NM

    2013-01-01

    Background Generalized Social Anxiety Disorder (GSAD) is characterized by excessive fear and avoidance of several types of social and performance situations. The pathophysiology is not well understood, but research in animals and humans has provided evidence that oxytocin helps regulate normal social affiliative behavior. Previous work in healthy male subjects demonstrated a rise in plasma oxytocin after receiving a high trust signal. To examine the oxytocin system in GSAD, we measured plasma oxytocin in GSAD patients and controls, before and after the social “Trust Game,” a neuroeconomic test examining trust behavior and reaction to trust using real monetary incentives. Methods Thirty-nine subjects with GSAD and 28 healthy controls provided three blood samples for oxytocin measurement before the Trust Game, and one sample after the game. Plasma estradiol was also measured at baseline. The Trust Game protocol version prioritized the sending of a signal of high cooperation and trust to all participants. All analyses controlled for gender and estradiol levels. Results Mean oxytocin levels post-Trust Game (p=0.025), and overall (area under the curve, p=0.011) were lower in GSAD patients compared to controls, after controlling for sex and estradiol. There was no significant change in oxytocin levels after the Game in either group. Conclusions We report low plasma oxytocin levels in patients with generalized social anxiety disorder during a pro-social laboratory task paradigm. Additional research will be important to further examine the relationship between oxytocin and social behavior in GSAD. PMID:22807189

  18. The Neuropeptide Oxytocin Enhances Information Sharing and Group Decision Making Quality.

    Science.gov (United States)

    De Wilde, Tim R W; Ten Velden, Femke S; De Dreu, Carsten K W

    2017-01-11

    Groups can make better decisions than individuals when members cooperatively exchange and integrate their uniquely held information and insights. However, under conformity pressures group members are biased towards exchanging commonly known information, and away from exchanging unique information, thus undermining group decision-making quality. At the neurobiological level, conformity associates with the neuropeptide oxytocin. A double-blind placebo controlled study found no evidence for oxytocin induced conformity. Compared to placebo groups, three-person groups whose members received intranasal oxytocin, focused more on unique information (i) and repeated this information more often (ii). These findings reveal oxytocin as a neurobiological driver of group decision-making processes.

  19. Role of nucleus of the solitary tract noradrenergic neurons in post-stress cardiovascular and hormonal control in male rats.

    Science.gov (United States)

    Bundzikova-Osacka, Jana; Ghosal, Sriparna; Packard, Benjamin A; Ulrich-Lai, Yvonne M; Herman, James P

    2015-01-01

    Chronic stress causes hypothalamo-pituitary-adrenal (HPA) axis hyperactivity and cardiovascular dyshomeostasis. Noradrenergic (NA) neurons in the nucleus of the solitary tract (NTS) are considered to play a role in these changes. In this study, we tested the hypothesis that NTS NA A2 neurons are required for cardiovascular and HPA axis responses to both acute and chronic stress. Adult male rats received bilateral microinjection into the NTS of 6-hydroxydopamine (6-OHDA) to lesion A2 neurons [cardiovascular study, n = 5; HPA study, n = 5] or vehicle [cardiovascular study, n = 6; HPA study, n = 4]. Rats were exposed to acute restraint stress followed by 14 d of chronic variable stress (CVS). On the last day of testing, rats were placed in a novel elevated plus maze (EPM) to test post-CVS stress responses. Lesions of NTS A2 neurons reduced the tachycardic response to acute restraint, confirming that A2 neurons promote sympathetic activation following acute stress. In addition, CVS increased the ratio of low-frequency to high-frequency power for heart rate variability, indicative of sympathovagal imbalance, and this effect was significantly attenuated by 6-OHDA lesion. Lesions of NTS A2 neurons reduced acute restraint-induced corticosterone secretion, but did not affect the corticosterone response to the EPM, indicating that A2 neurons promote acute HPA axis responses, but are not involved in CVS-mediated HPA axis sensitization. Collectively, these data indicate that A2 neurons promote both cardiovascular and HPA axis responses to acute stress. Moreover, A2 catecholaminergic neurons may contribute to the potentially deleterious enhancement of sympathetic drive following chronic stress.

  20. Occurrence of FSH, inhibin and other hypothalamic-pituitary-intestinal hormones in normal fertility, subfertility, and tumors of human testes.

    Science.gov (United States)

    Mehta, M K; Garde, S V; Sheth, A R

    1995-01-01

    To compare the distribution of peptide hormones in presumably normal human testicular tissues and specimens exhibiting any of five pathologies. Biopsies from patients having testicular malfunctions were prepared as sections and specifically immunohistochemically stained for inhibin, FSH, serotonin, AUP, and oxytocin. Immunocytochemical studies revealed the presence of various hypophysial-pituitary-intestinal hormones, viz., FSH, inhibin, arginine vasopressin (AVP), calcitonin, serotonin, oxytocin, adrenocorticotropin (ACTH), gastrin, secretin, and somatostatin in human testicular biopsies exhibiting normal spermatogenesis, Sertoli-cell-only syndrome, spermatogenic arrest, Leydig cell hyperplasia, Leydig cell tumor, and seminoma. Intensity of immunostaining for all peptides except FSH was stronger in cases of subfertile as compared to normal testis. Intensity of immunostaining with inhibin was maximum in Leydig cell tumor. These regulatory peptides may be involved in the pathophysiology of the testes.

  1. Hormones and breast cancer: can we use them in ways that could reduce the risk?

    Directory of Open Access Journals (Sweden)

    Khalid Mahmud

    2011-12-01

    Full Text Available Many hormones promote or inhibit breast cancer in different ways. These effects and the mechanisms involved are reviewed in order to suggest a potentially safer use of hormones. Natural estrogens, administered transdermally, and natural progesterone may be the safest combination of female hormones. Increased intake of cruciferous vegetables could provide additional safety by improving 2-hydoxyestrone and diminishing 16 alphahydroxyestrone. Testosterone and dehydroepiandrosterone (DHEA may directly inhibit breast cancer, but could potentially stimulate it by being aromatized into estrogen in the breast. Modest doses with blood level monitoring appear logical. Melatonin and oxytocin are inhibitory to breast and other cancers. Insulin is a growth factor for breast cancer. Managing insulin resistance before the onset of diabetes could reduce the risk. Tri-iodothyronine (T3 has multiple anti-breast cancer effects. Synthroid may not increase T3 levels adequately. Human growth hormone does not appear to increase risk; but it should not be given for performance enhancement.

  2. Intranasal Oxytocin Selectively Modulates Social Perception, Craving, and Approach Behavior in Subjects With Alcohol Use Disorder.

