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

PubMed

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.

Oxytocin and social functioning

PubMed Central

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 potential therapeutic option for individuals with social anxiety. Animal research both in nonprimates and primates supports oxytocin's role in facilitation of prosocial behaviors and its anxiolytic effects. Human studies indicate significant associations between social anxiety and oxytocin receptor gene alleles, as well as social anxiety and oxytocin plasma levels. In addition, intranasal administration of oxytocin in humans has favorable effects on social anxiety symptomology. Other disorders, including autism, schizophrenia, and anorexia, have components of social anxiety in their pathophysiology. The therapeutic role of oxytocin for social dysfunction in these disorders is discussed. PMID:28867943

Oxytocin and social functioning.

PubMed

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

2017-06-01

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 potential therapeutic option for individuals with social anxiety. Animal research both in nonprimates and primates supports oxytocin's role in facilitation of prosocial behaviors and its anxiolytic effects. Human studies indicate significant associations between social anxiety and oxytocin receptor gene alleles, as well as social anxiety and oxytocin plasma levels. In addition, intranasal administration of oxytocin in humans has favorable effects on social anxiety symptomology. Other disorders, including autism, schizophrenia, and anorexia, have components of social anxiety in their pathophysiology. The therapeutic role of oxytocin for social dysfunction in these disorders is discussed.

The function of oxytocin: a potential biomarker for prostate cancer diagnosis and promoter of prostate cancer.

PubMed

Xu, Huan; Fu, Shi; Chen, Qi; Gu, Meng; Zhou, Juan; Liu, Chong; Chen, Yanbo; Wang, Zhong

2017-05-09

To measure the level of oxytocin in serum and prostate cancer (PCa) tissue and study its effect on the proliferation of PCa cells. Oxytocin level in serum was significantly increased in PCa patients compared with the no-carcinoma individuals. Additionally, the levels of oxytocin and its receptor were also elevated in the PCa tissue. However, no significant difference existed among the PCa of various Gleason grades. Western blot analysis confirmed the previous results and revealed an increased expression level of APPL1. The level of oxytocin in serum was measured by ELISA analysis. The expression of oxytocin and its receptor in prostate was analyzed by immunohistochemistry. The proliferation and apoptosis of PCa cells were assessed by the Cell Counting Kit 8 (CCK8) assay, cell cycle analysis and caspase3 activity analysis, respectively. Western blot analysis was used for the detection of PCNA, Caspase3 and APPL1 protein levels. Serum and prostatic oxytocin levels are increased in the PCa subjects. Serum oxytocin level may be a biomarker for PCa in the future. Oxytocin increases PCa growth and APPL1 expression.

Can Oxytocin Enhance the Placebo Effect?

ClinicalTrials.gov

2018-02-06

Oxytocin Effect on Memory Performance During Phase 1; Oxytocin Effect on Memory Performance During Phase 2; Oxytocin Effect on Memory Performance During Phase 3; Oxytocin Effect on Memory Performance During Phase 4

Oxytocin and Migraine Headache.

PubMed

Tzabazis, Alexander; Kori, Shashi; Mechanic, Jordan; Miller, James; Pascual, Conrado; Manering, Neil; Carson, Dean; Klukinov, Michael; Spierings, Egilius; Jacobs, Daniel; Cuellar, Jason; Frey, William H; Hanson, Leah; Angst, Martin; Yeomans, David C

2017-05-01

This article reviews material presented at the 2016 Scottsdale Headache Symposium. This presentation provided scientific results and rationale for the use of intranasal oxytocin for the treatment of migraine headache. Results from preclinical experiments are reviewed, including in vitro experiments demonstrating that trigeminal ganglia neurons possess oxytocin receptors and are inhibited by oxytocin. Furthermore, most of these same neurons contain CGRP, the release of which is inhibited by oxytocin. Results are also presented which demonstrate that nasal oxytocin inhibits responses of trigeminal nucleus caudalis neurons to noxious stimulation using either noxious facial shock or nitroglycerin infusion. These studies led to testing the analgesic effect of intranasal oxytocin in episodic migraineurs-studies which did not meet their primary endpoint of pain relief at 2 h, but which were highly informative and led to additional rat studies wherein inflammation was found to dramatically upregulate the number of oxytocin receptors available on trigeminal neurons. This importance of inflammation was supported by a series of in vivo rat behavioral studies, which demonstrated a clear craniofacial analgesic effect when a pre-existing inflammatory injury was present. The significance of inflammation was further solidified by a small single-dose clinical study, which showed analgesic efficacy that was substantially stronger in chronic migraine patients that had not taken an anti-inflammatory drug within 24 h of oxytocin dosing. A follow-on open label study examining effects of one month of intranasal oxytocin dosing did show a reduction in pain, but a more impressive decrease in the frequency of headaches in both chronic and high frequency episodic migraineurs. This study led to a multicountry double blind, placebo controlled study studying whether, over 2 months of dosing, "as needed" dosing of intranasal oxytocin by chronic and high frequency migraineurs would reduce the

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

PubMed

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

Oxytocin stimulates hippocampal neurogenesis via oxytocin receptor expressed in CA3 pyramidal neurons.

PubMed

Lin, Yu-Ting; Chen, Chien-Chung; Huang, Chiung-Chun; Nishimori, Katsuhiko; Hsu, Kuei-Sen

2017-09-14

In addition to the regulation of social and emotional behaviors, the hypothalamic neuropeptide oxytocin has been shown to stimulate neurogenesis in adult dentate gyrus; however, the mechanisms underlying the action of oxytocin are still unclear. Taking advantage of the conditional knockout mouse model, we show here that endogenous oxytocin signaling functions in a non-cell autonomous manner to regulate survival and maturation of newly generated dentate granule cells in adult mouse hippocampus via oxytocin receptors expressed in CA3 pyramidal neurons. Through bidirectional chemogenetic manipulations, we also uncover a significant role for CA3 pyramidal neuron activity in regulating adult neurogenesis in the dentate gyrus. Retrograde neuronal tracing combined with immunocytochemistry revealed that the oxytocin neurons in the paraventricular nucleus project directly to the CA3 region of the hippocampus. Our findings reveal a critical role for oxytocin signaling in adult neurogenesis.Oxytocin (OXT) has been implicated in adult neurogenesis. Here the authors show that CA3 pyramidal cells in the adult mouse hippocampus express OXT receptors and receive inputs from hypothalamic OXT neurons; activation of OXT signaling in CA3 pyramidal cells promotes the survival and maturation of newborn neurons in the dentate gyrus in a non-cell autonomous manner.

Oxytocin Augmentation in Spontaneously Laboring, Nulliparous Women: Multilevel Assessment of Maternal BMI and Oxytocin Dose

PubMed Central

Carlson, Nicole S.; Corwin, Elizabeth J.; Lowe, Nancy K.

2017-01-01

Background Synthetic oxytocin, the primary tool for labor augmentation, is less effective among obese women, leading to more unplanned cesarean deliveries for slow labor progress. It is not known if obese women require higher doses of oxytocin due to maternal, fetal, or labor factors related to maternal obesity. Objectives This study had two main objectives: 1) Examine the influence of maternal body mass index (BMI) on hourly doses of oxytocin from augmentation initiation until vaginal delivery in obese women; and 2) Examine the influence of other maternal, fetal, and labor factors on hourly doses of oxytocin in obese women. Study design Longitudinal study of a cohort (N = 136) of healthy, nulliparous, spontaneously laboring obese women (BMI ≥ 30 kg/m2) who received oxytocin augmentation and achieved vaginal delivery. We performed iterative multilevel analyses to examine the influence of maternal BMI and other factors on hourly oxytocin doses. Results Maternal BMI explained 16.56% (95% CI [13.7-20.04], p < 0.001) of the variance in hourly oxytocin doses received in a multilevel model controlling for influence of maternal, fetal, and labor characteristics. Maternal age, gestational age, status of amniotic membranes at hospital admission, and admission cervical dilation examination were not significant; however, neonatal birthweight and cervical dilation at oxytocin initiation were significant predictors of hourly oxytocin dose in these women (p < 0.001). Conclusions Even when parturition preparation has progressed adequately for spontaneous labor initiation, there still may be some obesity-related blunting of myometrial contractility and response to oxytocin used for augmentation. PMID:28347147

Oxytocin Augmentation in Spontaneously Laboring, Nulliparous Women: Multilevel Assessment of Maternal BMI and Oxytocin Dose.

PubMed

Carlson, Nicole S; Corwin, Elizabeth J; Lowe, Nancy K

2017-07-01

Synthetic oxytocin, the primary tool for labor augmentation, is less effective among obese women, leading to more unplanned cesarean deliveries for slow labor progress. It is not known if obese women require higher doses of oxytocin due to maternal, fetal, or labor factors related to maternal obesity. This study had two main objectives: (1) examine the influence of maternal body mass index (BMI) on hourly doses of oxytocin from augmentation initiation until vaginal delivery in obese women; and (2) examine the influence of other maternal, fetal, and labor factors on hourly doses of oxytocin in obese women. Longitudinal study of a cohort ( N = 136) of healthy, nulliparous, spontaneously laboring obese women (BMI ≥ 30 kg/m 2 ) who received oxytocin augmentation and achieved vaginal delivery. We performed iterative multilevel analyses to examine the influence of maternal BMI and other factors on hourly oxytocin doses. Maternal BMI explained 16.56% (95% confidence interval [CI] = [13.7, 20.04], p < .001) of the variance in hourly oxytocin doses received in a multilevel model controlling for influence of maternal, fetal, and labor characteristics. Maternal age, gestational age, status of amniotic membranes at hospital admission, and admission cervical dilation examination were not significant; however, neonatal birthweight and cervical dilation at oxytocin initiation were significant predictors of hourly oxytocin dose in these women ( p < .001). Even when parturition preparation has progressed adequately for spontaneous labor initiation, there still may be some obesity-related blunting of myometrial contractility and response to oxytocin used for augmentation.

21 CFR 522.1680 - Oxytocin injection.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Oxytocin injection. 522.1680 Section 522.1680 Food... Oxytocin injection. (a) Specifications. Each milliliter (mL) of solution contains 20 USP units oxytocin. (b... 10 to 20. Sows 0.25 to 1.0 5 to 20. (2) Indications for use. Oxytocin may be used as a uterine...

Oxytocin and Social Bonds: The Role of Oxytocin in Perceptions of Romantic Partners' Bonding Behavior.

PubMed

Algoe, Sara B; Kurtz, Laura E; Grewen, Karen

2017-12-01

In this research, we tested hypotheses about the role of oxytocin in adult human bonding. Inspired by revisiting the research on pair bonding in microtine voles that fueled psychologists' interest in the role of oxytocin in social life, we drew on recent theory from affective and relationship science to identify a well-defined bonding context for human romantic relationships. We then paired these behaviors and subjective psychological responses with a measure of naturally circulating oxytocin. In 129 romantically involved adults whose partner expressed gratitude to them in the lab, greater oxytocin over the prior 24 hr was associated with greater perceptions of the expresser's responsiveness and gratitude, as well as greater experienced love, but not general affective reward. Moreover, in this one-time conversation, higher oxytocin acted like rose-colored glasses, attenuating the effect of a partner's behaviorally coded expressive behavior on perceptions of the expresser's responsiveness. These results justify future research on the role of oxytocin in psychological aspects of growth processes.

[Association between oxytocin augmentation intervals and the risk of postpartum haemorrhage].

PubMed

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 intervals<20minutes and≥20minutes. Obstetrical and neonatal issues were analyzed according to the duration oxytocin 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 were<20minutes (12.1% vs 4.3%; P=0.002). Our study demonstrated an increased risk of PPH for primiparous women in spontaneous labour who received oxytocin with augmentation intervals shorter than 20minutes. Copyright © 2016. Published by Elsevier Masson SAS.

Pharmacologic characterization of the oxytocin receptor in human uterine smooth muscle cells

PubMed Central

Tahara, Atsuo; Tsukada, Junko; Tomura, Yuichi; Wada, Koh-ichi; Kusayama, Toshiyuki; Ishii, Noe; Yatsu, Takeyuki; Uchida, Wataru; Tanaka, Akihiro

2000-01-01

[3H]-oxytocin was used to characterize the oxytocin receptor found in human uterine smooth muscle cells (USMC). Specific binding of [3H]-oxytocin to USMC plasma membranes was dependent upon time, temperature and membrane protein concentration. Scatchard plot analysis of equilibrium binding data revealed the existence of a single class of high-affinity binding sites with an apparent equilibrium dissociation constant (Kd) of 0.76 nM and a maximum receptor density (Bmax) of 153 fmol mg−1 protein. The Hill coefficient (nH) did not differ significantly from unity, suggesting binding to homogenous, non-interacting receptor populations. Competitive inhibition of [3H]-oxytocin binding showed that oxytocin and vasopressin (AVP) receptor agonists and antagonists displaced [3H]-oxytocin in a concentration-dependent manner. The order of potencies for peptide agonists and antagonists was: oxytocin>[Asu1,6]-oxytocin>AVP= atosiban>d(CH2)5Tyr(Me)AVP>[Thr4,Gly7]-oxytocin>dDAVP, and for nonpeptide antagonists was: L-371257>YM087>SR 49059>OPC-21268>SR 121463A>OPC-31260. Oxytocin significantly induced concentration-dependent increase in intracellular Ca2+ concentration ([Ca2+]i) and hyperplasia in USMC. The oxytocin receptor antagonists, atosiban and L-371257, potently and concentration-dependently inhibited oxytocin-induced [Ca2+]i increase and hyperplasia. In contrast, the V1A receptor selective antagonist, SR 49059, and the V2 receptor selective antagonist, SR 121463A, did not potently inhibit oxytocin-induced [Ca2+]i increase and hyperplasia. The potency order of antagonists in inhibiting oxytocin-induced [Ca2+]i increase and hyperplasia was similar to that observed in radioligand binding assays. In conclusion, these data provide evidence that the high-affinity [3H]-oxytocin binding site found in human USMC is a functional oxytocin receptor coupled to [Ca2+]i increase and cell growth. Thus human USMC may prove to be a valuable tool in further investigation of the

Pharmacologic characterization of the oxytocin receptor in human uterine smooth muscle cells.

PubMed

Tahara, A; Tsukada, J; Tomura, Y; Wada, K i; Kusayama, T; Ishii, N; Yatsu, T; Uchida, W; Tanaka, A

2000-01-01

[(3)H]-oxytocin was used to characterize the oxytocin receptor found in human uterine smooth muscle cells (USMC). Specific binding of [(3)H]-oxytocin to USMC plasma membranes was dependent upon time, temperature and membrane protein concentration. Scatchard plot analysis of equilibrium binding data revealed the existence of a single class of high-affinity binding sites with an apparent equilibrium dissociation constant (K(d)) of 0.76 nM and a maximum receptor density (B(max)) of 153 fmol mg(-1) protein. The Hill coefficient (n(H)) did not differ significantly from unity, suggesting binding to homogenous, non-interacting receptor populations. Competitive inhibition of [(3)H]-oxytocin binding showed that oxytocin and vasopressin (AVP) receptor agonists and antagonists displaced [(3)H]-oxytocin in a concentration-dependent manner. The order of potencies for peptide agonists and antagonists was: oxytocin>[Asu(1,6)]-oxytocin>AVP= atosiban>d(CH(2))(5)Tyr(Me)AVP>[Thr(4),Gly(7)]-oxytocin>dDAVP, and for nonpeptide antagonists was: L-371257>YM087>SR 49059>OPC-21268>SR 121463A>OPC-31260. Oxytocin significantly induced concentration-dependent increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) and hyperplasia in USMC. The oxytocin receptor antagonists, atosiban and L-371257, potently and concentration-dependently inhibited oxytocin-induced [Ca(2+)](i) increase and hyperplasia. In contrast, the V(1A) receptor selective antagonist, SR 49059, and the V(2) receptor selective antagonist, SR 121463A, did not potently inhibit oxytocin-induced [Ca(2+)](i) increase and hyperplasia. The potency order of antagonists in inhibiting oxytocin-induced [Ca(2+)](i) increase and hyperplasia was similar to that observed in radioligand binding assays. In conclusion, these data provide evidence that the high-affinity [(3)H]-oxytocin binding site found in human USMC is a functional oxytocin receptor coupled to [Ca(2+)](i) increase and cell growth. Thus human USMC may prove to be a valuable

Oxytocin promotes altruistic punishment.

PubMed

Aydogan, Gökhan; Furtner, Nadja C; Kern, Bianca; Jobst, Andrea; Müller, Norbert; Kocher, Martin G

2017-11-01

The role of neuromodulators in the enforcement of cooperation is still not well understood. Here, we provide evidence that intranasal applied oxytocin, an important hormone for modulating social behavior, enhances the inclination to sanction free-riders in a social dilemma situation. Contrary to the notion of oxytocin being a pro-social hormone, we found that participants treated with oxytocin exhibited an amplification of self-reported negative social emotions such as anger towards free-riders, ultimately resulting in higher magnitude and frequency of punishment of free-riders compared to placebo. Furthermore, we found initial evidence that oxytocin contributes to the positive effects of a punishment institution by rendering cooperation preferable in the oxytocin condition for even the most selfish players when punishment was available. Together, these findings imply that the neural circuits underlying altruistic punishment are partly targeted by the oxytonergic system and highlight the importance of neuromodulators in group cohesion and norm enforcement within social groups. © The Author (2017). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

21 CFR 522.1680 - Oxytocin.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Oxytocin. 522.1680 Section 522.1680 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1680 Oxytocin. (a) Specifications. Each milliliter (mL) of solution contains 20 USP units oxytocin. (b) Sponsors. See Nos. , 000859...

Intranasal Oxytocin: Myths and Delusions.