    Science.gov (United States)

    Mitchell, Jennifer M; Arcuni, Peter A; Weinstein, Dawn; Woolley, Josh D

    2016-01-01

    A pharmacotherapy that both improves social abilities and promotes abstinence may be particularly helpful for the treatment of alcohol use disorder. Recent clinical and preclinical evidence suggests that oxytocin has prosocial and antiaddiction effects. We performed a pilot, laboratory-based, preclinical trial of oxytocin in subjects with alcohol abuse (as per Diagnostic and Statistical Manual of Mental Disorders, 4 Edition criteria) to evaluate therapeutic potential and assess tolerability. Social perceptual ability, cue-induced craving, and approach bias for alcohol and appetitive imagery were quantified after intranasal oxytocin and placebo administration to 32 nontreatment-seeking individuals with alcohol abuse in a double-blind, crossover study. Because attachment style can moderate the effects of oxytocin, we also explored whether attachment style moderated oxytocin's effects on our behavioral measures. Oxytocin significantly improved recognition of easier items on a social perception task, but had no significant group-level effect on cue-induced craving. However, oxytocin effects on craving were moderated by attachment anxiety, with oxytocin reducing craving in more anxiously attached individuals and increasing craving in less anxiously attached individuals. Subjects did not display an approach bias to alcohol images on the placebo day, preventing meaningful analysis of this measure. Subjects did display an approach bias to appetitive images on the placebo day, which was significantly reduced by oxytocin administration. No adverse reactions were observed. Intranasal oxytocin has potential to improve social perception, reduce cue-induced alcohol cravings, and reduce appetitive approach bias in subjects with alcohol abuse, and can be safely tolerated in this population. The effects of oxytocin are complex, however, and require further investigation.

  3. Oxytocin Receptor (OXTR Polymorphisms and Attachment in Human Infants

    Directory of Open Access Journals (Sweden)

    Frances S Chen

    2011-08-01

    Full Text Available Ordinary variations in human infants’ attachment behaviors—their proclivity to seek and accept comfort from caregivers—are associated with a wide range of individual differences in psychological functioning in adults. The current investigation examined variation in the oxytocin receptor (OXTR gene as one possible source of these variations in infant attachment. One hundred and seventy-six infants (77 Caucasian, 99 non-Caucasian were classified as securely or insecurely attached based on their behavior in the Strange Situation (Ainsworth et al., 1976. The A allele at OXTR rs2254298 was associated with attachment security in the non-Caucasian infants (p < .005. These findings underscore the importance of oxytocin in the development of human social behavior and support its role in social stress-regulation and the development of trust.

  4. Fluorescent visualization of oxytocin in the hypothalamo-neurohypophysial system

    Directory of Open Access Journals (Sweden)

    Hirofumi eHashimoto

    2014-07-01

    Full Text Available Oxytocin (OXT is well known for its ability to the milk ejection reflex and uterine contraction. It is also involved in several other behaviors, such as anti-nociception, anxiety, feeding, social recognition and stress responses. OXT is synthesized in the magnocellular neurosecretory cells (MNCs in the hypothalamic paraventricular (PVN and the supraoptic nuclei (SON that terminate their axons in the posterior pituitary (PP. We generated transgenic rats that express the OXT and fluorescent protein fusion gene in order to visualize oxytocin in the hypothalamo-neurohypophysial system. In these transgenic rats, fluorescent proteins were observed in the MNCs and axon terminals in the PP. This transgenic rat is a new tool to study the physiological role of OXT in the hypothalamo-neurohypophysial system.

  5. Oxytocin, vasopressin and estrogen receptor gene expression in relation to social recognition in female mice.

    Science.gov (United States)

    Clipperton-Allen, Amy E; Lee, Anna W; Reyes, Anny; Devidze, Nino; Phan, Anna; Pfaff, Donald W; Choleris, Elena

    2012-02-28

    Inter- and intra-species differences in social behavior and recognition-related hormones and receptors suggest that different distribution and/or expression patterns may relate to social recognition. We used qRT-PCR to investigate naturally occurring differences in expression of estrogen receptor-alpha (ERα), ER-beta (ERβ), progesterone receptor (PR), oxytocin (OT) and receptor, and vasopressin (AVP) and receptors in proestrous female mice. Following four 5 min exposures to the same two conspecifics, one was replaced with a novel mouse in the final trial (T5). Gene expression was examined in mice showing high (85-100%) and low (40-60%) social recognition scores (i.e., preferential novel mouse investigation in T5) in eight socially-relevant brain regions. Results supported OT and AVP involvement in social recognition, and suggest that in the medial preoptic area, increased OT and AVP mRNA, together with ERα and ERβ gene activation, relate to improved social recognition. Initial social investigation correlated with ERs, PR and OTR in the dorsolateral septum, suggesting that these receptors may modulate social interest without affecting social recognition. Finally, increased lateral amygdala gene activation in the LR mice may be associated with general learning impairments, while decreased lateral amygdala activity may indicate more efficient cognitive mechanisms in the HR mice. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Estrogen and oxytocin receptors in the canine corpus luteum during pregnancy and parturition

    Directory of Open Access Journals (Sweden)

    Gisele Almeida Lima Veiga

    2015-02-01

    Full Text Available The expression of genes encoding the receptors for estrogen (ERαmRNA and oxytocin (OTRmRNA was studied in the corpus luteum during pregnancy and parturition in dogs. Real-time PCR was performed to quantify the levels of ERαmRNA and OTRmRNA in the corpus luteum of bitches during Early (up to 20 days of gestation, Mid (20 to 40 days and Late Pregnancy (40 to 60 days, and Parturition (first stage of labor. The corpus luteum expressed mRNA for OTR, however ERα mRNA was not detected. There was a reduction of OTR mRNA expression in the corpus luteum from gestational Day 20 onward, which suggests an important role of OTR mRNA in the mechanism of pregnancy recognition in dogs. We concluded that the expression of OTR mRNA in canine corpus luteum vary over time, which support the idea that the sensitivity and response to hormone therapy can vary along the course of pregnancy and labor. Moreover, the canine CL lacks ERα mRNA expression during pregnancy.

  7. Inhaled oxytocin amplifies both vicarious reinforcement and self reinforcement in rhesus macaques (Macaca mulatta).

    Science.gov (United States)

    Chang, Steve W C; Barter, Joseph W; Ebitz, R Becket; Watson, Karli K; Platt, Michael L

    2012-01-17

    People attend not only to their own experiences, but also to the experiences of those around them. Such social awareness profoundly influences human behavior by enabling observational learning, as well as by motivating cooperation, charity, empathy, and spite. Oxytocin (OT), a neurosecretory hormone synthesized by hypothalamic neurons in the mammalian brain, can enhance affiliation or boost exclusion in different species in distinct contexts, belying any simple mechanistic neural model. Here we show that inhaled OT penetrates the CNS and subsequently enhances the sensitivity of rhesus macaques to rewards occurring to others as well as themselves. Roughly 2 h after inhaling OT, monkeys increased the frequency of prosocial choices associated with reward to another monkey when the alternative was to reward no one. OT also increased attention to the recipient monkey as well as the time it took to render such a decision. In contrast, within the first 2 h following inhalation, OT increased selfish choices associated with delivery of reward to self over a reward to the other monkey, without affecting attention or decision latency. Despite the differences in species typical social behavior, exogenous, inhaled OT causally promotes social donation behavior in rhesus monkeys, as it does in more egalitarian and monogamous ones, like prairie voles and humans, when there is no perceived cost to self. These findings potentially implicate shared neural mechanisms.

  8. Oxytocin and vasopressin enhance responsiveness to infant stimuli in adult marmosets.

    Science.gov (United States)

    Taylor, Jack H; French, Jeffrey A

    2015-09-01

    The neuropeptides oxytocin (OT) and arginine-vasopressin (AVP) have been implicated in modulating sex-specific responses to offspring in a variety of uniparental and biparental rodent species. Despite the large body of research in rodents, the effects of these hormones in biparental primates are less understood. Marmoset monkeys (Callithrix jacchus) belong to a clade of primates with a high incidence of biparental care and also synthesize a structurally distinct variant of OT (proline instead of leucine at the 8th amino acid position; Pro(8)-OT). We examined the roles of the OT and AVP systems in the control of responses to infant stimuli in marmoset monkeys. We administered neuropeptide receptor agonists and antagonists to male and female marmosets, and then exposed them to visual and auditory infant-related and control stimuli. Intranasal Pro(8)-OT decreased latencies to respond to infant stimuli in males, and intranasal AVP decreased latencies to respond to infant stimuli in females. Our study is the first to demonstrate that Pro(8)-OT and AVP alter responsiveness to infant stimuli in a biparental New World monkey. Across species, the effects of OT and AVP on parental behavior appear to vary by species-typical caregiving responsibilities in males and females. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Corticotrophin-Releasing Hormone Type 1 Receptor Gene (CRHR1 Variants Predict Posttraumatic Stress Disorder Onset and Course in Pediatric Injury Patients

    Directory of Open Access Journals (Sweden)

    Ananda B. Amstadter

    2011-01-01

    Full Text Available Posttraumatic stress disorder (PTSD is a common and disabling anxiety disorder that may occur in the aftermath of exposure to potentially traumatic life events. PTSD is moderately heritable, but few specific molecular variants accounting for this heritability have been identified. Genes regulating the hypothalamic-pituitary-adrenal (HPA axis, such as corticotrophin-releasing hormone type 1 receptor gene (CRHR1, have been implicated in traumatic-stress related phenotypes but have yet to be studied in relation to PTSD. The present study sought to examine the relation between 9 single nucleotide polymorphisms (SNPs in the CRHR1 gene and posttraumatic stress symptoms in a prospective study of pediatric injury patients (n = 103 who were first assessed in the acute aftermath of their injury at the hospital. Results indicated that multiple SNPs were associated with acute symptoms at a univariate level, and after correction for multiple testing, rs12944712 was significantly related to acute PTSD symptoms. Longitudinal latent growth curve analyses suggest that rs12944712 is also related to both acute symptom level and trajectory of symptoms over time. The present study adds support for the role of CRHR1 in the stress response following potentially traumatic event exposure in youth. It should be noted that the sample size in this study was small, and therefore statistical power was low; following, results from this study should be considered preliminary. Although results are not definitive, the findings from this study warrant future replication studies on how variation in this gene relates to response to traumatic event exposure in youth.

  10. Corticotrophin-releasing hormone type 1 receptor gene (CRHR1) variants predict posttraumatic stress disorder onset and course in pediatric injury patients.

    Science.gov (United States)

    Amstadter, Ananda B; Nugent, Nicole R; Yang, Bao-Zhu; Miller, Alisa; Siburian, Richie; Moorjani, Priya; Haddad, Stephen; Basu, Aditi; Fagerness, Jesen; Saxe, Glenn; Smoller, Jordan W; Koenen, Karestan C

    2011-01-01

    Posttraumatic stress disorder (PTSD) is a common and disabling anxiety disorder that may occur in the aftermath of exposure to potentially traumatic life events. PTSD is moderately heritable, but few specific molecular variants accounting for this heritability have been identified. Genes regulating the hypothalamic-pituitary-adrenal (HPA) axis, such as corticotrophin-releasing hormone type 1 receptor gene (CRHR1), have been implicated in traumatic-stress related phenotypes but have yet to be studied in relation to PTSD. The present study sought to examine the relation between 9 single nucleotide polymorphisms (SNPs) in the CRHR1 gene and posttraumatic stress symptoms in a prospective study of pediatric injury patients (n=103) who were first assessed in the acute aftermath of their injury at the hospital. Results indicated that multiple SNPs were associated with acute symptoms at a univariate level, and after correction for multiple testing, rs12944712 was significantly related to acute PTSD symptoms. Longitudinal latent growth curve analyses suggest that rs12944712 is also related to both acute symptom level and trajectory of symptoms over time. The present study adds support for the role of CRHR1 in the stress response following potentially traumatic event exposure in youth. It should be noted that the sample size in this study was small, and therefore statistical power was low; following, results from this study should be considered preliminary. Although results are not definitive, the findings from this study warrant future replication studies on how variation in this gene relates to response to traumatic event exposure in youth.

  11. Oxytocin mediates copulation-induced hypoalgesia of male rats.

    Science.gov (United States)

    Futagami, Hiroko; Sakuma, Yasuo; Kondo, Yasuhiko

    2016-04-08

    Copulatory behavior has been reported to raise the pain threshold in male rats. In this study, we examined the effect of copulatory behavior with or without ejaculation on pain threshold measured by electrical shock via an electrode attached to the tail. It was demonstrated that ejaculation is not necessary to raise the pain threshold in male rats. In addition, we examined whether oxytocin, a hypothalamic neuropeptide, was involved in copulation-induced hypoalgesia. Sexually experienced males were subjected to stereotaxic implantation of a guide cannula targeting the lateral ventricle. After the recovery period, half of the males were intracerebroventricularly treated with an oxytocin antagonist (OTA, 100ng d(CH2)51,Tyr(Me)2,Thr4, Orn8,Tyr-NH29]-vasotocin/1μL saline) and the remaining half were administered saline without anesthesia. Fifteen minutes later, half of each group were given sexual behavior with receptive females. We found no effect of OTA on sexual activity. Immediately after ejaculation, pain threshold was measured. While raised pain threshold was observed after sexual behavior in saline-treated males, no change in pain threshold was found in OTA-treated males even after copulation. The results suggest that central oxytocin mediates copulation-induced hypoalgesia in male rats. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. The potential for oxytocin (OT) to prevent breast cancer: a hypothesis.

    Science.gov (United States)

    Murrell, T G

    1995-08-01

    This hypothesis proposes that carcinogens in the breast are generated by the action of superoxide free radicals released when acinal gland distension, under the influence of unopposed prolactin, causes microvessel ischaemia. Inadequate nipple care in the at-risk years leads to ductal obstruction preventing the elimination of carcinogens from the breast. The regular production of oxytocin (OT) from nipple stimulation would cause contraction of the myoepithelial cells, relieving acinal gland distension and aiding the active elimination of carcinogenic fluid from the breast. Mechanical breast pump stimulation causes an increase in plasma OT levels in the luteal but not in the follicular phase of the menstrual cycle. OT production upon nipple stimulation in the luteal phase of premenopausal, non-lactating women may be protective against the high rates of mitotic breast cell division noted at this time via the potential to block the effect of oestrogen. The epidemiology of breast cancer suggests that lengthy lactation time is beneficial. Sexual activity in nulliparous women also protects and OT levels have been shown to rise with orgasm in women and in men. OT systems in the brain are intricately linked to oestrogen and progesterone levels, and it is possible that these hormones may modify the OT secretory response both centrally and through an effect on the sensitivity of the breast. OT production with nipple care and in sex and lactation, and the reduction in cycling ovarian hormones that occurs with pregnancy, may all be important preventative factors in the development of breast cancer both pre- and post-menopausally.