PubMed

Leng, Gareth; Ludwig, Mike

2016-02-01

Despite widespread reports that intranasal application of oxytocin has a variety of behavioral effects, very little of the huge amounts applied intranasally appears to reach the cerebrospinal fluid. However, peripheral concentrations are increased to supraphysiologic levels, with likely effects on diverse targets including the gastrointestinal tract, heart, and reproductive tract. The wish to believe in the effectiveness of intranasal oxytocin appears to be widespread and needs to be guarded against with scepticism and rigor. Preregistering trials, declaring primary and secondary outcomes in advance, specifying the statistical methods to be applied, and making all data openly available should minimize problems of publication bias and questionable post hoc analyses. Effects of intranasal oxytocin also need proper dose-response studies, and such studies need to include control subjects for peripheral effects, by administering oxytocin peripherally and by blocking peripheral actions with antagonists. Reports in the literature of oxytocin measurements include many that have been made with discredited methodology. Claims that peripheral measurements of oxytocin reflect central release are questionable at best. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Oxytocin promotes human ethnocentrism

PubMed Central

De Dreu, Carsten K. W.; Greer, Lindred L.; Van Kleef, Gerben A.; Shalvi, Shaul; Handgraaf, Michel J. J.

2011-01-01

Human ethnocentrism—the tendency to view one's group as centrally important and superior to other groups—creates intergroup bias that fuels prejudice, xenophobia, and intergroup violence. Grounded in the idea that ethnocentrism also facilitates within-group trust, cooperation, and coordination, we conjecture that ethnocentrism may be modulated by brain oxytocin, a peptide shown to promote cooperation among in-group members. In double-blind, placebo-controlled designs, males self-administered oxytocin or placebo and privately performed computer-guided tasks to gauge different manifestations of ethnocentric in-group favoritism as well as out-group derogation. Experiments 1 and 2 used the Implicit Association Test to assess in-group favoritism and out-group derogation. Experiment 3 used the infrahumanization task to assess the extent to which humans ascribe secondary, uniquely human emotions to their in-group and to an out-group. Experiments 4 and 5 confronted participants with the option to save the life of a larger collective by sacrificing one individual, nominated as in-group or as out-group. Results show that oxytocin creates intergroup bias because oxytocin motivates in-group favoritism and, to a lesser extent, out-group derogation. These findings call into question the view of oxytocin as an indiscriminate “love drug” or “cuddle chemical” and suggest that oxytocin has a role in the emergence of intergroup conflict and violence. PMID:21220339

Urinary oxytocin in capuchin monkeys: Validation and the influence of social behavior.

PubMed

Benítez, Marcela E; Sosnowski, Meghan J; Tomeo, Olivia B; Brosnan, Sarah F

2018-05-24

In highly social species, like primates, oxytocin plays an important role in cooperation, and in the formation and maintenance of social relationships. Despite recent interest in the relationship between oxytocin and social behavior in nonhuman primates, relatively little is known about endogenous oxytocin in social New World Monkeys. In this paper, we investigate the relationship between oxytocin and affiliative behaviors in socially-housed captive capuchin monkeys (Sapajus [Cebus] apella) by first validating methods of analysis of urinary oxytocin in this species and, second, examining the effects of grooming and fur-rubbing behavior on oxytocin concentrations and further affiliative behavior. In the validation, we found that intranasal exogenous oxytocin significantly increased urinary oxytocin 15-60 min post-administration. Oxytocin was also implicated in both grooming and fur-rubbing behaviors. We found that oxytocin concentrations increased after subjects engaged in grooming or fur-rubbing. In addition, we found that fur-rubbing influenced affiliative behaviors, both during and after a social fur-rubbing bout. While individuals spent more time in contact and proximity while fur-rubbing, immediately following the fur-rubbing event (15-30 min afterwards) all affiliative behaviors decreased. This supports previous research that oxytocin may, in fact, initially be related to increased social distance in this species. Yet, an increase in all affiliative behaviors 30-45 min after the onset of fur-rubbing suggests that fur-rubbing, like grooming, may ultimately function to strengthen social relationships. Overall, these results support a critical role for oxytocin in affiliative behaviors that maintain and strengthen social relationships in capuchin monkeys, and highlight the complexity of the interactions among oxytocin, affiliative behaviors, and social bonding. © 2018 Wiley Periodicals, Inc.

Oxytocin and Social Bonds: The Role of Oxytocin in Perceptions of Romantic Partners’ Bonding Behavior

PubMed Central

Algoe, Sara B.; Kurtz, Laura E.; Grewen, Karen

2017-01-01

In this research, we tested hypotheses about the role of oxytocin in adult human bonding. Inspired by revisiting the research on pair bonding in microtine voles that fueled psychologists’ interest in the role of oxytocin in social life, we drew on recent theory from affective and relationship science to identify a well-defined bonding context for human romantic relationships. We then paired these behaviors and subjective psychological responses with a measure of naturally circulating oxytocin. In 129 romantically involved adults whose partner expressed gratitude to them in the lab, greater oxytocin over the prior 24 hr was associated with greater perceptions of the expresser’s responsiveness and gratitude, as well as greater experienced love, but not general affective reward. Moreover, in this one-time conversation, higher oxytocin acted like rose-colored glasses, attenuating the effect of a partner’s behaviorally coded expressive behavior on perceptions of the expresser’s responsiveness. These results justify future research on the role of oxytocin in psychological aspects of growth processes. PMID:28968183

Oxytocin and potential benefits for obesity treatment.

PubMed

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.

Meta-analysis of the effects of intranasal oxytocin on interpretation and expression of emotions.

PubMed

Leppanen, Jenni; Ng, Kah Wee; Tchanturia, Kate; Treasure, Janet

2017-07-01

Accurate interpretation and appropriate expression of emotions are key aspects of social-cognition. Several mental disorders are characterised by transdiagnostic difficulties in these areas and, recently, there has been increasing interest in exploring the effects of oxytocin on social-emotional functioning. This review consists of 33 studies. Fifteen of the studies included people with autism spectrum disorder, schizophrenia, borderline personality disorder, frontotemporal dementia, anorexia nervosa, bulimia nervosa, post-traumatic stress disorder, depression, and opioid and alcohol dependence. We conducted ten meta-analyses examining the effects of intranasal oxytocin on expression of emotions, emotional theory of mind, sensitivity to recognise basic emotions, and recognition of basic emotions. A single dose of intranasal oxytocin significantly improved the recognition of basic emotions, particularly fear, and increased the expression of positive emotions among the healthy individuals. Oxytocin did not significantly influence theory of mind or the expression of negative emotions among the healthy individuals. Finally, intranasal oxytocin did not significantly influence interpretation or expression of emotions among the clinical populations. Copyright © 2017. Published by Elsevier Ltd.

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

PubMed

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.

Annexin A1 Complex Mediates Oxytocin Vesicle Transport

PubMed Central

Makani, Vishruti; Sultana, Rukhsana; Sie, Khin Sander; Orjiako, Doris; Tatangelo, Marco; Dowling, Abigail; Cai, Jian; Pierce, William; Butterfield, D. Allan; Hill, Jennifer; Park, Joshua

2013-01-01

Oxytocin is a major neuropeptide that modulates the brain functions involved in social behavior and interaction. Despite of the importance of oxytocin for neural control of social behavior, little is known about the molecular mechanism(s) by which oxytocin secretion in the brain is regulated. Pro-oxytocin is synthesized in the cell bodies of hypothalamic neurons in the supraoptic and paraventricular nuclei and processed to a 9-amino-acid mature form during post-Golgi transport to the secretion sites at the axon terminals and somatodendritic regions. Oxytocin secreted from the somatodendritic regions diffuses throughout the hypothalamus and its neighboring brain regions. Some oxytocin-positive axons innervate and secrete oxytocin to the brain regions distal to the hypothalamus. Brain oxytocin binds to its receptors in the brain regions involved in social behavior. Oxytocin is also secreted from the axon terminal at the posterior pituitary gland into the blood circulation. We have discovered a new molecular complex consisting of annexin A1 (ANXA1), A-kinase anchor protein 150 (AKAP150), and microtubule motor, that controls the distribution of oxytocin vesicles between the axon and the cell body in a protein kinase A (PKA)- and protein kinase C (PKC)-sensitive manner. ANXA1 showed significant co-localization with oxytocin vesicles. Activation of PKA enhanced the association of kinesin-2 with ANXA1, thus increasing the axon-localization of oxytocin vesicles. Conversely, activation of PKC decreased the binding of kinesin-2 to ANXA1, thus attenuating the axon-localization of oxytocin vesicles. Our study suggests that ANXA1 complex coordinates the actions of PKA and PKC to control the distribution of oxytocin vesicles between the axon and the cell body. PMID:24118254

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olszewski, Pawel K., E-mail: olsze005@umn.edu; Minnesota Obesity Center, Saint Paul, MN 55108; Fredriksson, Robert

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 throughmore » 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.« less

Oxytocin in the Treatment of Dystocia in Mice

PubMed Central

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

Heat-Stable Dry Powder Oxytocin Formulations for Delivery by Oral Inhalation.

PubMed

Fabio, Karine; Curley, Kieran; Guarneri, Joseph; Adamo, Benoit; Laurenzi, Brendan; Grant, Marshall; Offord, Robin; Kraft, Kelly; Leone-Bay, Andrea

2015-12-01

In this work, heat stable dry powders of oxytocin (OT) suitable for delivery by oral inhalation were prepared. The OT dry powders were prepared by spray drying using excipients chosen to promote OT stability including trehalose, isoleucine, polyvinylpyrrolidone, citrate (sodium citrate and citric acid), and zinc salts (zinc chloride and zinc citrate). Characterization by laser diffraction indicated that the OT dry powders had a median particle size of 2 μm, making them suitable for delivery by inhalation. Aerodynamic performance upon discharge from proprietary dry powder inhalers was evaluated by Andersen cascade impaction (ACI) and in an anatomically correct airway (ACA) model, and confirmed that the powders had excellent aerodynamic performance, with respirable fractions up to 77% (ACI, 30 L/min). Physicochemical characterization demonstrated that the powders were amorphous (X-ray diffraction) with high glass transition temperature (modulated differential scanning calorimetry, MDSC), suggesting the potential for stabilization of the OT in a glassy amorphous matrix. OT assay and impurity profile were conducted by reverse phase HPLC and liquid chromatography-mass spectrometry (LC-MS) after storage up to 32 weeks at 40°C/75%RH. Analysis demonstrated that OT dry powders containing a mixture of citrate and zinc salts retained more than 90% of initial assay after 32 weeks storage and showed significant reduction in dimers and trisulfide formation (up to threefold reduction compared to control).

The association between the oxytocin receptor gene (OXTR) and hypnotizability.

PubMed

Bryant, Richard A; Hung, Lynette; Dobson-Stone, Carol; Schofield, Peter R

2013-10-01

Hypnosis has puzzled scientists for centuries, and particularly the reason why some people are prone to engaging in suggested experiences discordant with external reality. Absorption in internal experience is one key component of the hypnotic response. The neuropeptide oxytocin has been posited to heighten sensitivity to external cues, and it is possible that individual differences in oxytocin-related capacity to engage in external or internal experiences influences hypnotic response. To test this proposal, 185 Caucasian individuals provided saliva samples for analysis of polymorphisms in the oxytocin receptor gene, COMT, and independently completed standardized measures of hypnotizability and absorption. Participants with the GG genotype at rs53576 were characterized by lower hypnotizability and absorption scores than those with the A allele; there was no association between hyponotizability and COMT. These findings provide initial evidence that the capacity to respond to suggestions for altered internal experience is influenced by the oxytocin receptor gene, and is consistent with evidence that oxytocin plays an important role in modulating the extent to which people engage with external versus internal experiences. Copyright © 2013 Elsevier Ltd. All rights reserved.

A prospective randomized trial comparing Foley catheter, oxytocin, and combination Foley catheter-oxytocin for labour induction with unfavourable cervix.

PubMed

El Khouly, Nabih I

2017-04-01

The purpose of this study was to evaluate the effectiveness and safety of transcervical Foley catheter with and without oxytocin versus oxytocin alone for labour induction with unfavourable cervix. This trial enrolled 108 women with singleton pregnancies presented for labour induction with unfavourable cervix. Patients were randomly assigned to receive Foley catheter alone (I), Foley catheter plus oxytocin (II) or oxytocin alone (III). Outcomes were analysed in terms of success of induction, induction delivery interval, route of delivery, dose and duration of oxytocin, and complications. Successful normal vaginal delivery was more common in group I (p = .02) compared to group III. Induction delivery time was statistically shorter in group II and group III (p < .001). Patients in group I required significantly less oxytocin dose and duration (p < .001). This led to our conclusion that induction of labour with Foley catheter without oxytocin increases success rate of normal vaginal delivery; however, it has a longer induction delivery interval with similar complications.

Oxytocin Reduces Ethanol Self-Administration in Mice

PubMed Central

King, Courtney E.; Griffin, William C.; Luderman, Lauryn N.; Kates, Malcolm M.; McGinty, Jacqueline F.; Becker, Howard C.

2017-01-01

Background Excessive ethanol consumption remains an important health concern and effective treatments are lacking. The central oxytocin system has emerged as a potentially important therapeutic target for alcohol and drug addiction. These studies tested the hypothesis that oxytocin reduces ethanol consumption. Methods Male C57BL/6J mice were given access to ethanol (20% v/v) using a model of binge-like drinking (“drinking-in-the-dark”) that also included the use of lickometer circuits to evaluate the temporal pattern of intake as well as 2-bottle choice drinking in the home cage. In addition, ethanol (12% v/v) and sucrose (5% w/v) self-administration on fixed- and progressive- ratio schedules were also evaluated. A wide range of systemically administered oxytocin doses were tested (0 to 10 mg/kg) in these models. Results Oxytocin (0, 0.3, 1, 3 or 10mg/kg) dose-dependently reduced ethanol consumption (maximal 45% reducton) in the binge drinking model, with lower effective doses having minimal effects on general locomotor activity. Oxytocin’s effect was blocked by pretreatment with an oxytocin receptor antagonist and the pattern of contacts (licks) at the ethanol bottle suggested a reduction in motivation to drink ethanol. Oxytocin decreased 2-bottle choice drinking without altering general fluid intake. Oxytocin also reduced operant responding for ethanol and sucrose in a dose-related manner. However, oxytocin decreased responding and motivation (breakpoint values) for ethanol at doses that did not alter responding for sucrose. Discussion These results indicate that oxytocin reduces ethanol consumption in different models of self-administration. The effects are not likely due to a general sedative effect of the neuropeptide. Further, oxytocin reduces motivation for ethanol at doses that do not alter responding for a natural reward (sucrose). While some evidence supports a role for oxytocin receptors in mediating these effects, additional studies are needed to

Oxytocin Enables Maternal Behavior by Balancing Cortical Inhibition

PubMed Central

Marlin, Bianca J.; Mitre, Mariela; D’amour, James A.; Chao, Moses V.; Froemke, Robert C.

2015-01-01

Oxytocin is important for social interactions and maternal behavior. However, little is known about when, where, and how oxytocin modulates neural circuits to improve social cognition. Here we show how oxytocin enables pup retrieval behavior in female mice by enhancing auditory cortical pup call responses. Retrieval behavior required left but not right auditory cortex, was accelerated by oxytocin in left auditory cortex, and oxytocin receptors were preferentially expressed in left auditory cortex. Neural responses to pup calls were lateralized, with co-tuned and temporally-precise excitatory and inhibitory responses in left cortex of maternal but not pup-naive adults. Finally, pairing calls with oxytocin enhanced responses by balancing the magnitude and timing of inhibition with excitation. Our results describe fundamental synaptic mechanisms by which oxytocin increases the salience of acoustic social stimuli. Furthermore, oxytocin-induced plasticity provides a biological basis for lateralization of auditory cortical processing. PMID:25874674

Oxytocin Reduces Ethanol Self-Administration in Mice.

PubMed

King, Courtney E; Griffin, William C; Luderman, Lauryn N; Kates, Malcolm M; McGinty, Jacqueline F; Becker, Howard C

2017-05-01

Excessive ethanol (EtOH) consumption remains an important health concern and effective treatments are lacking. The central oxytocin system has emerged as a potentially important therapeutic target for alcohol and drug addiction. These studies tested the hypothesis that oxytocin reduces EtOH consumption. Male C57BL/6J mice were given access to EtOH (20% v/v) using a model of binge-like drinking ("drinking in the dark") that also included the use of lickometer circuits to evaluate the temporal pattern of intake as well as 2-bottle choice drinking in the home cage. In addition, EtOH (12% v/v) and sucrose (5% w/v) self-administration on fixed- and progressive-ratio schedules were also evaluated. A wide range of systemically administered oxytocin doses were tested (0 to 10 mg/kg) in these models. Oxytocin (0, 0.3, 1, 3, or 10 mg/kg) dose dependently reduced EtOH consumption (maximal 45% reduction) in the binge drinking model, with lower effective doses having minimal effects on general locomotor activity. Oxytocin's effect was blocked by pretreatment with an oxytocin receptor antagonist, and the pattern of contacts (licks) at the EtOH bottle suggested a reduction in motivation to drink EtOH. Oxytocin decreased 2-bottle choice drinking without altering general fluid intake. Oxytocin also reduced operant responding for EtOH and sucrose in a dose-related manner. However, oxytocin decreased responding and motivation (breakpoint values) for EtOH at doses that did not alter responding for sucrose. These results indicate that oxytocin reduces EtOH consumption in different models of self-administration. The effects are not likely due to a general sedative effect of the neuropeptide. Further, oxytocin reduces motivation for EtOH at doses that do not alter responding for a natural reward (sucrose). While some evidence supports a role for oxytocin receptors in mediating these effects, additional studies are needed to further elucidate underlying mechanisms. Nevertheless, these

The Concentrations of Circulating Plasma Oxytocin and the Pattern of Oxytocin Release in Mare during Oestrus and after Ovulation

NASA Astrophysics Data System (ADS)

Bae, Sung Eun

Mares susceptible to persistent mating-induced endometritis (PMIE) accumulate intrauterine fluid after mating. One of the factors causing delayed uterine clearance is thought to be impaired uterine contractility. Oxytocin is central in controlling myometrial contractility. The objective of the present study was to describe peripheral oxytocin release during estrus and in the early postovulatory period in reproductively-normal mares and to compare the baseline circulating oxytocin concentrations in reproductively-normal mares and mares with PMIE. Blood samples were collected from reproductively-normal mares (n=5) from day -5 of estrus to day 2 postovulation and every 5 min for 30 min from reproductively-normal mares (n=5) and mares with PMIE (n=5) on day 3 of estrus. Pulsatile secretion of oxytocin was observed in all mares. Mean plasma oxytocin concentrations were significantly higher (P<0.05) in estrus (day -5 to day -2) than on the day of ovulation (day 0). After ovulation, plasma oxytocin concentrations tended to increase. On day 3 of estrus, plasma oxytocin concentrations were significantly higher (P<0.01) in reproductively-normal mares than in mares with PMIE. The results showed there is a significant difference in plasma oxytocin concentrations between mares to PMIE. The low plasma oxytocin concentrations in mares with PMIE may contribute to predisposing factors in their poor uterine clearance in these mares.

Genetic modulation of oxytocin sensitivity: a pharmacogenetic approach.

PubMed

Chen, F S; Kumsta, R; Dvorak, F; Domes, G; Yim, O S; Ebstein, R P; Heinrichs, M

2015-10-27

Intranasal administration of the neuropeptide oxytocin has been shown to influence a range of complex social cognitions and social behaviors, and it holds therapeutic potential for the treatment of mental disorders characterized by social functioning deficits such as autism, social phobia and borderline personality disorder. However, considerable variability exists in individual responses to oxytocin administration. Here, we undertook a study to investigate the role of genetic variation in sensitivity to exogenous oxytocin using a socioemotional task. In a randomized, double-blind, placebo-controlled experiment with a repeated-measures (crossover) design, we assessed the performance of 203 men on an emotion recognition task under oxytocin and placebo. We took a haplotype-based approach to investigate the association between oxytocin receptor gene variation and oxytocin sensitivity. We identified a six-marker haplotype block spanning the promoter region and intron 3 that was significantly associated with our measure of oxytocin sensitivity. Specifically, the TTCGGG haplotype comprising single-nucleotide polymorphisms rs237917-rs2268498-rs4564970-rs237897-rs2268495-rs53576 is associated with increased emotion recognition performance under oxytocin versus placebo, and the CCGAGA haplotype with the opposite pattern. These results on the genetic modulation of sensitivity to oxytocin document a significant source of individual differences with implications for personalized treatment approaches using oxytocin administration.

Benefits of oxytocin administration in obstructive sleep apnea.

PubMed

Jain, Vivek; Marbach, Joseph; Kimbro, Shawn; Andrade, David C; Jain, Arad; Capozzi, Eleanor; Mele, Kyle; Del Rio, Rodrigo; Kay, Matthew W; Mendelowitz, David

2017-11-01

Activation of oxytocin receptors has shown benefits in animal models of obstructive sleep apnea (OSA). We tested if nocturnal oxytocin administration could have beneficial effects in OSA patients. Eight patients diagnosed with OSA were administered intranasal oxytocin (40 IU). Changes in cardiorespiratory events during sleep, including apnea and hypopnea durations and frequency, risk of event-associated arousals, and heart rate variability, were assessed. Oxytocin significantly increased indexes of parasympathetic activity, including heart rate variability, total sleep time, and the postpolysommogram sleep assessment score, an index of self-reported sleep satisfaction. Although the apnea-hypopnea index was not significantly changed with oxytocin administration, when apnea and hypopnea events were compared independently, the frequency of hypopneas, but not apneas, was significantly ( P ≤ 0.005) decreased with oxytocin treatment. Both apneas and hypopneas were significantly shortened in duration with oxytocin treatment. Oxytocin treatment significantly decreased the percent of apnea and hypopnea events that were accompanied with an arousal. Oxytocin administration has the potential to restore cardiorespiratory homeostasis and reduce some clinically important (objective and patient-reported) adverse events that occur with OSA. Additional studies are needed to further understand the mechanisms by which oxytocin promotes these changes in cardiorespiratory and autonomic function in OSA patients. Copyright © 2017 the American Physiological Society.

Man and the chimaera. Selective versus neutral oxytocin evolution.

PubMed

Acher, R; Chauvet, J; Chauvet, M T

1995-01-01

The oxytocin/vasopressin superfamily encompasses vertebrate and invertebrate peptides and therefore the ancestral gene encoding the precursor protein antedates the divergence between the two groups, about 700 million years ago. The preserved nonapeptide pattern indicates that both the precursor structures and the processing enzymatic machinery were greatly conserved to ensure the building of a specific conformation. Substitutions, which may be neutral or selective, occurred in precise positions. Virtually all vertebrate species possess an oxytocin-like and a vasopressin-like peptide so that two evolutionary lineages can be traced. Because a single peptide, vasotocin ([Ile3]-vasopressin or [Arg8]-oxytocin) has been found in the most primitive Cyclostomata, a primordial gene duplication and subsequent mutations are assumed to have given rise to the two lineages. They started with vasotocin and isotocin ([Ser4,Ile8]-oxytocin) in bony fishes and culminated with vasopressin and oxytocin in placental mammals. Mesotocin ([Ile3]-oxytocin), found in lungfishes, amphibians, reptiles, birds and marsupials, appears as an evolutionary intermediate. The change from isotocin ([Ser4,Ile8]-oxytocin) into mesotocin ([Ile8]-oxytocin), can be observed in African and Australian lungfishes, species making the transition from bony fishes to land vertebrates. On the other hand the replacement of mesotocin by oxytocin can be detected in marsupials, particularly in the North-American opossum and the Australian Northern bandicoot that have both mesotocin and oxytocin whereas placental mammals possess only oxytocin. The invariability of this peptide in placentals can be explained by receptor-fitting selective pressure. In contrast to bony vertebrates in which neurohypophysial hormones revealed a remarkable structural stability, cartilaginous fishes displayed an unique oxytocin-like hormone evolution with variability and duality. Aside from vasotocin, in the subclass Selachii, rays have

Opposing Oxytocin Effects on Intergroup Cooperative Behavior in Intuitive and Reflective Minds.

PubMed

Ma, Yina; Liu, Yi; Rand, David G; Heatherton, Todd F; Han, Shihui

2015-09-01

People often favor ingroup over outgroup members when choosing to cooperate. Such ingroup-favored cooperation is promoted by oxytocin-a neuropeptide shown to facilitate social cognition and that has emerged as a pharmacological target for treatments of social functioning deficits. The current study applied a dual-process model to investigate whether and how intuitive and reflective cognitive styles affect the oxytocin-motivated ingroup favoritism in cooperation. We examined oxytocin effects on ingroup favoritism in a double-blind, placebo-controlled between-subjects design where cognitive processing (intuition vs reflection) was experimentally manipulated in healthy Chinese males (n=150). We also supplemented this experimental manipulation with an individual difference analysis by assessing participants' inclination toward intuition or reflection in daily life. Intranasal administration of oxytocin (vs placebo) increased ingroup favoritism among participants primed to be intuitive or those who preferred intuition in daily life. In contrast, oxytocin decreased ingroup favoritism in participants primed to rely on reflective thinking or those who preferred reflective decision-making in daily life. Our results demonstrate that oxytocin has distinct functional roles when different cognitive styles (ie, intuition vs reflection) are promoted during social cooperation in a group situation. Our findings have implications for oxytocin pharmacotherapy of social dysfunction in that whether the effects of oxytocin on social functioning are facilitative, debilitative, or null, depends on an individual's cognitive style.

Continuous and selective measurement of oxytocin and vasopressin using boron-doped diamond electrodes

NASA Astrophysics Data System (ADS)

Asai, Kai; Ivandini, Tribidasari A.; Einaga, Yasuaki

2016-09-01

The electrochemical detection of oxytocin using boron-doped diamond (BDD) electrodes was studied. Cyclic voltammetry of oxytocin in a phosphate buffer solution exhibits an oxidation peak at +0.7 V (vs. Ag/AgCl), which is attributable to oxidation of the phenolic group in the tyrosyl moiety. Furthermore, the linearity of the current peaks obtained in flow injection analysis (FIA) using BDD microelectrodes over the oxytocin concentration range from 0.1 to 10.0 μM with a detection limit of 50 nM (S/N = 3) was high (R2 = 0.995). Although the voltammograms of oxytocin and vasopressin observed with an as-deposited BDD electrode, as well as with a cathodically-reduced BDD electrode, were similar, a clear distinction was observed with anodically-oxidized BDD electrodes due to the attractive interaction between vasopressin and the oxidized BDD surface. By means of this distinction, selective measurements using chronoamperometry combined with flow injection analysis at an optimized potential were demonstrated, indicating the possibility of making selective in situ or in vivo measurements of oxytocin.

Effect of Intranasal Oxytocin Administration on Psychiatric Symptoms: A Meta-Analysis of Placebo-Controlled Studies

PubMed Central

Hofmann, Stefan G.; Fang, Angela; Brager, Daniel N.

2015-01-01

Clinical trials of intranasal administration of oxytocin for treating psychiatric problems have yielded mixed results. To conduct a quantitative review of placebo-controlled clinical trials of intranasally-administered oxytocin (OT) for psychiatric symptoms, manual and electronic searches using PubMed and PsycINFO were conducted. Of 1,828 entries, 16 placebo-controlled studies totaling 330 participants were included in the analysis. The overall placebo-controlled effect size was moderately strong (Hedges’ g = 0.67) and robust as suggested by the fail-safe N and funnel plot analysis. OT reduced symptoms of depression, anxiety, autism/repetitive behaviors, psychotic symptoms, and general psychopathology. In the combined sample, symptom reduction was moderated by frequency of administration. Publication year and diagnostic category did not moderate the effect of OT on the clinical outcome measures. We conclude that intranasal administration of OT is a potentially useful intervention for reducing psychiatric symptoms. However, more studies are needed to determine the best treatment target and to identify the mechanism of treatment change. PMID:26094200

Genetic modulation of oxytocin sensitivity: a pharmacogenetic approach

PubMed Central

Chen, F S; Kumsta, R; Dvorak, F; Domes, G; Yim, O S; Ebstein, R P; Heinrichs, M

2015-01-01

Intranasal administration of the neuropeptide oxytocin has been shown to influence a range of complex social cognitions and social behaviors, and it holds therapeutic potential for the treatment of mental disorders characterized by social functioning deficits such as autism, social phobia and borderline personality disorder. However, considerable variability exists in individual responses to oxytocin administration. Here, we undertook a study to investigate the role of genetic variation in sensitivity to exogenous oxytocin using a socioemotional task. In a randomized, double-blind, placebo-controlled experiment with a repeated-measures (crossover) design, we assessed the performance of 203 men on an emotion recognition task under oxytocin and placebo. We took a haplotype-based approach to investigate the association between oxytocin receptor gene variation and oxytocin sensitivity. We identified a six-marker haplotype block spanning the promoter region and intron 3 that was significantly associated with our measure of oxytocin sensitivity. Specifically, the TTCGGG haplotype comprising single-nucleotide polymorphisms rs237917–rs2268498–rs4564970–rs237897–rs2268495–rs53576 is associated with increased emotion recognition performance under oxytocin versus placebo, and the CCGAGA haplotype with the opposite pattern. These results on the genetic modulation of sensitivity to oxytocin document a significant source of individual differences with implications for personalized treatment approaches using oxytocin administration. PMID:26506050

Oxytocin in animal models of autism spectrum disorder.

PubMed

Peñagarikano, Olga

2017-02-01

Autism spectrum disorder is a behavioral disorder characterized by impairments in social interaction and communication together with the presence of stereotyped behaviors and restricted interests. Although highly genetic, its etiology is complex which correlates with the extensive heterogeneity found in its clinical manifestation, adding to the challenge of understanding its pathophysiology and develop targeted pharmacotherapies. The neuropeptide oxytocin is part of a highly conserved system involved in the regulation of social behavior, and both animal and human research have shown that variation in the oxytocin system accounts for interindividual differences in the expression of social behaviors in mammals. In autism, recent studies in human patients and animal models are starting to reveal that alterations in the oxytocin system are more common than previously anticipated. Genetic variation in the key players involved in the system (i.e., oxytocin receptor, oxytocin, and CD38) has been found associated with autism in humans, and animal models of the disorder converge in an altered oxytocin system and/or dysfunction in oxytocin related biological processes. Furthermore, oxytocin administration exerts a behavioral and neurobiological response, and thus, the oxytocin system has become a promising potential therapeutical target for autism. Animal models represent a valuable tool to aid in the research into the potential therapeutic use of oxytocin. In this review, I aim to discuss the main findings related to oxytocin research in autism with a focus on findings in animal models. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 202-213, 2017. © 2016 Wiley Periodicals, Inc.

Interaction of oxytocin level and past depression may predict postpartum depressive symptom severity

PubMed Central

Massey, Suena H.; Schuette, Stephanie A.; Pournajafi-Nazarloo, Hossein; Wisner, Katherine L.; Carter, C. Sue

2016-01-01

Purpose We examined plasma oxytocin concentration and postpartum depression (PPD) symptom severity in women who were not depressed during pregnancy, and whether this differed by major depressive disorder (MDD) history. Methods We assessed psychiatric history and plasma oxytocin in 66 healthy pregnant women in the third trimester (M = 35 ± 3 weeks) and depressive symptoms at 6 weeks postpartum (M = 5.9 ± 0.8 weeks). Linear regression analysis was used to examine oxytocin and PPD symptom severity, and moderation of oxytocin and PPD by past MDD. Results Women with (n = 13) and without (n = 53) past MDD differed in third trimester depressive symptom severity, but not oxytocin level, demographic factors or birth outcomes. Controlling for third trimester depressive symptoms, oxytocin level was unrelated to PPD symptom severity [B(SE) = −.019(.084); β = −.025; t = −.227; p = .821]. However, oxytocin level interacted with past MDD to predict PPD symptom severity [(B(SE) = 7.489(2.429); β = .328; t = 3.084; p = .003]. Higher oxytocin predicted greater PPD symptom severity in women with past MDD (p = .019), but not in women without (p = .216). Conclusions Replication in a larger sample and methodologic challenges are discussed. PMID:26957508

Outcome of misoprostol and oxytocin in induction of labour

PubMed Central

Acharya, Trishna; Devkota, Ramesh; Bhattarai, Bimbishar; Acharya, Radha

2017-01-01

Background: Induction of labour is the process of initiating the labour by artificial means from 24 weeks of gestation. The main aim of this study is to find out the maternal and foetal outcomes after induction of labour with misoprostol and oxytocin beyond 37 weeks of gestation. Methods: This was a hospital-based observational study carried out at Paropakar Maternity and Women’s Hospital, Nepal. Misoprostol of 25 µg was inserted in posterior fornix of vagina or oxytocin infusion was started from 2.5 units on whom induction was decided. Maternal and foetal/neonatal outcomes were observed. Collected data were analysed using SPSS and MS Excel. Results: General induction rate was found to be 7.2%. In this study, post-term pregnancy was found to be the most common reason for induction of labour. Analysis of onset of labour led to the finding that mean onset of labour was much rapid in oxytocin (6.6 h) than misoprostol (13.6 h). However, there is similarity in induction–delivery interval in both groups. Overall, the rate of normal delivery and caesarean section was found to be 64.9% and 33.2%, respectively. Similarly, normal delivery within 12 h was seen in 18.4% of the patients given with misoprostol and 43.5% in oxytocin group. Foetal distress was found as the most common reason for caesarean section. The overall occurrence of maternal complication was found to be similar in misoprostol and oxytocin groups, nausea/vomiting being the most common (36.7%) complication followed by fever (24.1%). Besides this, the most common neonatal complication found in overall cases was meconium stained liquor (49.2%). Conclusion: It was found that misoprostol was used most frequently for induction of labour compared to oxytocin. The onset of labour was found to be rapid in oxytocin than misoprostol. However, the occurrence of side effects was found to be similar in both misoprostol and oxytocin groups. PMID:28540049

Oxytocin administration enhances controlled social cognition in patients with schizophrenia

PubMed Central

Woolley, J.D.; Chuang, B.; Lam, O.; Lai, W.; O’Donovan, A.; Rankin, K.P.; Mathalon, D.H.; Vinogradov, S.

2014-01-01

Summary Background Individuals with schizophrenia have functionally significant deficits in automatic and controlled social cognition, but no currently available pharmacologic treatments reduce these deficits. The neuropeptide oxytocin has multiple prosocial effects when administered intranasally in humans and there is growing interest in its therapeutic potential in schizophrenia. Methods We administered 40 IU of oxytocin and saline placebo intranasally to 29 male subjects with schizophrenia and 31 age-matched, healthy controls in a randomized, double-blind, placebo-controlled, cross-over study. Social cognition was assessed with The Awareness of Social Inference Test (TASIT) and the Reading the Mind in the Eyes Test (RMET). We examined the effects of oxytocin administration on automatic social cognition (the ability to rapidly interpret and understand emotional cues from the voice, face, and body); controlled social cognition (the ability to comprehend indirectly expressed emotions, thoughts, and intentions through complex deliberations over longer time periods); and a control task (the ability to comprehend truthful dialog and perform general task procedures) in individuals with and without schizophrenia using mixed factorial analysis of variance models. Results Patients with schizophrenia showed significant impairments in automatic and controlled social cognition compared to healthy controls, and administration of oxytocin significantly improved their controlled, but not automatic, social cognition, F(1, 58) = 8.75; p = 0.004. Conversely, oxytocin administration had limited effects on social cognition in healthy participants. Patients and controls performed equally well and there were no effects of oxytocin administration on the control task. Discussion Intact social cognitive abilities are associated with better functional outcomes in individuals with schizophrenia. Our data highlight the potentially complex effects of oxytocin on some but not all aspects of

[Effect of oxytocin on human pain perception].