  13. [Association between oxytocin augmentation intervals and the risk of postpartum haemorrhage].

    Science.gov (United States)

    Loscul, C; Chantry, A-A; Caubit, L; Deneux-Tharaux, C; Goffinet, F; Le Ray, C

    2016-09-01

    To study the association between the duration of oxytocin augmentation intervals and the risk of postpartum haemorrhage (PPH) among primiparous women in spontaneous labour. Retrospective cohort including primiparous women in spontaneous labour who received oxytocin during labour (n=454). Oxytocin augmentation intervals were dichotomized in intervalsoxytocin augmentation intervals. The association between oxytocin augmentation intervals and PPH was analyzed using univariate and multivariate analysis. Oxytocin augmentation intervals were shorter than 20minutes for 43.8% of the study population. The rate of PPH was higher (9.1% vs 3.5%; P=0.014), and the use of sulprostone was more frequent (6.5% vs 3.5%; P=0.013) if oxytocin augmentation intervals were shorter than 20minutes in comparison with intervals≥20minutes. The association between oxytocin augmentation intervals and PPH remains significant after adjustment on other PPH risk factors (adjusted OR=3.48, 95% CI [1.45-8.34]). The rate of adverse neonatal issue, defined by arterial pH at birth≤7.10 and/or 5minutes score d'Apgar≤7, was higher if oxytocin augmentation intervals wereoxytocin with augmentation intervals shorter than 20minutes. Copyright © 2016. Published by Elsevier Masson SAS.

  14. Use of oxytocin during Caesarean section at Princess Marina Hospital, Botswana: An audit of clinical practice

    Directory of Open Access Journals (Sweden)

    Billy M. Tsima

    2013-02-01

    Full Text Available Background: Oxytocin is widely used for the prevention of postpartum haemorrhage. In the setting of Caesarean section (CS, the dosage and mode of administrating oxytocin differs according to different guidelines. Inappropriate oxytocin doses have been identified ascontributory to some cases of maternal deaths. The main aim of this study was to audit the current standard of clinical practice with regard to the use of oxytocin during CS at a referral hospital in Botswana.Methods: A clinical audit of pregnant women having CS and given oxytocin at the time of the operation was conducted over a period of three months. Data included indications for CS, oxytocin dose regimen, prescribing clinician’s designation, type of anaesthesia for the CS and estimated blood loss.Results: A total of 139 case records were included. The commonest dose was 20 IU infusion (31.7%. The potentially dangerous regimen of 10 IU intravenous bolus of oxytocin was used in 12.9% of CS. Further doses were utilized in 57 patients (41%. The top three indications forCS were fetal distress (36 patients, 24.5%, dystocia (32 patients, 21.8% and a previous CS (25 patients, 17.0%. Estimated blood loss ranged from 50 mL – 2000 mL.Conclusion: The use of oxytocin during CS in the local setting does not follow recommended practice. This has potentially harmful consequences. Education and guidance through evidencebased national guidelines could help alleviate the problem.

  15. Lack of association between human plasma oxytocin and interpersonal trust in a Prisoner's Dilemma paradigm.

    Directory of Open Access Journals (Sweden)

    James C Christensen

    Full Text Available Expanding interest in oxytocin, particularly the role of endogenous oxytocin in human social behavior, has created a pressing need for replication of results and verification of assay methods. In this study, we sought to replicate and extend previous results correlating plasma oxytocin with trust and trustworthy behavior. As a necessary first step, the two most commonly used commercial assays were compared in human plasma via the addition of a known quantity of exogenous oxytocin, with and without sample extraction. Plasma sample extraction was found to be critical in obtaining repeatable concentrations of oxytocin. In the subsequent trust experiment, twelve samples in duplicate, from each of 82 participants, were collected over approximately six hours during the performance of a Prisoner's Dilemma task paradigm that stressed human interpersonal trust. We found no significant relationship between plasma oxytocin concentrations and trusting or trustworthy behavior. In light of these findings, previous published work that used oxytocin immunoassays without sample extraction should be reexamined and future research exploring links between endogenous human oxytocin and trust or social behavior should proceed with careful consideration of methods and appropriate biofluids for analysis.

  16. Working hard for oneself or others: Effects of oxytocin on reward motivation in social anxiety disorder.

    Science.gov (United States)

    Fang, Angela; Treadway, Michael T; Hofmann, Stefan G

    2017-07-01

    There is some evidence to suggest that oxytocin promotes social behavior, especially for disorders characterized by social dysfunction, such as social anxiety disorder (SAD). The goal of this study was to examine the effect of oxytocin on reward motivation in SAD. We tested whether oxytocin promotes prosocial, or antisocial, self-directed decisions, and whether its effects depended on social anxiety severity and attachment. Fifty-two males with SAD received 24 international units of oxytocin or placebo, and completed a reward motivation task that measured willingness to work for self vs. other monetary rewards. Although there was no main drug effect, social anxiety severity moderated the effect of oxytocin. Less socially anxious individuals who received oxytocin worked harder for other vs. own rewards, compared to high socially anxious individuals. Attachment did not moderate this effect. Among people with SAD, oxytocin enhances prosocial behaviors in individuals with relatively lower levels of social anxiety. National Institutes of Health ClinicalTrials.gov Registry #NCT01856530. https://clinicaltrials.gov/ct2/show/NCT01856530?term=oxytocin+pro-social&rank=2. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Relations between plasma oxytocin and cortisol: The stress buffering role of social support

    Directory of Open Access Journals (Sweden)

    Robyn J. McQuaid

    2016-06-01

    Full Text Available Stress responses in humans can be attenuated by exogenous oxytocin administration, and these stress-buffering properties may be moderated by social factors. Yet, the influence of acute stressors on circulating endogenous oxytocin levels have been inconsistent, and limited information is available concerning the influence of social support in moderating this relationship. In the current investigation, undergraduate women (N = 67 were assessed in the Trier Social Stress Test (TSST with either social support available from a close female friend or no social support being available. An additional set of women served as controls. The TSST elicited marked elevations of state anxiety and negative emotions, which were largely attenuated among women who received social support. Furthermore, baseline oxytocin levels were inversely related to women's general feelings of distrust, as well as basal plasma cortisol levels. Despite these associations, oxytocin levels were unaffected by the TSST, and this was the case irrespective of oral contraceptive use or estrogen levels. In contrast, plasma cortisol elevations were elicited by the psychosocial stressor, but only in women using oral contraceptives, an effect that was prevented when social support was available. Taken together, these data provisionally suggest that changes in plasma oxytocin might not accompany the stress attenuating effects of social support on cortisol levels. Moreover, as plasma oxytocin might not reliably reflect brain oxytocin levels, the linkage between oxytocin and prosocial behaviors remains tenuous.