PubMed

Pfeifer, A-C; Ditzen, B; Neubauer, E; Schiltenwolf, M

2016-10-01

Over the years the effect of the neuropeptide oxytocin and its possible utilization for pain management has been increasingly more investigated and discussed. Initial results emphasized the effects of oxytocin with respect to labor and breastfeeding. Diverse animals studies were also able to demonstrate the effectiveness of the peptide in attachment behavior and pain perception; however, it is still unclear how oxytocin affects pain perception in humans. The potential therapeutic effectiveness of oxytocin could be particularly important for primary and secondary treatment of pain patients because chronification of pain can occur more frequently in this area. For this review the databases PubMed, Medline und PsycINFO were searched using the terms oxytocin, pain, human and analgesic. The search resulted in a total of 89 original articles after excluding articles regarding labor pain, breastfeeding and animal studies. Only those studies were included which were carried out between 1994 and 2015. A total of 17 articles remained for inclusion in this review and included 13 studies on the exogenous application of oxytocin and 4 on measurement of oxytocin levels in plasma. This review article gives a summary of the current state of research on oxytocin and its direct and indirect association with human pain perception and emphasizes its relevance for the multimodal management of pain.

Preventing PTSD with oxytocin: effects of oxytocin administration on fear neurocircuitry and PTSD symptom development in recently trauma-exposed individuals

PubMed Central

Frijling, Jessie L.

2017-01-01

ABSTRACT 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 symptom development, as oxytocin administration was previously found to beneficially impact neurobiological (e.g. amygdala reactivity) and socio-emotional PTSD vulnerability factors. Objective: The overall aim of this dissertation was to investigate the potential of intranasal oxytocin administration as early preventive intervention for PTSD. Methods: We performed a functional magnetic resonance imaging (fMRI) study to assess the acute effects of a single administration of oxytocin on the functional fear neurocircuitry – consisting of the amygdala and (pre)frontal brain regions – in recently trauma-exposed emergency department patients (range n = 37–41). In addition, we performed a multicentre randomized double-blind placebo-controlled clinical trial (RCT) to assess the efficacy of repeated intranasal oxytocin administration early after trauma for preventing PTSD symptom development up to six months posttrauma (n = 107). Results: In our fMRI experiments we observed acutely increased amygdala reactivity to fearful faces and attenuated amygdala-ventromedial and ventrolateral prefrontal cortex functional connectivity after a single oxytocin administration in recently trauma-exposed individuals. However, in our RCT we found that repeated intranasal oxytocin administration early posttrauma reduced subsequent PTSD symptom development in recently trauma-exposed emergency department patients with high acute PTSD symptoms. Conclusions: These findings indicate that repeated intranasal oxytocin is a promising early preventive intervention for PTSD for individuals at increased risk for PTSD due to high acute symptom severity. Administration frequency dependent

Oxytocin promotes group-serving dishonesty.

PubMed

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.

Oxytocin promotes group-serving dishonesty

PubMed Central

Shalvi, Shaul; De Dreu, Carsten K. W.

2014-01-01

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. PMID:24706799

Effects of Oxytocin on Neural Response to Facial Expressions in Patients with Schizophrenia

PubMed Central

Shin, Na Young; Park, Hye Yoon; Jung, Wi Hoon; Park, Jin Woo; Yun, Je-Yeon; Jang, Joon Hwan; Kim, Sung Nyun; Han, Hyun Jung; Kim, So-Yeon; Kang, Do-Hyung; Kwon, Jun Soo

2015-01-01

Impaired facial emotion recognition is a core deficit in schizophrenia. Oxytocin has been shown to improve social perception in patients with schizophrenia; however, the effect of oxytocin on the neural activity underlying facial emotion recognition has not been investigated. This study was aimed to assess the effect of a single dose of intranasal oxytocin on brain activity in patients with schizophrenia using an implicit facial emotion-recognition paradigm. Sixteen male patients with schizophrenia and 16 age-matched healthy male control subjects participated in a randomized, double-blind, placebo-controlled crossover trial at Seoul National University Hospital. Delivery of a single dose of 40 IU intranasal oxytocin and the placebo was separated by 1 week. Drug conditions were compared by performing a region of interest (ROI) analysis of the bilateral amygdala on responses to the emotion recognition test. It was found that nasal spray decreased amygdala activity for fearful emotion and increased activity for happy faces. Further, oxytocin elicited differential effects between the patient and control groups. Intranasal oxytocin attenuated amygdala activity for emotional faces in patients with schizophrenia, whereas intranasal oxytocin significantly increased amygdala activity in healthy controls. Oxytocin-induced BOLD signal changes in amygdala in response to happy faces was related to attachment style in the control group. Our result provides new evidence of a modulatory effect of oxytocin on neural response to emotional faces for patients with schizophrenia. Future studies are needed to investigate the effectiveness of long-term treatment with intranasal oxytocin on neural activity in patients with schizophrenia. PMID:25666311

Effects of Oxytocin on Neural Response to Facial Expressions in Patients with Schizophrenia.

PubMed

Shin, Na Young; Park, Hye Yoon; Jung, Wi Hoon; Park, Jin Woo; Yun, Je-Yeon; Jang, Joon Hwan; Kim, Sung Nyun; Han, Hyun Jung; Kim, So-Yeon; Kang, Do-Hyung; Kwon, Jun Soo

2015-07-01

Impaired facial emotion recognition is a core deficit in schizophrenia. Oxytocin has been shown to improve social perception in patients with schizophrenia; however, the effect of oxytocin on the neural activity underlying facial emotion recognition has not been investigated. This study was aimed to assess the effect of a single dose of intranasal oxytocin on brain activity in patients with schizophrenia using an implicit facial emotion-recognition paradigm. Sixteen male patients with schizophrenia and 16 age-matched healthy male control subjects participated in a randomized, double-blind, placebo-controlled crossover trial at Seoul National University Hospital. Delivery of a single dose of 40 IU intranasal oxytocin and the placebo was separated by 1 week. Drug conditions were compared by performing a region of interest (ROI) analysis of the bilateral amygdala on responses to the emotion recognition test. It was found that nasal spray decreased amygdala activity for fearful emotion and increased activity for happy faces. Further, oxytocin elicited differential effects between the patient and control groups. Intranasal oxytocin attenuated amygdala activity for emotional faces in patients with schizophrenia, whereas intranasal oxytocin significantly increased amygdala activity in healthy controls. Oxytocin-induced BOLD signal changes in amygdala in response to happy faces was related to attachment style in the control group. Our result provides new evidence of a modulatory effect of oxytocin on neural response to emotional faces for patients with schizophrenia. Future studies are needed to investigate the effectiveness of long-term treatment with intranasal oxytocin on neural activity in patients with schizophrenia.

Oxytocin improves synchronisation in leader-follower interaction.

PubMed

Gebauer, L; Witek, M A G; Hansen, N C; Thomas, J; Konvalinka, I; Vuust, P

2016-12-08

The neuropeptide oxytocin has been shown to affect social interaction. Meanwhile, the underlying mechanism remains highly debated. Using an interpersonal finger-tapping paradigm, we investigated whether oxytocin affects the ability to synchronise with and adapt to the behaviour of others. Dyads received either oxytocin or a non-active placebo, intranasally. We show that in conditions where one dyad-member was tapping to another unresponsive dyad-member - i.e. one was following another who was leading/self-pacing - dyads given oxytocin were more synchronised than dyads given placebo. However, 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 partner's behaviour through a reduction in tapping-variability. Hence, oxytocin may facilitate social interaction by enhancing sensorimotor predictions supporting interpersonal synchronisation. The study thus provides novel perspectives on how neurobiological processes relate to socio-psychological behaviour and contributes to the growing evidence that synchronisation and prediction are central to social cognition.

Oxytocin improves synchronisation in leader-follower interaction

PubMed Central

Gebauer, L.; Witek, M. A. G.; Hansen, N. C.; Thomas, J.; Konvalinka, I.; Vuust, P.

2016-01-01

The neuropeptide oxytocin has been shown to affect social interaction. Meanwhile, the underlying mechanism remains highly debated. Using an interpersonal finger-tapping paradigm, we investigated whether oxytocin affects the ability to synchronise with and adapt to the behaviour of others. Dyads received either oxytocin or a non-active placebo, intranasally. We show that in conditions where one dyad-member was tapping to another unresponsive dyad-member – i.e. one was following another who was leading/self-pacing – dyads given oxytocin were more synchronised than dyads given placebo. However, 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 partner’s behaviour through a reduction in tapping-variability. Hence, oxytocin may facilitate social interaction by enhancing sensorimotor predictions supporting interpersonal synchronisation. The study thus provides novel perspectives on how neurobiological processes relate to socio-psychological behaviour and contributes to the growing evidence that synchronisation and prediction are central to social cognition. PMID:27929100

Oxytocin and Maternal Brain Plasticity.

PubMed

Kim, Sohye; Strathearn, Lane

2016-09-01

Although dramatic postnatal changes in maternal behavior have long been noted, we are only now beginning to understand the neurobiological mechanisms that support this transition. The present paper synthesizes growing insights from both animal and human research to provide an overview of the plasticity of the mother's brain, with a particular emphasis on the oxytocin system. We examine plasticity observed within the oxytocin system and discuss how these changes mediate an array of other adaptations observed within the maternal brain. We outline factors that affect the oxytocin-mediated plasticity of the maternal brain and review evidence linking disruptions in oxytocin functions to challenges in maternal adaptation. We conclude by suggesting a strategy for intervention with mothers who may be at risk for maladjustment during this transition to motherhood, while highlighting areas where further research is needed. © 2016 Wiley Periodicals, Inc.

Oxytocin for labour and caesarean delivery: implications for the anaesthesiologist.

PubMed

Dyer, Robert A; Butwick, Alexander J; Carvalho, Brendan

2011-06-01

The implications of the obstetric use of oxytocin for obstetric anaesthesia practice are summarised. The review focuses on recent research on the uterotonic effects of oxytocin for prophylaxis and management of uterine atony during caesarean delivery. Oxytocin remains the first-line agent in the prevention and management of uterine atony. In-vitro and in-vivo studies show that prior exposure to oxytocin induces uterine muscle oxytocin receptor desensitization. This may influence oxytocin dosing for adequate uterine tone following delivery. Oxytocin has important cardiovascular side-effects (hypotension, tachycardia and myocardial ischaemia). Recent studies suggest that the effective dose of oxytocin for prophylaxis against uterine atony during caesarean delivery is significantly lower than the 5-10 IU historically used by anaesthesiologists. Slow administration of small bolus doses of oxytocin minimises maternal haemodynamic disturbance. Continuous oxytocin infusions are recommended for maintaining uterine tone after bolus administration, although ideal infusion rates are still to be established. The efficacy of the long-acting oxytocin analogue carbetocin requires further investigation. Recommendations are presented for oxytocin dosing during caesarean delivery. Oxytocin remains the first-line uterotonic after vaginal and caesarean delivery. Recent research elucidates the therapeutic range of oxytocin during caesarean delivery, as well as receptor desensitization. Evidenced-based protocols for the prevention and treatment of uterine atony during caesarean delivery are recommended.

Adiponectin selectively inhibits oxytocin neurons of the paraventricular nucleus of the hypothalamus

PubMed Central

Hoyda, Ted D; Fry, Mark; Ahima, Rexford S; Ferguson, Alastair V

2007-01-01

Adiponectin is an adipocyte derived hormone which acts in the brain to modulate energy homeostasis and autonomic function. The paraventricular nucleus of the hypothalamus (PVN) which plays a key role in controlling pituitary hormone secretion has been suggested to be a central target for adiponectin actions. A number of hormones produced by PVN neurons have been implicated in the regulation of energy homeostasis including oxytocin, corticotropin releasing hormone and thyrotropin releasing hormone. In the present study we investigated the role of adiponectin in controlling the excitability of magnocellular (MNC – oxytocin or vasopressin secreting) neurons within the PVN. Using RT-PCR techniques we have shown expression of both adiponectin receptors in the PVN. Patch clamp recordings from MNC neurons in hypothalamic slices have also identified mixed (27% hyperpolarization, 42% depolarization) effects of adiponectin in modulating the excitability of the majority of MNC neurons tested. These effects are maintained when cells are placed in synaptic isolation using tetrodotoxin. Additionally we combined electrophysiological recordings with single cell RT-PCR to examine the actions of adiponectin on MNC neurons which expressed oxytocin only, vasopressin only, or both oxytocin and vasopressin mRNA and assess the profile of receptor expression in these subgroups. Adiponectin was found to hyperpolarize 100% of oxytocin neurons tested (n = 6), while vasopressin cells, while all affected (n = 6), showed mixed responses. Further analysis indicates oxytocin neurons express both receptors (6/7) while vasopressin neurons express either both receptors (3/8) or one receptor (5/8). In contrast 6/6 oxytocin/vasopressin neurons were unaffected by adiponectin. Co-expressing oxytocin and vasopressin neurons express neither receptor (4/6). The results presented in this study suggest that adiponectin plays specific roles in controlling the excitability oxytocin secreting neurons, actions

Oxytocin Enhances Social Persuasion during Hypnosis

PubMed Central

Bryant, Richard A.; Hung, Lynette

2013-01-01

It has long been argued that hypnosis cannot promote behaviors that people will not otherwise engage in. Oxytocin can enhance trust in others, and may promote the extent to which a hypnotized person complies with the suggestion of a hypnotist. This double-blind placebo study administered oxytocin or placebo to high hypnotizable participants (N = 28), who were then administered hypnotic suggestions for socially unorthodox behaviors, including swearing during the experiment, singing out loud, and dancing in response to a posthypnotic cue. Participants who received oxytocin were significantly more likely to swear and dance than those who received the placebo. This finding may be interpreted in terms of oxytocin increasing social compliance in response as a function of (a) increased trust in the hypnotist, (b) reduced social anxiety, or (c) enhanced sensitivity to cues to respond to experimental expectations. These results point to the potential role of oxytocin in social persuasion. PMID:23577153

Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial

PubMed Central

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

2016-01-01

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. PMID:27552585

Oxytocin efficacy is modulated by dosage and oxytocin receptor genotype in young adults with high-functioning autism: a 24-week randomized clinical trial.

PubMed

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.

Oxytocin reduces cocaine seeking and reverses chronic cocaine-induced changes in glutamate receptor function.

PubMed

Zhou, Luyi; Sun, Wei-Lun; Young, Amy B; Lee, Kunhee; McGinty, Jacqueline F; See, Ronald E

2014-10-31

Oxytocin, a neurohypophyseal neuropeptide, is a potential mediator and regulator of drug addiction. However, the cellular mechanisms of oxytocin in drug seeking remain unknown. In the present study, we used a self-administration/reinstatement model to study the effects of oxytocin on cocaine seeking and its potential interaction with glutamate function at the receptor level. Systemic oxytocin dose-dependently reduced cocaine self-administration during various schedules of reinforcement, including fixed ratio 1, fixed ratio 5, and progressive ratio. Oxytocin also attenuated reinstatement to cocaine seeking induced by cocaine prime or conditioned cues. Western-blot analysis indicated that oxytocin increased phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor GluA1 subunit at the Ser 845 site with or without accompanying increases in phosphorylation of extracellular signal-regulated kinase, in several brain regions, including the prefrontal cortex, bed nucleus of the stria terminalis, amygdala, and dorsal hippocampus. Immunoprecipitation of oxytocin receptor and GluA1 subunit receptors further demonstrated a physical interaction between these 2 receptors, although the interaction was not influenced by chronic cocaine or oxytocin treatment. Oxytocin also attenuated sucrose seeking in a GluA1- or extracellular-signal-regulated kinase-independent manner. These findings suggest that oxytocin mediates cocaine seeking through interacting with glutamate receptor systems via second messenger cascades in mesocorticolimbic regions. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

[Oxytocin administration during labor. Results from the 2010 French National Perinatal Survey].

PubMed

Belghiti, J; Coulm, B; Kayem, G; Blondel, B; Deneux-Tharaux, C

2013-11-01

To estimate the frequency of oxytocin administration during labor, in all women in labor, in low-risk women, and in women with a previous cesarean delivery. Our objectives were also to identify characteristics of women and of maternity units associated with this practice in France. Analysis of the 2010 French Perinatal Survey data (n=14,681 women who delivered in continental France). The frequency of oxytocin administration during labor was estimated in all women in labor (n=12,845) and in low-risk women (n=9798). The independent associations between oxytocin administration during labor and characteristics of women and units were quantified with multivariate logistic regression modeling. Sixty-four percent of laboring women received oxytocin during labor, and 58% of women with a spontaneous onset of labor. In the population of low-risk women with spontaneous labor and epidural, nulliparity and over-weight, as well as the private status and small size of the maternity unit, were independently associated with a more frequent administration of oxytocin during labor. Oxytocin administration during labor is very frequent in France, probably beyond classical indications. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Inhaled oxytocin increases positive social behaviors in newborn macaques

PubMed Central

Simpson, Elizabeth A.; Sclafani, Valentina; Paukner, Annika; Hamel, Amanda F.; Novak, Melinda A.; Meyer, Jerrold S.; Suomi, Stephen J.; Ferrari, Pier Francesco

2014-01-01

Early caregiver–infant interactions are critical for infants’ socioemotional and cognitive development. Several hormones and neuromodulators, including oxytocin, affect these interactions. Exogenous oxytocin promotes social behaviors in several species, including human and nonhuman primates. Although exogenous oxytocin increases social function in adults—including expression recognition and affiliation—it is unknown whether oxytocin can increase social interactions in infants. We hypothesized that nebulized oxytocin would increase affiliative social behaviors and such effects would be modulated by infants’ social skills, measured earlier in development. We also hypothesized that oxytocin’s effects on social behaviors may be due to its anxiolytic effects. We tested these hypotheses in a blind study by nebulizing 7- to 14-d-old macaques (n = 28) with oxytocin or saline. Following oxytocin administration, infants’ facial gesturing at a human caregiver increased, and infants’ salivary oxytocin was positively correlated with the time spent in close proximity to a caregiver. Infants’ imitative skill (measured earlier in development: 1–7 d of age) predicted oxytocin-associated increases in affiliative behaviors—lip smacking, visual attention to a caregiver, and time in close proximity to a caregiver—suggesting that infants with higher propensities for positive social interactions are more sensitive to exogenous oxytocin. Oxytocin also decreased salivary cortisol, but not stress-related behaviors (e.g., scratching), suggesting the possibility of some anxiolytic effects. To our knowledge, this study provides the first evidence that oxytocin increases positive social behaviors in newborns. This information is of critical importance for potential interventions aimed at ameliorating inadequate social behaviors in infants with higher likelihood of developing neurodevelopmental disorder. PMID:24778211

Oxytocin improves emotion recognition for older males.

PubMed

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.

Opposing Oxytocin Effects on Intergroup Cooperative Behavior in Intuitive and Reflective Minds

PubMed Central

Ma, Yina; Liu, Yi; Rand, David G; Heatherton, Todd F; Han, Shihui

2015-01-01

People often favor ingroup over outgroup members when choosing to cooperate. Such ingroup-favored cooperation is promoted by oxytocin—a neuropeptide shown to facilitate social cognition and that has emerged as a pharmacological target for treatments of social functioning deficits. The current study applied a dual-process model to investigate whether and how intuitive and reflective cognitive styles affect the oxytocin-motivated ingroup favoritism in cooperation. We examined oxytocin effects on ingroup favoritism in a double-blind, placebo-controlled between-subjects design where cognitive processing (intuition vs reflection) was experimentally manipulated in healthy Chinese males (n=150). We also supplemented this experimental manipulation with an individual difference analysis by assessing participants' inclination toward intuition or reflection in daily life. Intranasal administration of oxytocin (vs placebo) increased ingroup favoritism among participants primed to be intuitive or those who preferred intuition in daily life. In contrast, oxytocin decreased ingroup favoritism in participants primed to rely on reflective thinking or those who preferred reflective decision-making in daily life. Our results demonstrate that oxytocin has distinct functional roles when different cognitive styles (ie, intuition vs reflection) are promoted during social cooperation in a group situation. Our findings have implications for oxytocin pharmacotherapy of social dysfunction in that whether the effects of oxytocin on social functioning are facilitative, debilitative, or null, depends on an individual's cognitive style. PMID:25807529

Safety, Tolerability and Pharmacokinetics of Single Doses of Oxytocin Administered via an Inhaled Route in Healthy Females: Randomized, Single-blind, Phase 1 Study.

PubMed

Fernando, Disala; Siederer, Sarah; Singh, Sunita; Schneider, Ian; Gupta, Ashutosh; Powell, Marcy; Richards, Duncan; McIntosh, Michelle P; Lambert, Peter; Fowles, Susan

2017-08-01

The utility of intramuscular (IM) oxytocin for the prevention of postpartum hemorrhage in resource-poor settings is limited by the requirement for temperature-controlled storage and skilled staff to administer the injection. We evaluated the safety, tolerability and pharmacokinetics (PK) of a heat-stable, inhaled (IH) oxytocin formulation. This phase 1, randomized, single-center, single-blind, dose-escalation, fixed-sequence study (NCT02542813) was conducted in healthy, premenopausal, non-pregnant, non-lactating women aged 18-45years. Subjects initially received IM oxytocin 10 international units (IU) on day 1, IH placebo on day 2, and IH oxytocin 50μg on day 3. Subjects were then randomized 4:1 using validated GSK internal software to IH placebo or ascending doses of IH oxytocin (200, 400, 600μg). PK was assessed by comparing systemic exposure (maximum observed plasma concentration, area under the concentration-time curve, and plasma concentrations at 10 and 30min post dose) for IH versus IM oxytocin. Adverse events (AEs), spirometry, laboratory tests, vital signs, electrocardiograms, physical examinations, and cardiac telemetry were assessed. Subjects were recruited between September 14, 2015 and October 12, 2015. Of the 16 subjects randomized following initial dosing, 15 (IH placebo n=3; IH oxytocin n=12) completed the study. IH (all doses) and IM oxytocin PK profiles were comparable in shape. However, systemic exposure with IH oxytocin 400μg most closely matched IM oxytocin 10IU. Systemic exposure was approximately dose proportional for IH oxytocin. No serious AEs were reported. No clinically significant findings were observed for any safety parameters. These data suggest that similar oxytocin systemic exposure can be achieved with IM and IH administration routes, and no safety concerns were identified with either route. The inhalation route may offer the opportunity to increase access to oxytocin for women giving birth in resource-poor settings. Copyright �

The oxytocin receptor gene (OXTR) is associated with autism spectrum disorder: a meta-analysis.

PubMed

LoParo, D; Waldman, I D

2015-05-01

The oxytocin receptor gene (OXTR) has been studied as a risk factor for autism spectrum disorder (ASD) owing to converging evidence from multiple levels of analysis that oxytocin (OXT) has an important role in the regulation of affiliative behavior and social bonding in both nonhuman mammals and humans. Inconsistency in the effect sizes of the OXTR variants included in association studies render it unclear whether OXTR is truly associated with ASD, and, if so, which OXTR single-nucleotide polymorphisms (SNPs) are associated. Thus, a meta-analytic review of extant studies is needed to determine whether OXTR shows association with ASD, and to elucidate which specific SNPs have a significant effect on ASD. The current meta-analysis of 16 OXTR SNPs included 3941 individuals with ASD from 11 independent samples, although analyses of each individual SNP included a subset of this total. We found significant associations between ASD and the SNPs rs7632287, rs237887, rs2268491 and rs2254298. OXTR was also significantly associated with ASD in a gene-based test. The current meta-analysis is the largest and most comprehensive investigation of the association of OXTR with ASD and the findings suggest directions for future studies of the etiology of ASD.

Molecular Mechanisms of Antidiuretic Effect of Oxytocin

PubMed Central

Li, Chunling; Wang, Weidong; Summer, Sandra N.; Westfall, Timothy D.; Brooks, David P.; Falk, Sandor; Schrier, Robert W.

2008-01-01

Oxytocin is known to have an antidiuretic effect, but the mechanisms underlying this effect are not completely understood. We infused oxytocin by osmotic minipump into vasopressin-deficient Brattleboro rats for five days and observed marked antidiuresis, increased urine osmolality, and increased solute-free water reabsorption. Administration of oxytocin also significantly increased the protein levels of aquaporin-2 (AQP2), phosphorylated AQP2 (p-AQP2), and AQP3 in the inner medulla and in the outer medulla plus cortex. Immunohistochemistry demonstrated increased AQP2 and p-AQP2 expression and trafficking to the apical plasma membrane of principal cells in the collecting duct, and increased AQP3 expression in the basolateral membrane. These oxytocin-induced effects were blocked by treatment with the vasopressin V2 receptor antagonist SR121463B, but not by treatment with the oxytocin receptor antagonist GW796679X. We conclude that vasopressin V2 receptors mediate the antidiuretic effects of oxytocin, including increased expression and apical trafficking of AQP2, p-AQP2, and increased AQP3 protein expression. PMID:18057218

Randomised controlled trial of oxytocin alone versus oxytocin and ergometrine in active management of third stage of labour.

PubMed Central

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 OUTCOME MEASURES--Postpartum haemorrhage, nausea, vomiting, and increased blood pressure. RESULTS--3497 women were randomly allocated to receive oxytocin-ergometrine (n = 1730) or oxytocin (n = 1753). Rates of postpartum haemorrhage (> or = 500 ml or > or = 1000 ml) were similar in both arms (odds ratio 0.90 (0.82); 95% confidence interval 0.75 to 1.07 (0.59 to 1.14) at 500 ml (1000 ml) threshold). The use of oxytocin-ergometrine was associated with nausea, vomiting, and increased blood pressure. CONCLUSIONS--There are few advantages but several disadvantages for the routine use of oxytoxinergometrine when prophylactic active management of the third stage of labour is practised. Further investigation of dose-response for oxytocin may be warranted. PMID:8251842

[Oxytocin, the hormone that everyone uses and that few know].

PubMed

López-Ramírez, Cinthia Elizabeth; Arámbula-Almanza, Jaqueline; Camarena-Pulido, Eva Elizabet

2014-07-01

BACKGROUND. Oxytocin is a well known drug most commonly used in obstetrics for induction or augmentation of labor. Due to its essential role in labor, and the overall effect in the body, oxytocin must be deeply understood by all obstetricians who use it and prescribe it. There is relevant data listed about oxytocin and has reviewed the evidence in 31 full text articles of indexed journals between 1999 and 2013. In search engines like MEDLINE, MedicLatina, PUBMED, Wolters Kluwer Healt, with keywords like: oxytocin, oxytocin receptor, oxytocin vasopressin, oxytocin postpartum, oxytocin review, oxytocin labor, oxytocin release. The best evidence from the literature based on the methodology they used is included. The word oxytocin comes from the Greek words omega Chi upsilon xi, tau omicron Chi omicron chi xi, which means "swift birth". It is synthesized in the paraventricular and supraoptic nuclei of the hypotalamus is mainly released from the neurohypophysis and nerve terminals. It travels from the brain to the heart and the whole body, activating or modulating a wide range of functions and emotions. Mainly cause myometrial contractions and myoepithelial cells of the breast for milk ejection. Its adverse effects are dose-related. No one knows exactly the minumum and maximum dose of oxytocin. More research is needed about central and peripheral receptors, coupled with the use to which they currently gives to agonists and antagonists of oxytocin and its receptor. As of 2013, the documented adverse effects to date have been undervalued.

Carbetocin versus oxytocin for prevention of post-partum haemorrhage at caesarean section in the United Kingdom: An economic impact analysis.

PubMed

van der Nelson, Helen A; Draycott, Tim; Siassakos, Dimitrios; Yau, Christopher W H; Hatswell, Anthony J

2017-03-01

To determine the economic impact of the introduction of carbetocin for the prevention of postpartum haemorrhage (PPH) at caesarean section, compared to oxytocin. The model is a decision tree conducted from a UK National Health Service perspective. 1500 caesarean sections (both elective and emergency) were modelled over a 12 month period. Efficacy data was taken from a published Cochrane meta-analysis, and costs from NHS Reference costs, the British National Formulary and the NHS electronic Medicines Information Tool. A combination of hospital audit data and expert input from an advisory board of clinicians was used to inform resource use estimates. The main outcome measures were the incidence of PPH and total cost over a one year time horizon, as a result of using carbetocin compared to oxytocin for prevention of PPH at caesarean section. The use of carbetocin compared to oxytocin for prevention of PPH at caesarean section was associated with a reduction of 30 (88 vs 58) PPH events (>500ml blood loss), and a cost saving of £27,518. In probabilistic sensitivity analysis, carbetocin had a 91.5% probability of producing better outcomes, and a 69.4% chance of being dominant (both cheaper and more effective) compared to oxytocin. At list price, the introduction of carbetocin appears to provide improved clinical outcomes along with cost savings, though this is subject to uncertainty regarding the underlying data in efficacy, resource use, and cost. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Oxytocin Indexes Relational Distress Following Interpersonal Harms in Women

PubMed Central

Tabak, Benjamin A.; McCullough, Michael E.; Szeto, Angela; Mendez, Armando J.; McCabe, Philip M.

2010-01-01

Summary The hypothalamic neuropeptide oxytocin, known for its involvement in social affiliation and bonding in animals, has recently been associated with a host of prosocial behaviors that are beneficial for maintaining positive social relationships in humans. Paradoxically, however, people with high endogenous levels of oxytocin also tend to report relational distress and interpersonal difficulties in their everyday lives. To address these contradictory findings, oxytocin reactivity was measured in response to a well-defined laboratory task in young adult women following recent interpersonal harms. Elevated mean peripheral oxytocin reactivity (but not baseline levels of oxytocin or cortisol reactivity) was associated with increased post-conflict anxiety and decreased levels of forgiveness. These results corroborate previous research implicating oxytocin as a neuroendocrine marker of relational distress, but not general stress, and demonstrate the utility of studying oxytocin in response to naturally occurring relational events. PMID:20688437

Oxytocin and the Neural Mechanisms Regulating Social Cognition and Affiliative Behavior

PubMed Central

Ross, Heather E.; Young, Larry J.

2009-01-01

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 prosocial interactions, and discuss the neuroanatomy of the central oxytocin system. PMID:19481567

Oxytocin Treatment, Circuitry, and Autism: A Critical Review of the Literature Placing Oxytocin Into the Autism Context.

PubMed

Guastella, Adam J; Hickie, Ian B

2016-02-01

Observed impairment in reciprocal social interaction is a diagnostic hallmark of autism spectrum disorders. There is no effective medical treatment for these problems. Psychological treatments remain costly, time intensive, and developmentally sensitive for efficacy. In this review, we explore the potential of oxytocin-based therapies for social impairments in autism. Evidence shows that acute oxytocin administration improves numerous markers critical to the social circuitry underlying social deficits in autism. Oxytocin may optimize these circuits and enhance reward, motivation, and learning to improve therapeutic outcomes. Despite this, the current evidence of therapeutic benefit from extended oxytocin treatment remains very limited. We highlight complexity in crossing from the laboratory to the autism clinical setting in evaluation of this therapeutic. We discuss a clinical trial approach that provides optimal opportunity for therapeutic response by using personalized methods that better target specific circuitry to define who will obtain benefit, at what stage of development, and the optimal delivery approach for circuitry manipulation. For the autism field, the therapeutic challenges will be resolved by a range of treatment strategies, including greater focus on specific interventions, such as oxytocin, that have a strong basis in the fundamental neurobiology of social behavior. More sophisticated and targeted clinical trials utilizing such approaches are now required, placing oxytocin into the autism context. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Antiaggressive activity of central oxytocin in male rats.

PubMed

Calcagnoli, Federica; de Boer, Sietse F; Althaus, Monika; den Boer, Johan A; Koolhaas, Jaap M

2013-10-01

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 putative serenic effect of oxytocin in a feral strain (wild type Groningen, WTG) of rats that generally show a much broader variation and higher levels of intermale aggression than commonly used laboratory strains of rats. Resident animals were intracerebroventricularly (icv) administered with different doses of synthetic oxytocin and oxytocin receptor antagonist, alone and in combination, in order to manipulate brain oxytocin functioning and to assess their behavioral response to an intruder. Our data clearly demonstrate that acute icv administered oxytocin produces dose-dependent and receptor-selective changes in social behavior, reducing aggression and potentiating social exploration. These antiaggressive effects are stronger in the more offensive rats. On the other hand, administration of an oxytocin receptor antagonist tends to increase (nonsignificantly) aggression only in low-medium aggressive animals. These results suggest that transiently enhancing brain oxytocin function has potent antiaggressive effects, whereas its attenuation tends to enhance aggressiveness. In addition, a possible inverse relationship between trait aggression and endogenous oxytocinergic signaling is revealed. Overall, this study emphasizes the importance of brain oxytocinergic signaling for regulating intermale offensive aggression. This study supports the suggestion that oxytocin receptor agonists could clinically be useful for curbing heightened aggression seen in a range of neuropsychiatric disorders like antisocial personality disorder, autism, and addiction.

Maternal Oxytocin Response Predicts Mother-to-Infant Gaze

PubMed Central

Kim, Sohye; Fonagy, Peter; Koos, Orsolya; Dorsett, Kimberly; Strathearn, Lane

2014-01-01

The neuropeptide oxytocin is importantly implicated in the emergence and maintenance of maternal behavior that forms the basis of the mother-infant bond. However, no research has yet examined the specific association between maternal oxytocin and maternal gaze, a key modality through which the mother makes social contact and engages with her infant. Furthermore, prior oxytocin studies have assessed maternal engagement primarily during episodes free of infant distress, while maternal engagement during infant distress is considered to be uniquely relevant to the formation of secure mother-infant attachment. Two patterns of maternal gaze, maternal gaze toward and gaze shifts away from the infant, were micro-coded while 50 mothers interacted with their 7-month-old infants during a modified still-face procedure. Maternal oxytocin response was defined as a change in the mother’s plasma oxytocin level following interaction with her infant as compared to baseline. The mother’s oxytocin response was positively associated with the duration of time her gaze was directed toward her infant, while negatively associated with the frequency with which her gaze shifted away from her infant. Importantly, mothers who showed low/average oxytocin response demonstrated a significant decrease in their gaze toward their infants during periods of infant distress, while such change was not observed in mothers with high oxytocin response. The findings underscore the involvement of oxytocin in regulating the mother’s responsive engagement with her infant, particularly in times when the infant’s need for access to the mother is greatest. PMID:24184574

Oxytocin modulation of neural circuits for social behavior.