  18. Effects of oxytocin on fertility of red sokoto goats treated with ...

    African Journals Online (AJOL)

    The objective of this study was to evaluate the effects of oxytocin (OX) administration on conception rates in does. Red Sokoto (RS) does (n = 38) were equally allocated into 2 groups; I: does treated with prostaglandin plus normal saline (PGNS) and II: does treated with prostaglandin plus oxytocin (PGOX). Does were ...

  19. Hypooxytocinaemia in obese Zucker rats relates to oxytocin degradation in liver and adipose tissue

    Czech Academy of Sciences Publication Activity Database

    Gajdošechová, L.; Kršková, K.; Segarra, A. B.; Špolcová, Andrea; Suski, M.; Olszanecki, R.; Zórad, S.

    2014-01-01

    Roč. 220, č. 3 (2014), s. 333-343 ISSN 0022-0795 Institutional support: RVO:61388963 Keywords : oxytocin * obesity * insulin resistance * oxytocinase * oxytocin receptor Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.718, year: 2014

  20. Nasal Oxytocin for Social Deficits in Childhood Autism: A Randomized Controlled Trial

    Science.gov (United States)

    Dadds, Mark R.; MacDonald, Elayne; Cauchi, Avril; Williams, Katrina; Levy, Florence; Brennan, John

    2014-01-01

    The last two decades have witnessed a surge in research investigating the application of oxytocin as a method of enhancing social behaviour in humans. Preliminary evidence suggests oxytocin may have potential as an intervention for autism. We evaluated a 5-day "live-in" intervention using a double-blind randomized control trial. 38 male…

  1. Intrapartum synthetic oxytocin reduce the expression of primitive reflexes associated with breastfeeding.

    Science.gov (United States)

    Marín Gabriel, Miguel A; Olza Fernández, Ibone; Malalana Martínez, Ana M; González Armengod, Carmen; Costarelli, Valeria; Millán Santos, Isabel; Fernández-Cañadas Morillo, Aurora; Pérez Riveiro, Pilar; López Sánchez, Francisco; García Murillo, Lourdes

    2015-05-01

    Several synthetic peptide manipulations during the time surrounding birth can alter the specific neurohormonal status in the newborn brain. This study is aimed at assessing whether intrapartum oxytocin administration has any effect on primitive neonatal reflexes and determining whether such an effect is dose-dependent. A cohort prospective study was conducted at a tertiary hospital. Mother-infant dyads who received intrapartum oxytocin (n=53) were compared with mother-infant dyads who did not receive intrapartum oxytocin (n=45). Primitive neonatal reflexes (endogenous, antigravity, motor, and rhythmic reflexes) were quantified by analyzing videotaped breastfeeding sessions in a biological nurturing position. Two observers blind to the group assignment and the oxytocin dose analyzed the videotapes and assesed the newborn's state of consciousness according to the Brazelton scale. The release of all rhythmic reflexes (p=0.01), the antigravity reflex (p=0.04), and total primitive neonatal reflexes (p=0.02) in the group exposed to oxytocin was lower than in the group not exposed to oxytocin. No correlations were observed between the dose of oxytocin administered and the percentage of primitive neonatal reflexes released (r=0.03; p=0.82). Intrapartum oxytocin administration might inhibit the expression of several primitive neonatal reflexes associated with breastfeeding. This correlation does not seem to be dose-dependent.

  2. Neonatal oxytocin manipulations have long-lasting, sexually dimorphic effects on vasopressin receptors

    OpenAIRE

    Bales, KL; Plotsky, PM; Young, LJ; Lim, MM; Grotte, N; Ferrer, E; Carter, CS

    2007-01-01

    Developmental exposure to oxytocin (OT) or oxytocin antagonists (OTAs) has been shown to cause long-lasting and often sexually dimorphic effects on social behaviors in prairie voles (Microtus ochrogaster). Because regulation of social behavior in monogamous mammals involves central receptors for OT, arginine vasopressin (AVP), and dopamine, we examined the hypothesis that the lon...

  3. Oxytocin is associated with PTSD's anxious arousal symptoms in Chinese male earthquake survivors

    Directory of Open Access Journals (Sweden)

    Chengqi Cao

    2014-12-01

    Full Text Available Background: Posttraumatic stress disorder (PTSD is a complex and severe mental disorder triggered by exposure to an extraordinarily traumatic event. Human and animal studies have implied the functional role of the oxytocin system in the development of PTSD (Cochran, Fallon, Hill, & Frazier, 2013; Koch et al., 2014; Olff, 2012. Specification of the role of the oxytocin system in the emergence and progression of PTSD symptomatology would provide evidence to inform both theory and clinical practice. Methods: This study examined the association between oxytocin serum levels and PTSD symptoms. A total of 106 Chinese male adults who suffered from the deadly 2008 Wenchuan earthquake participated in this study. PTSD symptoms were measured with PTSD Checklist for DSM-5 (PCL-5, and serum oxytocin level was determined with ELISA oxytocin kits. Results: The mean score on the PCL-5 was 19.30 (SD=14.50, range: 1–65 in this sample. The mean oxytocin level was 101.59 pg/ml (SD=55.89, range: 31.50–286.71. The results indicated that although the oxytocin was not associated with total PTSD symptoms, it was associated with PTSD's anxious arousal symptoms. Conclusion: These findings support that the oxytocin may play an important functional role in the development of PTSD and contribute to the extant knowledge on the genetic basis of the PTSD symptoms.

  4. Radioimmunoassay measurement of plasma oxytocin and vasopressin in cows during machine milking

    Energy Technology Data Exchange (ETDEWEB)

    Landgraf, R; Wehowsky, G; Schulz, J; Schulze, H; Bothur, D [Forschungsinstitut fuer Koerperkultur und Sport, Leipzig (German Democratic Republic); Karl-Marx-Universitaet, Leipzig (German Democratic Republic). Sektion Tierproduktion und Veterinaermedizin)

    1982-07-01

    The response of plasma oxytocin and vasopressin to machine milking in cows was studied by radioimmunoassay. Depending on the method of machine milking used, plasma oxytocin increased to a greater or lesser degree after teat cup application. Plasma vasopressin was not affected by the milking procedures.