PubMed

Marlin, Bianca J; Froemke, Robert C

2017-02-01

Oxytocin is a hypothalamic neuropeptide that has gained attention for the effects on social behavior. Recent findings shed new light on the mechanisms of oxytocin in synaptic plasticity and adaptively modifying neural circuits for social interactions such as conspecific recognition, pair bonding, and maternal care. Here, we review several of these newer studies on oxytocin in the context of previous findings, with an emphasis on social behavior and circuit plasticity in various brain regions shown to be enriched for oxytocin receptors. We provide a framework that highlights current circuit-level mechanisms underlying the widespread action of oxytocin. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 169-189, 2017. © 2016 Wiley Periodicals, Inc.

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

ERIC Educational Resources Information Center

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…

Oxytocin mediated behavior in invertebrates: An evolutionary perspective.

PubMed

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.

Oxytocin in survivors of childhood-onset craniopharyngioma.

PubMed

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).

Oxytocin modulates hemodynamic responses to monetary incentives in humans

PubMed Central

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

Lack of Association between Human Plasma Oxytocin and Interpersonal Trust in a Prisoner’s Dilemma Paradigm

PubMed Central

Christensen, James C.; Shiyanov, Pavel A.; Estepp, Justin R.; Schlager, John J.

2014-01-01

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. PMID:25549255

Intranasal administration of oxytocin increases human aggressive behavior.

PubMed

Ne'eman, R; Perach-Barzilay, N; Fischer-Shofty, M; Atias, A; Shamay-Tsoory, S G

2016-04-01

Considering its role in prosocial behaviors, oxytocin (OT) has been suggested to diminish levels of aggression. Nevertheless, recent findings indicate that oxytocin may have a broader influence on increasing the salience of social stimuli and may therefore, under certain circumstances, increase antisocial behaviors such as aggression. This controversy led to the following speculations: If indeed oxytocin promotes primarily prosocial behavior, administration of OT is expected to diminish levels of aggression. However, if oxytocin mainly acts to increase the salience of social stimuli, it is expected to elevate levels of aggression following provocation. In order to test this assumption we used the Social Orientation Paradigm (SOP), a monetary game played against a fictitious partner that allows measuring three types of responses in the context of provocation: an aggressive response - reducing a point from the fictitious partner, an individualistic response - adding a point to oneself, and a collaborative response - adding half a point to the partner and half a point to oneself. In the current double-blind, placebo-controlled, within-subject study design, 45 participants completed the SOP task following the administration of oxytocin or placebo. The results indicated that among subjects naïve to the procedure oxytocin increased aggressive responses in comparison with placebo. These results support the saliency hypothesis of oxytocin and suggest that oxytocin plays a complex role in the modulation of human behavior. Copyright © 2016 Elsevier Inc. All rights reserved.

Basal salivary oxytocin level predicts extra- but not intra-personal dimensions of emotional intelligence.

PubMed

Koven, Nancy S; Max, Laura K

2014-06-01

A wealth of literature suggests that oxytocin is an important mediator of social cognition, but much of the research to date has relied on pharmaceutical administration methods that can raise oxytocin to artificially high levels. The present study builds upon previous work by examining whether basal oxytocin level predicts intra- and extra-personal (i.e., self- and other-focused) elements of emotional intelligence (EI), independent of shared variance with current mood. The sample included 71 healthy young adults (46 women). Assessment measures included the Mayer-Salovey-Caruso Emotional Intelligence Test Version 2.0 (MSCEIT), the Trait Meta-Mood Scale, and the Profile of Mood States. Peripheral oxytocin levels were examined with enzyme-linked immunosorbent assay from saliva after solid phase extraction. Oxytocin level was unrelated to TMMS scores but was positively associated with performance in the Experiential EI domain of the MSCEIT. However, total mood disturbance was positively related to MSCEIT scores. Hierarchical regression analysis indicated that oxytocin level added unique variance to the prediction of MSCEIT performance beyond that of current mood. These results confirm an association between endogenous levels of oxytocin in healthy adults and a subset of EI abilities, including extra-personal emotion recognition and the channeling of emotions to enhance social proficiency. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effects of oxytocin on social reward learning in humans.

PubMed

Clark-Elford, Rebecca; Nathan, Pradeep J; Auyeung, Bonnie; Voon, Valerie; Sule, Akeem; Müller, Ulrich; Dudas, Robert; Sahakian, Barbara J; Phan, K Luan; Baron-Cohen, Simon

2014-02-01

It has been hypothesised that the mechanisms modulating social affiliation are regulated by reward circuitry. Oxytocin, previously shown to support affiliative behaviour and the processing of socio-emotional stimuli, is expressed in areas of the brain involved in reward and motivation. However, limited data are available that test if oxytocin is directly involved in reward learning, or whether oxytocin can modulate the effect of emotion on reward learning. In a double-blind, randomised, placebo-controlled, within-group study design, 24 typical male volunteers were administered 24 IU of oxytocin or placebo and subsequently completed an affective reward learning task. Oxytocin selectively reduced performance of learning rewards, but not losses, from happy faces. The mechanism by which oxytocin may be exerting this effect is discussed in terms of whether oxytocin is affecting identity recognition via affecting the salience of happy faces. We conclude that oxytocin detrimentally affects learning rewards from happy faces in certain contexts.

Intravenous oxytocin alone for cervical ripening and induction of labour

PubMed Central

Alfirevic, Zarko; Kelly, Anthony J; Dowswell, Therese

2014-01-01

Background Oxytocin is the commonest induction agent used worldwide. It has been used alone, in combination with amniotomy or following cervical ripening with other pharmacological or non-pharmacological methods. Objectives To determine the effects of oxytocin alone for third trimester cervical ripening and induction of labour in comparison with other methods of induction of labour or placebo/no treatment. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (January 2009) and bibliographies of relevant papers. Selection criteria Randomised and quasi-randomised trials comparing intravenous oxytocin with placebo or no treatment, or with prostaglandins (vaginal or intracervical) for third trimester cervical ripening or labour induction. Data collection and analysis Two review authors independently assessed eligibility and carried out data extraction. Main results Sixty-one trials (12,819 women) are included. When oxytocin inductions were compared with expectant management, fewer women failed to deliver vaginally within 24 hours (8.4% versus 53.8%, risk ratio (RR) 0.16, 95% confidence interval (CI) 0.10 to 0.25). There was a significant increase in the number of women requiring epidural analgesia (RR 1.10, 95% CI 1.04 to 1.17). Fewer women were dissatisfied with oxytocin induction in the one trial reporting this outcome (5.9% versus 13.7%, RR 0.43, 95% CI 0.33 to 0.56). Compared with vaginal prostaglandins, oxytocin increased unsuccessful vaginal delivery within 24 hours in the two trials reporting this outcome (70% versus 21%, RR 3.33, 95% CI 1.61 to 6.89). There was a small increase in epidurals when oxytocin alone was used (RR 1.09, 95% CI 1.01 to 1.17). Most of the studies included women with ruptured membranes, and there was some evidence that vaginal prostaglandin increased infection in mothers (chorioamnionitis RR 0.66, 95% CI 0.47 to 0.92) and babies (use of antibiotics RR 0.68, 95% CI 0.53 to 0.87). These data should be

Sex differences in methamphetamine seeking in rats: Impact of oxytocin

PubMed Central

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 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 1 mg/kg, IP) 30 min before a meth priming injection (1 mg/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

Oxytocin modulates human communication by enhancing cognitive exploration.

PubMed

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.

Oxytocin modulates GABAAR subunits to confer neuroprotection in stroke in vitro.

PubMed

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.

Oxytocin: its role in benign prostatic hyperplasia via the ERK pathway.

PubMed

Xu, Huan; Fu, Shi; Chen, Yanbo; Chen, Qi; Gu, Meng; Liu, Chong; Qiao, Zhiguang; Zhou, Juan; Wang, Zhong

2017-04-01

The aim of the present study was to evaluate oxytocin and benign prostatic hyperplasia (BPH), and study the cell signalling mechanism. Investigation was performed in patients about the correlation between oxytocin level and BPH. Mice were injected with oxytocin or oxytocin antagonist for 2 weeks and the prostate morphology was studied after their sacrifice. Furthermore, in vitro experiments were performed to evaluate the oxytocin effect through the MEK/ERK/RSK pathway. Oxytocin was significantly elevated in the serum and prostate tissue of patients with BPH, and a positive correlation with prostate volume indicated. In the animal experiments, prostate enlargement was observed in the oxytocin-treated group, whereas oxytocin antagonist reduced prostate hyperplasia. The in vitro study confirmed this result and also revealed activation of the MEK/ERK/RSK pathway. Oxytocin is highly expressed in the serum and prostate tissue of patients with BPH. In addition, oxytocin aggravates BPH and the oxytocin-induced proliferative effect on prostatic cells is mediated through the MEK/ERK/RSK pathway, at least partly. Thus, the hypothalamic regulation may be involved in development of BPH, which may open a new door to more medications for BPH in the future. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Effects of N-acetylimidazole on oxytocin binding in bovine mammary tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, X.; Gorewit, R.C.; Currie, W.B.

1990-01-01

The effects of N-acetylimidazole on specific binding of oxytocin to microsomal fractions of bovine mammary gland were studied. N-acetylimidazole suppressed oxytocin binding, with time and concentration dependence. Decreased oxytocin binding activity appeared to be due to decreased affinity of the hormone for its receptor. Acetylation of oxytocin, rather than of oxytocin receptors, seemed to be responsible for the decreased binding.

Oxytocin eliminates the own-race bias in face recognition memory.

PubMed

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.

Increased Serum and Urinary Oxytocin Concentrations after Nasal Administration in Beagle Dogs

PubMed Central

Temesi, Andrea; Thuróczy, Julianna; Balogh, Lajos; Miklósi, Ádám

2017-01-01

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. PMID:28929104

Prolactin regulation of oxytocin neurone activity in pregnancy and lactation.

PubMed

Augustine, Rachael A; Ladyman, Sharon R; Bouwer, Gregory T; Alyousif, Yousif; Sapsford, Tony J; Scott, Victoria; Kokay, Ilona C; Grattan, David R; Brown, Colin H

2017-06-01

During lactation, prolactin promotes milk synthesis and oxytocin stimulates milk ejection. In virgin rats, prolactin inhibits the activity of oxytocin-secreting neurones. We found that prolactin inhibition of oxytocin neurone activity is lost in lactation, and that some oxytocin neurones were excited by prolactin in lactating rats. The change in prolactin regulation of oxytocin neurone activity was not associated with a change in activation of intracellular signalling pathways known to couple to prolactin receptors. The change in prolactin regulation of oxytocin neurone activity in lactation might allow coordinated activation of both populations of neurones when required for successful lactation. Secretion of prolactin for milk synthesis and oxytocin for milk secretion is required for successful lactation. In virgin rats, prolactin inhibits oxytocin neurones but this effect would be counterproductive during lactation when secretion of both hormones is required for synthesis and delivery of milk to the newborn. Hence, we determined the effects of intracerebroventricular (i.c.v.) prolactin on oxytocin neurones in urethane-anaesthetised virgin, pregnant and lactating rats. Prolactin (2 μg) consistently inhibited oxytocin neurones in virgin and pregnant rats (by 1.9 ± 0.4 and 1.8 ± 0.5 spikes s -1 , respectively), but not in lactating rats; indeed, prolactin excited six of 27 oxytocin neurones by >1 spike s -1 in lactating rats but excited none in virgin or pregnant rats (χ 2 2  = 7.2, P = 0.03). Vasopressin neurones were unaffected by prolactin (2 μg) in virgin rats but were inhibited by 1.1 ± 0.2 spikes s -1 in lactating rats. Immunohistochemistry showed that i.c.v. prolactin increased oxytocin expression in virgin and lactating rats and increased signal transducer and activator of transcription 5 phosphorylation to a similar extent in oxytocin neurones of virgin and lactating rats. Western blotting showed that i.c.v. prolactin did not affect

Oxytocin, testosterone, and human social cognition.

PubMed

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

Oxytocin reduces alcohol consumption in prairie voles.

PubMed

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.

Gender differences in oxytocin-associated disruption of decision bias during emotion perception.

PubMed

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.

Implementation of an Oxytocin Checklist to Improve Clinical Outcomes.

PubMed

Sundin, Courtney; Mazac, Lauren; Ellis, Kathleen; Garbo, Candon

Oxytocin is one of the most common drugs administered in obstetrics. Since its designation as a high-alert medication by the Institute for Safe Medication Practices in 2007, there has been much attention to oxytocin administration during labor. Oxytocin is generally safe when administered correctly, but adverse perinatal outcomes can occur during uterine tachysystole. The purpose of this project was to evaluate and compare results of maternal and fetal outcomes of induction of labor for women at term prior to and after implementation of a newly developed oxytocin checklist. To evaluate the practice change associated with the implementation of the new oxytocin checklist, 200 cases based on retrospective medical record reviews were compared with 200 cases after implementation. Use of the checklist was associated with several significant clinical outcomes, including decreases in tachysystole, decreases in cesarean births for concern about fetal status based on electronic fetal monitoring data, decreases in length of first stage labor, and decreases in maximum dose of oxytocin. Results are similar to previous research. Early physician buy-in, clinical team education, and ongoing evaluation enhanced facilitation of the oxytocin checklist. Clinical outcomes were favorable.

Enhancing Placebo Effects in Somatic Symptoms Through Oxytocin.

PubMed

Skvortsova, Aleksandrina; Veldhuijzen, Dieuwke S; Van Middendorp, Henriët; Van den Bergh, Omer; Evers, Andrea W M

2018-05-01

Placebo effects relieve various somatic symptoms, but it is unclear how they can be enhanced to maximize positive treatment outcomes. Oxytocin administration may potentially enhance placebo effects, but few studies have been performed, and they have had conflicting findings. The study aim was to investigate the influence of positive verbal suggestions and oxytocin on treatment expectations and placebo effects for pain and itch. One hundred eight female participants were allocated to one of the following four groups: (1) oxytocin with positive verbal suggestions, (2) placebo with positive verbal suggestions, (3) oxytocin without suggestions, and (4) placebo without suggestions. The administration of 24 IU oxytocin or a placebo spray was preceded by positive verbal suggestions regarding the pain- and itch-relieving properties of the spray or no suggestions, depending on group allocation. Pain was assessed with a cold pressor test, and itch was assessed with histamine iontophoresis. Positive verbal suggestions induced expectations of lower pain (F = 4.77, p = .031) and itch (F = 5.38, p = .022). Moreover, positive verbal suggestions elicited placebo analgesia (F = 5.48, p = .021) but did not decrease itch. No effect of oxytocin on the placebo effect or on expectations was found. Positive suggestions induced placebo analgesia but oxytocin did not enhance the placebo effect. Study limitations are that we only included a female sample and a failure to induce placebo effect for itch. Future studies should focus on how oxytocin might influence placebo effects, taken into account the role of sex, dose-dependent effects, and various expectation manipulations. The study was registered as a clinical trial on www.trialregister.nl (number 6376).

Oxytocin eliminates the own-race bias in face recognition memory☆

PubMed Central

Blandón-Gitlin, Iris; Pezdek, Kathy; Saldivar, Sesar; Steelman, Erin

2015-01-01

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. PMID:23872107

Correlation between oxytocin neuronal sensitivity and oxytocin receptor binding: An electrophysiological and autoradiographical study comparing rat and guinea pig hippocampus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raggenbass, M.; Tribollet, E.; Dubois-Dauphin, M.

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 {mu}M. The effect of this compound was postsynaptic and was blocked by themore » 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.« less

Oxytocin enhances pupil dilation and sensitivity to 'hidden' emotional expressions.

PubMed

Leknes, Siri; Wessberg, Johan; Ellingsen, Dan-Mikael; Chelnokova, Olga; Olausson, Håkan; Laeng, Bruno

2013-10-01

Sensing others' emotions through subtle facial expressions is a highly important social skill. We investigated the effects of intranasal oxytocin treatment on the evaluation of explicit and 'hidden' emotional expressions and related the results to individual differences in sensitivity to others' subtle expressions of anger and happiness. Forty healthy volunteers participated in this double-blind, placebo-controlled crossover study, which shows that a single dose of intranasal oxytocin (40 IU) enhanced or 'sharpened' evaluative processing of others' positive and negative facial expression for both explicit and hidden emotional information. Our results point to mechanisms that could underpin oxytocin's prosocial effects in humans. Importantly, individual differences in baseline emotional sensitivity predicted oxytocin's effects on the ability to sense differences between faces with hidden emotional information. Participants with low emotional sensitivity showed greater oxytocin-induced improvement. These participants also showed larger task-related pupil dilation, suggesting that they also allocated the most attentional resources to the task. Overall, oxytocin treatment enhanced stimulus-induced pupil dilation, consistent with oxytocin enhancement of attention towards socially relevant stimuli. Since pupil dilation can be associated with increased attractiveness and approach behaviour, this effect could also represent a mechanism by which oxytocin increases human affiliation.

Intranasal oxytocin and a polymorphism in the oxytocin receptor gene are associated with human-directed social behavior in golden retriever dogs.

PubMed

Persson, Mia E; Trottier, Agaia J; Bélteky, Johan; Roth, Lina S V; Jensen, Per

2017-09-01

The oxytocin system may play an important role in dog domestication from the wolf. Dogs have evolved unique human analogue social skills enabling them to communicate and cooperate efficiently with people. Genomic differences in the region surrounding the oxytocin receptor (OXTR) gene have previously been associated with variation in dogs' communicative skills. Here we have utilized the unsolvable problem paradigm to investigate the effects of oxytocin and OXTR polymorphisms on human-directed contact seeking behavior in 60 golden retriever dogs. Human-oriented behavior was quantified employing a previously defined unsolvable problem paradigm. Behaviors were tested twice in a repeated, counterbalanced design, where dogs received a nasal dose of either oxytocin or saline 45min before each test occasion. Buccal DNA was analysed for genotype on three previously identified SNP-markers associated with OXTR. The same polymorphisms were also genotyped in 21 wolf blood samples to explore potential genomic differences between the species. Results showed that oxytocin treatment decreased physical contact seeking with the experimenter and one of the three polymorphisms was associated with degree of physical contact seeking with the owner. Dogs with the AA-genotype at this locus increased owner physical contact seeking in response to oxytocin while the opposite effect was found in GG-genotype individuals. Hence, intranasal oxytocin treatment, an OXTR polymorphism and their interaction are associated with dogs' human-directed social skills, which can explain previously described breed differences in oxytocin response. Genotypic variation at the studied locus was also found in wolves indicating that it was present even at the start of dog domestication. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison effect of oral propranolol and oxytocin versus oxytocin only on induction of labour in nulliparous women (a double blind randomized trial).

PubMed

Moghadam, Ashraf Direkvand; Jaafarpour, Molouk; Khani, Ali

2013-11-01

Today, research on new methods for preventing caesarean sections owing to labour induction, have been requested in obstetric practice, because of the increased morbidity related to caesarean section. Therefore, the aim of this study was to compare the effect of Oral Propranolol and Oxytocin versus Oxytocin only on induction of labour in nulliparous women. A double blind randomized controlled trial was performed at the Ilam Mostafa Hospital, Ilam, Iran, from March 2010 to March 2011 on 146 nulliparous pregnant women who had gestational age of 40-42 weeks of pregnancy and a Bishop score of ≤5. Participants were divided in two groups (with 73 participants in each group). In the first group (placebo plus Oxytocin group = 73), Oxytocin was used for the induction of labour. In the second group (Propranolol plus Oxytocin group = 73 cases), before the use of Oxytocin, 20 mg Propranolol was administrated orally and then the Oxytocin was initiated. Twenty mg Propranolol was repeated after 8 hours if good contraction was not obtained. The mean duration for obtaining good contractions was significantly shorter in the Propranolol group than in the placebo group, on both the first and second day of induction (p<.05). The mean duration of latent phase was shorter in the first in Propranolol group (p<.05). In Propranolol plus Oxytocine group, frequency of cesarean deliveries significantly decreased than in the placebo plus Oxytocin group (21% versus 39.7%). No significant differences in neonate outcome, such as Apgar scores of minutes 1 and 5 and need of admissions to NICU, were found between the groups (p>.05) DISCUSSION AND CONCLUSION: Our study showed that oral Propranolol was effective for labour induction and that it could decrease the frequency of caesarean deliveries without producing any adverse effects on mothers or neonates.

Human Neuroimaging of Oxytocin and Vasopressin in Social Cognition

PubMed Central

Zink, Caroline F; Meyer-Lindenberg, Andreas

2012-01-01

The neuropeptides oxytocin and vasopressin have increasingly been identified as modulators of human social behaviors and associated with neuropsychiatric disorders characterized by social dysfunction, such as autism. Identifying the human brain regions that are impacted by oxytocin and vasopressin in a social context is essential to fully characterize the role of oxytocin and vasopressin in complex human social cognition. Advances in human non-invasive neuroimaging techniques and genetics have enabled scientists to begin to elucidate the neurobiological basis of the influence of oxytocin and vasopressin on human social behaviors. Here we review the findings to-date from investigations of the acute and chronic effects of oxytocin and vasopressin on neural activity underlying social cognitive processes using “pharmacological fMRI” and “imaging genetics”, respectively. PMID:22326707

Oxytocin, Motivation and the Role of Dopamine

PubMed Central

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

Endocannabinoid signaling mediates oxytocin-driven social reward.

PubMed

Wei, Don; Lee, DaYeon; Cox, Conor D; Karsten, Carley A; Peñagarikano, Olga; Geschwind, Daniel H; Gall, Christine M; Piomelli, Daniele

2015-11-10

Marijuana exerts profound effects on human social behavior, but the neural substrates underlying such effects are unknown. Here we report that social contact increases, whereas isolation decreases, the mobilization of the endogenous marijuana-like neurotransmitter, anandamide, in the mouse nucleus accumbens (NAc), a brain structure that regulates motivated behavior. Pharmacological and genetic experiments show that anandamide mobilization and consequent activation of CB1 cannabinoid receptors are necessary and sufficient to express the rewarding properties of social interactions, assessed using a socially conditioned place preference test. We further show that oxytocin, a neuropeptide that reinforces parental and social bonding, drives anandamide mobilization in the NAc. Pharmacological blockade of oxytocin receptors stops this response, whereas chemogenetic, site-selective activation of oxytocin neurons in the paraventricular nucleus of the hypothalamus stimulates it. Genetic or pharmacological interruption of anandamide degradation offsets the effects of oxytocin receptor blockade on both social place preference and cFos expression in the NAc. The results indicate that anandamide-mediated signaling at CB1 receptors, driven by oxytocin, controls social reward. Deficits in this signaling mechanism may contribute to social impairment in autism spectrum disorders and might offer an avenue to treat these conditions.

Nonclinical dose formulation analysis method validation and sample analysis.

PubMed

Whitmire, Monica Lee; Bryan, Peter; Henry, Teresa R; Holbrook, John; Lehmann, Paul; Mollitor, Thomas; Ohorodnik, Susan; Reed, David; Wietgrefe, Holly D

2010-12-01

Nonclinical dose formulation analysis methods are used to confirm test article concentration and homogeneity in formulations and determine formulation stability in support of regulated nonclinical studies. There is currently no regulatory guidance for nonclinical dose formulation analysis method validation or sample analysis. Regulatory guidance for the validation of analytical procedures has been developed for drug product/formulation testing; however, verification of the formulation concentrations falls under the framework of GLP regulations (not GMP). The only current related regulatory guidance is the bioanalytical guidance for method validation. The fundamental parameters for bioanalysis and formulation analysis validations that overlap include: recovery, accuracy, precision, specificity, selectivity, carryover, sensitivity, and stability. Divergence in bioanalytical and drug product validations typically center around the acceptance criteria used. As the dose formulation samples are not true "unknowns", the concept of quality control samples that cover the entire range of the standard curve serving as the indication for the confidence in the data generated from the "unknown" study samples may not always be necessary. Also, the standard bioanalytical acceptance criteria may not be directly applicable, especially when the determined concentration does not match the target concentration. This paper attempts to reconcile the different practices being performed in the community and to provide recommendations of best practices and proposed acceptance criteria for nonclinical dose formulation method validation and sample analysis.

Nasal Oxytocin Treatment Biases Dogs’ Visual Attention and Emotional Response toward Positive Human Facial Expressions

PubMed Central

Somppi, Sanni; Törnqvist, Heini; Topál, József; Koskela, Aija; Hänninen, Laura; Krause, Christina M.; Vainio, Outi

2017-01-01

The neuropeptide oxytocin plays a critical role in social behavior and emotion regulation in mammals. The aim of this study was to explore how nasal oxytocin administration affects gazing behavior during emotional perception in domestic dogs. Looking patterns of dogs, as a measure of voluntary attention, were recorded during the viewing of human facial expression photographs. The pupil diameters of dogs were also measured as a physiological index of emotional arousal. In a placebo-controlled within-subjects experimental design, 43 dogs, after having received either oxytocin or placebo (saline) nasal spray treatment, were presented with pictures of unfamiliar male human faces displaying either a happy or an angry expression. We found that, depending on the facial expression, the dogs’ gaze patterns were affected selectively by oxytocin treatment. After receiving oxytocin, dogs fixated less often on the eye regions of angry faces and revisited (glanced back at) more often the eye regions of smiling (happy) faces than after the placebo treatment. Furthermore, following the oxytocin treatment dogs fixated and revisited the eyes of happy faces significantly more often than the eyes of angry faces. The analysis of dogs’ pupil diameters during viewing of human facial expressions indicated that oxytocin may also have a modulatory effect on dogs’ emotional arousal. While subjects’ pupil sizes were significantly larger when viewing angry faces than happy faces in the control (placebo treatment) condition, oxytocin treatment not only eliminated this effect but caused an opposite pupil response. Overall, these findings suggest that nasal oxytocin administration selectively changes the allocation of attention and emotional arousal in domestic dogs. Oxytocin has the potential to decrease vigilance toward threatening social stimuli and increase the salience of positive social stimuli thus making eye gaze of friendly human faces more salient for dogs. Our study provides

Oxytocin conditions trait-based rule adherence.

PubMed

Gross, Jörg; De Dreu, Carsten K W

2017-03-01

Rules, whether in the form of norms, taboos or laws, regulate and coordinate human life. Some rules, however, are arbitrary and adhering to them can be personally costly. Rigidly sticking to such rules can be considered maladaptive. Here, we test whether, at the neurobiological level, (mal)adaptive rule adherence is reduced by oxytocin-a hypothalamic neuropeptide that biases the biobehavioural approach-avoidance system. Participants (N = 139) self-administered oxytocin or placebo intranasally, and reported their need for structure and approach-avoidance sensitivity. Next, participants made binary decisions and were given an arbitrary rule that demanded to forgo financial benefits. Under oxytocin, participants violated the rule more often, especially when they had high need for structure and high approach sensitivity. Possibly, oxytocin dampens the need for a highly structured environment and enables individuals to flexibly trade-off internal desires against external restrictions. Implications for the treatment of clinical disorders marked by maladaptive rule adherence are discussed. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Oxytocin Intranasal Administration Affects Neural Networks Upstream of GNRH Neurons.

PubMed

Salehi, Mohammad Saied; Khazali, Homayoun; Mahmoudi, Fariba; Janahmadi, Mahyar

2017-08-01

The last decade has witnessed a surge in studies on the clinical applications of intranasal oxytocin as a method of enhancing social interaction. However, the molecular and cellular mechanisms underlying its function are not completely understood. Since oxytocin is involved in the regulation of hypothalamic-pituitary-gonadal axis by affecting the gonadotropin-releasing hormone (GNRH) system, the present study addressed whether intranasal application of oxytocin has a role in affecting GNRH expression in the male rat hypothalamus. In addition, we assessed expression of two excitatory (kisspeptin and neurokinin B) and two inhibitory (dynorphin and RFamide-related peptide-3) neuropeptides upstream of GNRH neurons as a possible route to relay oxytocin information. Here, adult male rats received 20, 40, or 80 μg oxytocin intranasally once a day for 10 consecutive days, and then, the posterior (PH) and anterior hypothalamus (AH) dissected for evaluation of target genes. Using qRT-PCR, we found that oxytocin treatment increased Gnrh mRNA levels in both the PH and AH. In addition, oxytocin at its highest dose increased kisspeptin expression in the AH by around 400%, whereas treatments, dose dependently decreased kisspeptin mRNA in the PH. The expression of neurokinin B was increased from the basal levels following the intervention. Furthermore, although intranasal-applied oxytocin decreased hypothalamic RFamide-related peptide-3 mRNA level, the dynorphin mRNA was not affected. These observations are consistent with the hypothesis that applications of intranasal oxytocin can affect the GNRH system.

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

PubMed Central

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

A review of clinical trials of oxytocin in Prader-Willi syndrome.

PubMed

Rice, Lauren J; Einfeld, Stewart L; Hu, Nan; Carter, C Sue

2018-03-01

PWS is a severe developmental disability for which there is no known treatment. The oxytocin system is currently a primary target for intervention. The aim of this article is to review the evidence for the efficacy of intranasal oxytocin in PWS. To date, there have been five clinical trials of oxytocin in PWS. Four of these studies reported that oxytocin improved behaviors. However, each of these studies suffered important limitations that likely influenced the findings. For example, one study did not include a control group. Another study did not statistically analyze the effects of oxytocin on behavior. The final two studies used study-specific measures for which psychometric properties have not been assessed. Because of these limitations, the most appropriate conclusion to draw from the existing studies is that there is currently no convincing evidence that intranasal oxytocin improves symptoms of PWS. However, this does not mean that oxytocin is not involved in PWS. Rather, it suggests that further work is needed to understand the nature of the PWS oxytocin abnormality.

Oxytocin differently regulates pressor responses to stress in WKY and SHR rats: the role of central oxytocin and V1a receptors.

PubMed

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.

Hypothalamic oxytocin mediates social buffering of the stress response

PubMed Central

Smith, Adam S.; Wang, Zuoxin

2013-01-01

Background 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. Methods Female prairie voles (Microtus ochrogaster) were exposed to 1 hr immobilization stress 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 females recovering alone with oxytocin, or vehicle, and females recovering with their male partner with a selective oxytocin receptor antagonist, or vehicle. Group sizes varied from 6 to 8 voles (n = 98 total). Results We found that 1 hr immobilization increased anxiety-like behaviors and circulating levels of corticosterone, a stress hormone, in females recovering alone, but not the females 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 (PVN) of the hypothalamus. Intra-PVN oxytocin injections reduced behavioral and corticosterone responses to immobilization whereas injections of an oxytocin receptor antagonist blocked the effects of the social buffering. Conclusions Together, our data demonstrate that PVN oxytocin mediates the social buffering effects on the stress response, and thus may be a target for treatment of stress-related disorders. PMID:24183103

Titration of Intravenous Oxytocin Infusion for Postdates Induction of Labor Across Body Mass Index Groups.

PubMed

Maeder, Angela B; Vonderheid, Susan C; Park, Chang G; Bell, Aleeca F; McFarlin, Barbara L; Vincent, Catherine; Carter, C Sue

To evaluate whether oxytocin titration for postdates labor induction differs among women who are normal weight, overweight, and obese and whether length of labor and birth method differ by oxytocin titration and body mass index (BMI). Retrospective cohort study. U.S. university-affiliated hospital. Of 280 eligible women, 21 were normal weight, 134 were overweight, and 125 were obese at labor admission. Data on women who received oxytocin for postdates induction between January 1, 2013 and June 30, 2013 were extracted from medical records. Oxytocin administration and labor outcomes were compared across BMI groups, controlling for potential confounders. Data were analyzed using χ 2 , analysis of variance, analysis of covariance, and multiple linear and logistic regression models. Women who were obese received more oxytocin than women who were overweight in the unadjusted analysis of variance (7.50 units compared with 5.92 units, p = .031). Women who were overweight had more minutes between rate changes from initiation to maximum than women who were obese (98.19 minutes compared with 83.39 minutes, p = .038). Length of labor increased with BMI (p = .018), with a mean length of labor for the normal weight group of 13.96 hours (standard deviation = 8.10); for the overweight group, 16.00 hours (standard deviation = 7.54); and for the obese group, 18.30 hours (standard deviation = 8.65). Cesarean rate increased with BMI (p = .001), with 4.8% of normal weight, 33.6% of overweight, and 42.4% of obese women having cesarean births. Women who were obese and experienced postdates labor induction received more oxytocin than women who were non-obese and had longer length of labor and greater cesarean rates. Copyright © 2017 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.

Is Oxytocin Application for Autism Spectrum Disorder Evidence-Based?

PubMed Central

Lee, Seung Yup; Lee, Ah Rah; Hwangbo, Ram; Han, Juhee; Hong, Minha

2015-01-01

Autism spectrum disorder (ASD) is characterized by persistent deficits within two core symptom domains: social communication and restricted, repetitive behaviors. Although numerous studies have reported psychopharmacological treatment outcomes for the core symptom domains of ASD, there are not enough studies on fundamental treatments based on the etiological pathology of ASD. Studies on candidate medications related to the pathogenesis of ASD, such as naltrexone and secretin, were conducted, but the results were inconclusive. Oxytocin has been identified as having an important role in maternal behavior and attachment, and it has been recognized as a key factor in the social developmental deficit seen in ASD. Genetic studies have also identified associations between ASD and the oxytocin pathway. As ASD has its onset in infancy, parents are willing to try even experimental or unapproved treatments in an effort to avoid missing the critical period for diagnosis and treatment, which can place their child in an irreversible state. While therapeutic application of oxytocin for ASD is in its early stages, we have concluded that oxytocin would be a promising therapeutic substance via a thorough literature review focusing on the following: the relationship between oxytocin and sociality; single nucleotide polymorphisms as a biological marker of ASD; and validity verification of oxytocin treatment in humans. We also reviewed materials related to the mechanism of oxytocin action that may support its potential application in treating ASD. PMID:26713079

Oxytocin binding sites in bovine mammary tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Xin.

1989-01-01

Oxytocin binding sites were identified and characterized in bovine mammary tissue. ({sup 3}H)-oxytocin binding reached equilibrium by 50 min at 20{degree}C and by 8 hr at 4{degree}C. The half-time of displacement at 20{degree}C was approximately 1 hr. Thyrotropin releasing hormone, adrenocorticotropin, angiotensin I, angiotensin II, pentagastrin, bradykinin, xenopsin and L-valyl-histidyl-L-leucyl-L-threonyl-L-prolyl-L-valyl-L-glutamyl-L-lysine were not competitive. In the presence of 10 nM LiCl, addition of oxytocin to dispersed bovine mammary cells, in which phosphatidylinositol was pre-labelled, caused a time and dose-dependent increase in radioactive inositiol monophosphate incorporation. The possibility that there are distinct vasopressin receptors in bovine mammary tissue was investigated. ({sup 3}H)-vasopressinmore » binding reached equilibrium by 40 min at 20{degree}. The half-time of displacement at 20{degree}C was approximately 1 hr. The ability of the peptides to inhibit ({sup 3}H)-vasopressin binding was: (Thr{sup 4},Gly{sup 7})-oxytocin > Arg{sup 8}-vasopressin > (lys{sup 8})-vasopressin > (Deamino{sup 1},D-arg{sup 8})-vasopressin > oxytocin > d (CH{sub 2}){sub 5}Tyr(Me)AVP.« less

Elevated plasma oxytocin levels in children with Prader-Willi syndrome compared with healthy unrelated siblings.