  5. Oxytocin eliminates the own-race bias in face recognition memory.

    Science.gov (United States)

    Blandón-Gitlin, Iris; Pezdek, Kathy; Saldivar, Sesar; Steelman, Erin

    2014-09-11

    The neuropeptide Oxytocin influences a number of social behaviors, including processing of faces. We examined whether Oxytocin facilitates the processing of out-group faces and reduce the own-race bias (ORB). The ORB is a robust phenomenon characterized by poor recognition memory of other-race faces compared to the same-race faces. In Experiment 1, participants received intranasal solutions of Oxytocin or placebo prior to viewing White and Black faces. On a subsequent recognition test, whereas in the placebo condition the same-race faces were better recognized than other-race faces, in the Oxytocin condition Black and White faces were equally well recognized, effectively eliminating the ORB. In Experiment 2, Oxytocin was administered after the study phase. The ORB resulted, but Oxytocin did not significantly reduce the effect. This study is the first to show that Oxytocin can enhance face memory of out-group members and underscore the importance of social encoding mechanisms underlying the own-race bias. This article is part of a Special Issue entitled Oxytocin and Social Behav. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Oxytocin effects on complex brain networks are moderated by experiences of maternal love withdrawal.

    Science.gov (United States)

    Riem, Madelon M E; van IJzendoorn, Marinus H; Tops, Mattie; Boksem, Maarten A S; Rombouts, Serge A R B; Bakermans-Kranenburg, Marian J

    2013-10-01

    The neuropeptide oxytocin has been implicated in a variety of social processes. However, recent studies indicate that oxytocin does not enhance prosocial behavior in all people in all circumstances. Here, we investigate effects of intranasal oxytocin administration on intrinsic functional brain connectivity with resting state functional magnetic resonance imaging. Participants were 42 women who received a nasal spray containing either 16 IU of oxytocin or a placebo and reported how often their mother used love withdrawal as a disciplinary strategy involving withholding love and affection after a failure or misbehavior. We found that oxytocin changes functional connectivity between the posterior cingulate cortex (PCC) and the brainstem. In the oxytocin group there was a positive connectivity between these regions, whereas the placebo group showed negative connectivity. In addition, oxytocin induced functional connectivity changes between the PCC, the cerebellum and the postcentral gyrus, but only for those participants who experienced low levels of maternal love withdrawal. We speculate that oxytocin enhances prosocial behavior by influencing complex brain networks involved in self-referential processing and affectionate touch, most prominently in individuals with supportive family backgrounds. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

  7. Can oxytocin augmentation modify the risk of epidural analgesia by maternal age in cesarean sections?

    Science.gov (United States)

    Rossen, Janne; Klungsøyr, Kari; Albrechtsen, Susanne; Løkkegård, Ellen; Rasmussen, Steen; Bergholt, Thomas; Skjeldestad, Finn E

    2018-03-07

    Maternal age is an established risk factor for cesarean section; epidural analgesia and oxytocin augmentation may modify this association. We investigated the effects and interactions of oxytocin augmentation, epidural analgesia and maternal age on the risk of cesarean section. In all, 416 386 nulliparous women with spontaneous onset of labor, ≥37 weeks of gestation and singleton infants with a cephalic presentation during 2000-2011 from Norway and Denmark were included [Ten-group classification system (Robson) group 1]. In this case-control study the main exposure was maternal age; epidural analgesia, oxytocin augmentation, birthweight and time period were explanatory variables. Chi-square test and logistic regression were used to estimate associations and interactions. The cesarean section rate increased consistently with advancing maternal age, both overall and in strata of epidural analgesia and oxytocin augmentation. We observed strong interactions between maternal age, oxytocin augmentation and epidural analgesia for the risk of cesarean section. Women with epidural analgesia generally had a reduced adjusted odds ratio when oxytocin was used compared with when it was not used. In Norway, this applied to all maternal age groups but in Denmark only for women ≥30 years. Among women without epidural, oxytocin augmentation was associated with an increased odds ratio for cesarean section in Denmark, whereas no difference was observed in Norway. Oxytocin augmentation in nulliparous women with epidural analgesia is associated with a reduced risk of cesarean section in labor with spontaneous onset. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

  8. A statistical method to calculate blood contamination in the measurement of salivary hormones in healthy women.

    Science.gov (United States)

    Behr, Guilherme A; Patel, Jay P; Coote, Marg; Moreira, Jose C F; Gelain, Daniel P; Steiner, Meir; Frey, Benicio N

    2017-05-01

    Previous studies have reported that salivary concentrations of certain hormones correlate with their respective serum levels. However, most of these studies did not control for potential blood contamination in saliva. In the present study we developed a statistical method to test the amount of blood contamination that needs to be avoided in saliva samples for the following hormones: cortisol, estradiol, progesterone, testosterone and oxytocin. Saliva and serum samples were collected from 38 healthy, medication-free women (mean age=33.8±7.3yr.; range=19-45). Serum and salivary hormonal levels and the amount of transferrin in saliva samples were determined using enzyme immunoassays. Salivary transferrin levels did not correlate with salivary cortisol or estradiol (up to 3mg/dl), but they were positively correlated with salivary testosterone, progesterone and oxytocin (phormones in order to determine the level of blood contamination that might affect specific hormonal salivary concentrations. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  9. The effects of oxytocin on social cognition in borderline personality disorder.

    Science.gov (United States)

    Servan, A; Brunelin, J; Poulet, E

    2018-02-01

    Deficits in social cognition and interpersonal difficulties are key features in borderline personality disorder. Social cognition refers to the function of perceiving and adequately dealing with social signals, leading to the establishment and maintenance of healthy and positive social relationships. Evidence suggests that oxytocin (OT) may improve social cognition and human social behavior. Recently, several studies have highlighted the beneficial effects of oxytocin in several psychiatric conditions involving social cognition deficits such as schizophrenia, autism or social phobia. However, despite growing interest, the effects of oxytocin in patients with borderline personality disorder are far from being clearly demonstrated. The objective of this work was to review and discuss studies investigating the interest of oxytocin in alleviating social cognition deficits in patients with borderline personality disorder (recognition of emotion, trust and cooperation, affective and cognitive empathy, emotional expression and social problem-solving). A systematic review of the literature was conducted up to September 31, 2016 on the Pubmed, Science direct, Medline and Scopus databases using "borderline personality disorder" and "oxytocin" as keywords. To be included, studies were to include patients with borderline personality disorder; to investigate social cognition and to investigate the effect of oxytocin on social cognition in patients with TPB. The initial search yielded 52 articles. Among them, 11 studies were selected according to the PRISMA criteria. The effect of oxytocin on social cognition in patients with borderline personality disorder was mainly investigated in relation to recognition of emotions and trust and cooperation. We did not find any studies investigating the effect of oxytocin on affective and cognitive empathy, emotional expression or social problem-solving abilities. In patients with borderline personality disorder, oxytocin had a beneficial

  10. Imaging oxytocin x dopamine interactions: An epistasis effect of CD38 and COMT gene variants influences the impact of oxytocin on amygdala activation to social stimuli

    Directory of Open Access Journals (Sweden)

    Carina eSauer

    2013-04-01

    Full Text Available Although oxytocin (OT has become a major target for the investigation of positive social processes, it can be assumed that it exerts its effects in concert with other neurotransmitters. One candidate for such an interaction is dopamine (DA. For both systems, genetic variants have been identified that influence the availability of the particular substance. A variant of the gene coding for the transmembrane protein CD38 (rs3796863, which is engaged in OT secretion, has been associated with OT plasma level. The common catechol-O-methyltransferase (COMT val158met polymorphism is known to influence COMT activity and therefore the degradation of DA. The present study aimed to investigate OTxDA interactions in the context of an OT challenge study. Hence, we tested the influence of the above mentioned genetic variants and their interaction on the activation of different brain regions (amygdala, VTA, ventral striatum and fusiform gyrus during the presentation of social stimuli. In a pharmacological cross-over design 55 participants were investigated under OT and placebo (PLA by means of fMRI.Brain imaging results revealed no significant effects for VTA or ventral striatum. Regarding the fusiform gyrus, we could not find any effects apart from those already described in (Sauer et al., 2012. Analyses of amygdala activation resulted in no gene main effect, no gene x substance interaction but a significant gene x gene x substance interaction. While under PLA the effect of CD38 on bilateral amygdala activation to social stimuli was modulated by the COMT genotype, no such epistasis effect was found under OT. Our results provide evidence for an OTxDA interaction during responses to social stimuli. We postulate that the effect of central OT secretion on amygdala response is modulated by the availability of DA. Therefore, for an understanding of the effect of social hormones on social behavior, interactions of OT with other transmitter systems have to be taken

  11. Consequence of oxytocin injections on minerals concentration in Sahiwal cow milk

    International Nuclear Information System (INIS)

    Hameed, A.; Anjum, F.M.; Zahoor, T.; Jamil, A.

    2010-01-01

    The major objective of this study was to find out the consequence of exogenous administration of oxytocin to Sahiwal cow, local breed of Pakistan (to enhance milk let down) on mineral composition. Milk samples were collected from two groups of eight animals under controlled atmosphere and feeding input. The analysis of fodder and feed samples were also carried out to support this study. Means of macro and micro minerals of fodder and feed samples were determined. One group of Sahiwal cows was subjected to intramuscular injection of oxytocin (20 IU). The milk obtained from oxytocin injected animals possessed significantly higher sodium and chloride with increment in ash content. Lactose content decreased by 0.39% and ash content increased by 0.08% in milk treated with oxytocin injections. Oxytocin administration increased the level of Na (19.74%), Cl (9.39%) and Cu (146.89%) while K content decreased (10.06%). (author)

  12. Oxytocin increases extrapancreatic glucagon secretion and glucose production in pancreatectomized dogs

    International Nuclear Information System (INIS)

    Altszuler, N.; Puma, F.; Winkler, B.; Fontan, N.; Saudek, C.D.

    1986-01-01

    Infusion of oxytocin into normal dogs increases plasma levels of insulin and glucagon and glucose production and uptake. To determine whether infused oxytocin also increases glucagon secretion from extrapancreatic sites, pancreatectomized dogs, off insulin of 18 hr, were infused with oxytocin and plasma glucagon, and glucose production and uptake were measured using the [6- 3 H]glucose primer-infusion technique. The diabetic dogs, in the control period, had elevated plasma glucose and glucagon levels, an increased rate of glucose production, and a relative decrease in glucose uptake (decreased clearance). Infusion of oxytocin (500 μU/kg/min) caused a rise in plasma glucagon and glucose levels, increased glucose production, and further decreased glucose clearance. it is concluded that oxytocin can stimulate secretion of extrapancreatic glucagon, which contributes to the increased glucose production

  13. Preventing PTSD with oxytocin: effects of oxytocin administration on fear neurocircuitry and PTSD symptom development in recently trauma-exposed individuals

    NARCIS (Netherlands)

    Frijling, Jessie L.

    2017-01-01

    Background: Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder which develops in approximately 10% of trauma-exposed individuals. Currently, there are few early preventive interventions available for PTSD. Intranasal oxytocin administration early posttrauma may prevent PTSD

  14. Plasma oxytocin concentrations during late pregnancy and parturition in the dog.

    Science.gov (United States)

    Klarenbeek, M; Okkens, A C; Kooistra, H S; Mol, J A; M M Bevers; Taverne, M A M

    2007-11-01

    While oxytocin is widely used in the treatment of dystocia in dogs, there is little information about its secretion before and during normal unassisted whelping. We therefore measured plasma oxytocin concentrations during late pregnancy and the expulsive stage of parturition. Blood samples were collected from eight dogs at 3-min intervals during a 42-min period between the 2nd and 14th day before whelping and during parturition after the birth of 1-3 pups. The litters consisted of 5-15 pups and the progression of the expulsive stage was linear and nearly parallel in the eight bitches. The overall mean (+/-S.D.) plasma oxytocin concentration during late pregnancy was 3.6+/-2.1pg/ml. Mean values in individual dogs ranged from 1.2 to 7.4 pg/ml, but the intra-animal variation was rather small. During the expulsive stage the overall mean (+/-S.D.) plasma oxytocin concentration was 12.9+/-13.9 pg/ml, with mean values in individual dogs ranging from 3.5 to 46 pg/ml. The mean area under the oxytocin curve for parturient dogs was significantly higher (Pdogs. During the expulsive stage, the peak plasma oxytocin level in individual dogs ranged between 10 and 117 pg/ml. In six of the eight dogs a pup was born during blood collection and in five of these animals the plasma oxytocin concentration increased temporarily during periods of abdominal straining and expulsion. However, straining efforts and expulsion were not consistently associated with a rise in the circulating oxytocin level. It is concluded that in the dog plasma oxytocin levels are higher and more variable during the expulsive stage of parturition than during late pregnancy. Interrelationships between the secretion pattern of oxytocin, the level of uterine contractility, and the progress of fetal expulsion in dogs need further exploration.

  15. Postprandial oxytocin secretion is associated with severity of anxiety and depressive symptoms in anorexia nervosa.

    Science.gov (United States)

    Lawson, Elizabeth A; Holsen, Laura M; Santin, McKale; DeSanti, Rebecca; Meenaghan, Erinne; Eddy, Kamryn T; Herzog, David B; Goldstein, Jill M; Klibanski, Anne

    2013-05-01

    Anorexia nervosa, a psychiatric disorder characterized by self-induced starvation, is associated with endocrine dysfunction and comorbid anxiety and depression. Animal data suggest that oxytocin may have anxiolytic and antidepressant effects. We have reported increased postprandial oxytocin levels in women with active anorexia nervosa and decreased levels in weight-recovered women with anorexia nervosa compared to healthy controls. A meal may represent a significant source of stress in patients with disordered eating. We therefore investigated the association between postprandial oxytocin secretion and symptoms of anxiety and depression in anorexia nervosa. We performed a cross-sectional study of 35 women (13 women with active anorexia nervosa, 9 with weight-recovered anorexia nervosa, and 13 healthy controls). Anorexia nervosa was diagnosed according to DSM-IV-TR criteria. Serum oxytocin and cortisol and plasma leptin levels were measured fasting and 30, 60, and 120 minutes after a standardized mixed meal. The area under the curve (AUC) and, for oxytocin, postprandial nadir and peak levels were determined. Anxiety and depressive symptoms were assessed using the Spielberger State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory II (BDI-II). The study was conducted from January 2009 to March 2011. In women with anorexia nervosa, oxytocin AUC and postprandial nadir and peak levels were positively associated with STAI trait and STAI premeal and postmeal state scores. Oxytocin AUC and nadir levels were positively associated with BDI-II scores. After controlling for cortisol AUC, all of the relationships remained significant. After controlling for leptin AUC, most of the relationships remained significant. Oxytocin secretion explained up to 51% of the variance in STAI trait and 24% of the variance in BDI-II scores. Abnormal postprandial oxytocin secretion in women with anorexia nervosa is associated with increased symptoms of anxiety and depression. This

  16. Oxytocin differently regulates pressor responses to stress in WKY and SHR rats: the role of central oxytocin and V1a receptors.

    Science.gov (United States)

    Wsol, A; Szczepanska-Sadowska, E; Kowalewski, S; Puchalska, L; Cudnoch-Jedrzejewska, A

    2014-01-01

    The role of central oxytocin in the regulation of cardiovascular parameters under resting conditions and during acute stress was investigated in male normotensive Wistar-Kyoto (WKY; n = 40) and spontaneously hypertensive rats (SHR; n = 28). In Experiment 1, mean arterial blood pressure (MABP) and heart rate (HR) were recorded in WKY and SHR rats at rest and after an air-jet stressor during intracerebroventricular (ICV) infusions of vehicle, oxytocin or oxytocin receptor (OTR) antagonist. In Experiment 2, the effects of vehicle, oxytocin and OTR antagonist were determined in WKY rats after prior administration of a V1a vasopressin receptor (V1aR) antagonist. Resting MABP and HR were not affected by any of the ICV infusions either in WKY or in SHR rats. In control experiments (vehicle), the pressor response to stress was significantly higher in SHR. Oxytocin enhanced the pressor response to stress in the WKY rats but reduced it in SHR. During V1aR blockade, oxytocin infusion entirely abolished the pressor response to stress in WKY rats. Combined blockade of V1aR and OTR elicited a significantly greater MABP response to stress than infusion of V1a antagonist and vehicle. This study reveals significant differences in the regulation of blood pressure in WKY and SHR rats during alarming stress. Specifically, the augmentation of the pressor response to stress by exogenous oxytocin in WKY rats is caused by its interaction with V1aR, and endogenous oxytocin regulates the magnitude of the pressor response to stress in WKY rats by simultaneous interaction with OTR and V1aR.

  17. Hyperresponsiveness of hypothalamic-pituitary-adrenal axis to combined dexamethasone/corticotropin-releasing hormone challenge in female borderline personality disorder subjects with a history of sustained childhood abuse

    NARCIS (Netherlands)

    Rinne, Thomas; de Kloet, E. Ronald; Wouters, Luuk; Goekoop, Jaap G.; DeRijk, Roel H.; van den Brink, Wim

    2002-01-01

    Background: High coincidence of childhood abuse, major depressive disorder (MDD), and posttraumatic stress disorder (PTSD) has been reported in patients with borderline personality disorder (BPD). Animals exposed to early trauma show increased stress-induced hypothalamic-pituitary-adrenal (HPA) axis

  18. Association between genetic variation in the oxytocin receptor gene and emotional withdrawal, but not between oxytocin pathway genes and diagnosis in psychotic disorders.

    Directory of Open Access Journals (Sweden)

    Marit eHaram

    2015-01-01

    Full Text Available Social dysfunction is common in patients with psychotic disorders. Oxytocin is a neuropeptide with a central role in social behaviour. This study aims to explore the relationship between oxytocin pathway genes and symptoms related to social dysfunction in patients with psychotic disorders. We performed association analyses between four oxytocin pathway genes (OXT, OXTR, AVP, CD38 and four areas of social behaviour-related psychopathology as measured by Positive and Negative Syndrome Scale (PANSS. For this purpose, we used both a polygenic risk score (PGRS and single OXTR candidate SNPs previously reported in the literature (rs53576, rs237902, rs2254298. A total of 734 subjects with DSM-IV psychotic spectrum disorders and 420 healthy controls were included. Oxytocin pathway PGRSs were calculated based on the independent Psychiatric Genomics Consortium study sample. There was a significant association between symptom of Emotional Withdrawal and the previously reported OXTR risk allele A in rs53576. No significant associations between oxytocin pathway gene variants and a diagnosis of psychotic disorder were found. Our findings indicate that while oxytocin pathway genes do not appear to contribute to the susceptibility to psychotic disorders, variations in the OXTR gene might play a role in the development of impaired social behaviour.

  19. Hormones and absence epilepsy

    NARCIS (Netherlands)

    Luijtelaar, E.L.J.M. van; Tolmacheva, E.A.; Budziszewska, B.; Stein, J.

    2017-01-01

    Hormones have an extremely large impact on seizures and epilepsy. Stress and stress hormones are known to reinforce seizure expression, and gonadal hormones affect the number of seizures and even the seizure type. Moreover, hormonal concentrations change drastically over an individual's lifetime,

  20. Hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes: sex differences in regulation of stress responsivity.

    Science.gov (United States)

    Oyola, Mario G; Handa, Robert J

    2017-09-01

    Gonadal hormones play a key role in the establishment, activation, and regulation of the hypothalamic-pituitary-adrenal (HPA) axis. By influencing the response and sensitivity to releasing factors, neurotransmitters, and hormones, gonadal steroids help orchestrate the gain of the HPA axis to fine-tune the levels of stress hormones in the general circulation. From early life to adulthood, gonadal steroids can differentially affect the HPA axis, resulting in sex differences in the responsivity of this axis. The HPA axis influences many physiological functions making an organism's response to changes in the environment appropriate for its reproductive status. Although the acute HPA response to stressors is a beneficial response, constant activation of this circuitry by chronic or traumatic stressful episodes may lead to a dysregulation of the HPA axis and cause pathology. Compared to males, female mice and rats show a more robust HPA axis response, as a result of circulating estradiol levels which elevate stress hormone levels during non-threatening situations, and during and after stressors. Fluctuating levels of gonadal steroids in females across the estrous cycle are a major factor contributing to sex differences in the robustness of HPA activity in females compared to males. Moreover, gonadal steroids may also contribute to epigenetic and organizational influences on the HPA axis even before puberty. Correspondingly, crosstalk between the hypothalamic-pituitary-gonadal (HPG) and HPA axes could lead to abnormalities of stress responses. In humans, a dysregulated stress response is one of the most common symptoms seen across many neuropsychiatric disorders, and as a result, such interactions may exacerbate peripheral pathologies. In this review, we discuss the HPA and HPG axes and review how gonadal steroids interact with the HPA axis to regulate the stress circuitry during all stages in life.

  1. Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity

    Science.gov (United States)

    Oyola, Mario G.; Handa, Robert J.

    2018-01-01

    Gonadal hormones play a key role in the establishment, activation, and regulation of the hypothalamic–pituitary–adrenal (HPA) axis. By influencing the response and sensitivity to releasing factors, neurotransmitters, and hormones, gonadal steroids help orche