PubMed

Johnson, Lisa; Manzardo, Ann M; Miller, Jennifer L; Driscoll, Daniel J; Butler, Merlin G

2016-03-01

Prader-Willi syndrome (PWS) is a rare genetic disorder associated with distinct abnormal behaviors including hyperphagia, profound social deficits, and obsessive-compulsive tendencies. PWS males showed reduced oxytocin receptor (OTR) gene expression and density in the hypothalamic paraventricular nucleus that may play a role in PWS psychopathology. Oxytocin is an anorexigenic neuropeptide similar to vasopressin that is associated with social cognition and obsessive-compulsive behavior. To evaluate oxytocin biology in PWS, we examined overnight fasting plasma oxytocin levels in 23 children with PWS (mean ± SD age: 8.2 ± 2.0 year) having genetic confirmation and 18 age matched healthy unrelated siblings without PWS (mean ± SD age: 8.2 ± 2.3 year) and a similar gender ratio under the same clinical assessments, specimen processing and laboratory conditions. Multiplex immune assays were carried out using the Milliplex Human Neuropeptide Magnetic panel and the Luminex system. Natural log-transformed oxytocin levels were analyzed using general linear model adjusting for diagnosis, gender, age and body mass index (BMI). Oxytocin plasma levels were significantly elevated in children with PWS (168 ± 121 pg/ml) compared with unrelated and unaffected siblings without the diagnosis of PWS (64.8 ± 83.8 pg/ml, F = 8.8, P < 0.01) and the diagnosis of PWS predicted oxytocin level (F = 9.5, P < 0.003) in controlled regression analysis with an overall model fit R(2) = 0.33 (P < 0.01). The symptoms of hyperphagia, anxiety and repetitive behaviors classically seen in PWS may be related to the disruption of oxytocin responsivity or feedback in the hypothalamic paraventricular nucleus possibly influencing vasopressin signaling. Further study is needed to characterize oxytocin function in PWS. © 2015 Wiley Periodicals, Inc.

Hypothalamic oxytocin mediates social buffering of the stress response.

PubMed

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.

Stimuli and consequences of dendritic release of oxytocin within the brain.

PubMed

Neumann, I D

2007-11-01

The brain oxytocin system has served as a distinguished model system in neuroendocrinology to study detailed mechanisms of intracerebral release, in particular of somatodendritic release, and its behavioural and neuroendocrine consequences. It has been shown that oxytocin is released within various brain regions, but evidence for dendritic release is limited to the main sites of oxytocin synthesis, i.e. the hypothalamic SON (supraoptic nucleus) and PVN (paraventricular nucleus). In the present paper, stimuli of dendritic release of oxytocin and the related neuropeptide vasopressin are discussed, including parturition and suckling, i.e. the period of a highly activated brain oxytocin system. Also, exposure to various pharmacological, psychological or physical stressors triggers dendritic oxytocin release, as monitored by intracerebral microdialysis within the SON and PVN during ongoing behavioural testing. So far, dendritic release of the neuropeptide has only been demonstrated within the hypothalamus, but intracerebral oxytocin release has also been found within the central amygdala and the septum in response to various stimuli including stressor exposure. Such a locally released oxytocin modulates physiological and behavioural reproductive functions, emotionality and hormonal stress responses, as it exerts, for example, pro-social, anxiolytic and antistress actions within restricted brain regions. These discoveries make oxytocin a promising neuromodulator of the brain for psychotherapeutic intervention and treatment of numerous psychiatric illnesses, for example, anxiety-related diseases, social phobia, autism and postpartum depression.

Oxytocin and Social Cognition in Affective and Psychotic Disorders

PubMed Central

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

Changes in social functioning and circulating oxytocin and vasopressin following the migration to a new country.

PubMed

Gouin, Jean-Philippe; Pournajafi-Nazarloo, Hossein; Carter, C Sue

2015-02-01

Prior studies have reported associations between plasma oxytocin and vasopressin and markers of social functioning. However, because most human studies have used cross-sectional designs, it is unclear whether plasma oxytocin and vasopressin influences social functioning or whether social functioning modulates the production and peripheral release of these peptides. In order to address this question, we followed individuals who experienced major changes in social functioning subsequent to the migration to a new country. In this study, 59 new international students were recruited shortly after arrival in the host country and reassessed 2 and 5 months later. At each assessment participants provided information on their current social functioning and blood samples for oxytocin and vasopressin analysis. Results indicated that changes in social functioning were not related to changes in plasma oxytocin. Instead, baseline oxytocin predicted changes in social relationship satisfaction, social support, and loneliness over time. In contrast, plasma vasopressin changed as a function of social integration. Baseline vasopressin was not related to changes in social functioning over time. These results emphasize the different roles of plasma oxytocin and vasopressin in responses to changes in social functioning in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

Leachable diphenylguanidine from rubber closures used in pre-filled syringes: A case study to understand solid and solution interactions with oxytocin.

PubMed

Zidan, Ahmed S; Aqueel, Sabir M; Alayoubi, Alaadin; Mohammad, Adil; Zhang, Jinhui; Rahman, Ziyaur; Faustino, Patrick; Lostritto, Richard T; Ashraf, Muhammad

2017-10-30

Leachables derived from multi-component drug-device syringe systems can result in changes to the quality of drug products. Diphenylguanidine (DPG), a leachable released from styrene butadiene rubber syringe plungers, interacts with Oxytocin to form protein-adducts. This study investigated the mechanism and kinetics of this interaction in both solid and solution states through in-vitro tests and spectroscopic methods For solid state interaction, the protein-adducts with DPG were characterized using SEM, XRD, DSC, FTIR, 13 C ss NMR, and dissolution analysis. For solution state interaction, LC-HRMS was used to assess stability of Oxytocin solutions in presence of various concentrations of DPG at 25°C and 40°C for 4 weeks. Moreover, molecular docking analysis was used to identify possible molecular configurations of the interaction.Results were consistent with the formation of a new solid state with distorted surface morphology for oxytocin-DPG adducts, in which the oxytocin carbonyl group(s) and the secondary amine groups of DPG interact. This interaction was also confirmed by molecular docking analysis through hydrogen bonding (2.31Å) and Van der Waal attraction (3.14Å). Moreover, LC-HRMS analysis revealed an increase in Oxytocin stability and suppression of Oxytocin dimerization by DPG. A potential reduction in the rate of Oxytocin dissolution from the formed adducts was indicative of its strong association with DPG. Hence, the leaching potential of DPG from rubber closures and plungers should be monitored and controlled to maintain the quality and stability of the pharmaceutical product. Published by Elsevier B.V.

The effects of oxytocin on social cognition in borderline personality disorder.

PubMed

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

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

PubMed

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.

Oxytocin and eating disorders: a narrative review on emerging findings and perspectives.

PubMed

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.

Oxytocin Modulates Expression of Neuron and Glial Markers in the Rat Hippocampus.

PubMed

Havránek, T; Lešťanová, Z; Mravec, B; Štrbák, V; Bakoš, J; Bačová, Z

2017-01-01

Neuropeptides including oxytocin belong to the group of factors that may play a role in the control of neuronal cell survival, proliferation and differentiation. The aim of the present study was to investigate potential contribution of oxytocin to neuronal differentiation by measuring gene and protein expression of specific neuron and glial markers in the brain. Neonatal and adult oxytocin administration was used to reveal developmental and/or acute effects of oxytocin in Wistar rats. Gene and protein expression of neuron-specific enolase (NSE) in the hippocampus was increased in 21-day and 2-month old rats in response to neonatal oxytocin administration. Neonatal oxytocin treatment induced a significant increase of gene and protein expression of the marker of astrocytes - glial fibrillary acid protein (GFAP). Oxytocin treatment resulted in a decrease of oligodendrocyte marker mRNA - 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) - in 21-day and 2-month old rats, while no change of CD68 mRNA, marker of microglia, was observed. Central oxytocin administration in adult rats induced a significant increase of gene expression of NSE and CNPase. The present study provides the first data revealing the effect of oxytocin on the expression of neuron and glial markers in the brain. It may be suggested that the oxytocin system is involved in the regulation of development of neuronal precursor cells in the brain.

De-masking oxytocin-deficiency in craniopharyngioma and assessing its link with affective function.

PubMed

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

Oxytocin attenuates neural reactivity to masked threat cues from the eyes.

PubMed

Kanat, Manuela; Heinrichs, Markus; Schwarzwald, Ralf; Domes, Gregor

2015-01-01

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 to the eye vs the mouth region. Intranasal oxytocin administration reduced amygdala reactivity to masked emotions when attending to salient facial features, ie, the eyes of angry faces and the mouth of happy faces. In addition, oxytocin decreased neural responses within the fusiform gyrus and brain stem areas, as well as functional coupling between the amygdala and the fusiform gyrus specifically for threat cues from the eyes. Effects of oxytocin on brain activity were not attributable to differences in behavioral performance, as oxytocin had no impact on mere emotion detection. Our results suggest that oxytocin attenuates neural correlates of early arousal by threat signals from the eye region. As reduced threat sensitivity may increase the likelihood of engaging in social interactions, our findings may have important implications for clinical states of social anxiety.

Oxytocin versus no treatment or delayed treatment for slow progress in the first stage of spontaneous labour.

PubMed

Bugg, George J; Siddiqui, Farah; Thornton, Jim G

2013-06-23

of neonatal and maternal outcomes. Use of early oxytocin resulted in a statistically significant reduction in the mean duration in labour of approximately two hours but did not increase the normal delivery rate. There was significant heterogeneity for this analysis and we carried out a random-effects meta-analysis; however, all of the trials are strongly in the same direction so it is reasonable to conclude that this is the true effect. We also performed a random-effects meta-analysis for the four other analyses which showed substantial heterogeneity in the review. For women making slow progress in spontaneous labour, treatment with oxytocin as compared with no treatment or delayed oxytocin treatment did not result in any discernable difference in the number of caesarean sections performed. In addition there were no detectable adverse effects for mother or baby. The use of oxytocin was associated with a reduction in the time to delivery of approximately two hours which might be important to some women. However, if the primary goal of this treatment is to reduce caesarean section rates, then doctors and midwives may have to look for alternative options.

The effects of oxytocin on eating behaviour and metabolism in humans.

PubMed

Lawson, Elizabeth A

2017-12-01

Oxytocin, a hypothalamic hormone that is secreted directly into the brain and enters the peripheral circulation through the posterior pituitary gland, regulates a range of physiologic processes, including eating behaviour and metabolism. In rodents and nonhuman primates, chronic oxytocin administration leads to sustained weight reduction by reducing food intake, increasing energy expenditure and inducing lipolysis. Oxytocin might improve glucose homeostasis, independently of its effects on weight. Clinical studies are beginning to translate these important preclinical findings to humans. This Review describes key data linking oxytocin to eating behaviour and metabolism in humans. For example, a single intranasal dose of oxytocin can reduce caloric intake, increase fat oxidation and improve insulin sensitivity in men. Furthermore, a pilot study of 8 weeks of oxytocin treatment in adults with obesity or overweight led to substantial weight loss. Together, these data support further investigation of interventions that target pathways involving oxytocin as potential therapeutics in metabolic disorders, including obesity and diabetes mellitus. Therapeutic considerations and areas for further research are also discussed.

Oxytocin increases bias, but not accuracy, in face recognition line-ups.

PubMed

Bate, Sarah; Bennetts, Rachel; Parris, Benjamin A; Bindemann, Markus; Udale, Robert; Bussunt, Amanda

2015-07-01

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 test of unfamiliar face recognition containing target-present and target-absent line-ups. Participants in the oxytocin condition outperformed those in the placebo condition on target-present trials, yet were more likely to make false-positive errors on target-absent trials. Signal detection analyses indicated that oxytocin induced a more liberal response bias, rather than increasing accuracy per se. These findings support a social salience account of the effects of oxytocin on face recognition and indicate that oxytocin may impede face recognition in certain scenarios. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Emotion recognition and oxytocin in patients with schizophrenia

PubMed Central

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

Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders.

PubMed

Guastella, Adam J; Einfeld, Stewart L; Gray, Kylie M; Rinehart, Nicole J; Tonge, Bruce J; Lambert, Timothy J; Hickie, Ian B

2010-04-01

A diagnostic hallmark of autism spectrum disorders is a qualitative impairment in social communication and interaction. Deficits in the ability to recognize the emotions of others are believed to contribute to this. There is currently no effective treatment for these problems. In a double-blind, randomized, placebo-controlled, crossover design, we administered oxytocin nasal spray (18 or 24 IU) or a placebo to 16 male youth aged 12 to 19 who were diagnosed with Autistic or Asperger's Disorder. Participants then completed the Reading the Mind in the Eyes Task, a widely used and reliable test of emotion recognition. In comparison with placebo, oxytocin administration improved performance on the Reading the Mind in the Eyes Task. This effect was also shown when analysis was restricted to the younger participants aged 12 to 15 who received the lower dose. This study provides the first evidence that oxytocin nasal spray improves emotion recognition in young people diagnosed with autism spectrum disorders. Findings suggest the potential of earlier intervention and further evaluation of oxytocin nasal spray as a treatment to improve social communication and interaction in young people with autism spectrum disorders. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

The Potential of Nasal Oxytocin Administration for Remediation of Autism Spectrum Disorders

PubMed Central

Okamoto, Yuko; Ishitobi, Makoto; Wada, Yuji; Kosaka, Hirotaka

2016-01-01

Administration of oxytocin has been proposed as a treatment for the core symptoms of autism spectrum disorder (ASD), including social-communicative deficit. Previous clinical trials have investigated the efficacy and safety of oxytocin intranasal single-dose and long-term administration for individuals with ASD. All studies suggest that single-dose and long-term administration are well tolerated, and no severe adverse events have been reported. However, the efficacy of long-term oxytocin administration is controversial. Some studies have reported significant improvement of the core symptoms of ASD by long-term oxytocin administration, while other studies showed no such improvement. To elucidate the factors influencing the efficacy of oxytocin administration, it is necessary to examine the effects of administration schedules (e.g., dosage amount, frequency per day) and participant characteristics (e.g., age, sex, intellectual ability). In addition to doubts about the efficacy of particular methods of administration, questions remain about the mechanism of action of intranasal oxytocin on the central nervous system. Examination of changes in the neural underpinnings of social behavior and simultaneous oxytocin levels in blood or cerebrospinal fluid could prove important in elucidating the pharmacokinetics of intranasal oxytocin administration, which could be essential for establishing optimal oxytocin treatments for individuals with ASD. PMID:27071789

Oxytocin stimulates cell proliferation in vaginal cell line Vk2E6E7.

PubMed

Kallak, Theodora K; Uvnäs-Moberg, Kerstin

2017-03-01

Objective During and after menopause, the symptoms of vaginal atrophy cause great discomfort and necessitate effective treatment options. Currently, vaginally applied oxytocin is being investigated as a treatment for the symptoms of vaginal atrophy in postmenopausal women. To clarify the mechanisms behind oxytocins effects on vaginal atrophy, the present study investigated the effects of oxytocin on cell proliferation in the cells of the Vk2E6E7 line, a non-tumour vaginal cell line. The study also compared the effects of oxytocin with those of estradiol (E2). Study design The effects of both oxytocin and E2 on the proliferation of Vk2E6E7 cells were investigated using Cell Proliferation ELISA BrdU Colorimetric Assay. The expression of both oxytocin and oxytocin receptor was studied in Vk2E6E7 cells using quantitative real-time polymerase chain reaction and immunofluorescent staining. Main outcome measures Cell proliferation and gene expression. Results Oxytocin increased cell proliferation both time dependently and dose dependently. This differed from the effect pattern observed in cells treated with E2. In addition, in oxytocin-treated cells, the oxytocin receptor was found to be co-localized with caveolin-1, indicating pro-proliferative signalling within the cell. Conclusions Oxytocin stimulates cell proliferation and the co-localization of oxytocin receptor with caveolin-1 in oxytocin-treated cells, supporting the role of oxytocin signalling in cell proliferation. In addition, these findings suggest that increased cell proliferation is one mechanism by which local vaginal oxytocin treatment increases vaginal thickness and relieves vaginal symptoms in postmenopausal women with vaginal atrophy.

Neurophysiological effects of acute oxytocin administration: systematic review and meta-analysis of placebo-controlled imaging studies

PubMed Central

Wigton, Rebekah; Radua, Jocham; Allen, Paul; Averbeck, Bruno; Meyer-Lindenberg, Andreas; McGuire, Philip; Shergill, Sukhi S.; Fusar-Poli, Paolo

2015-01-01

Background Oxytocin (OXT) plays a prominent role in social cognition and may have clinical applications for disorders such as autism, schizophrenia and social anxiety. The neural basis of its mechanism of action remains unclear. Methods We conducted a systematic literature review of placebo-controlled imaging studies using OXT as a pharmacological manipulator of brain activity. Results We identified a total of 21 studies for inclusion in our review, and after applying additional selection criteria, 11 of them were included in our fMRI voxel-based meta-analysis. The results demonstrate consistent alterations in activation of brain regions, including the temporal lobes and insula, during the processing of social stimuli, with some variation dependent on sex and task. The meta-analysis revealed significant left insular hyperactivation after OXT administration, suggesting a potential modulation of neural circuits underlying emotional processing. Limitations This quantitative review included only a limited number of studies, thus the conclusions of our analysis should be interpreted cautiously. This limited sample size precluded a more detailed exploration of potential confounding factors, such as sex or other demographic factors, that may have affected our meta-analysis. Conclusion Oxytocin has a wide range of effects over neural activity in response to social and emotional processing, which is further modulated by sex and task specificity. The magnitude of this neural activation is largest in the temporal lobes, and a meta-analysis across all tasks and both sexes showed that the left insula demonstrated the most robust activation to OXT administration. PMID:25520163

Involvement of salsolinol in the suckling-induced oxytocin surge in sheep.

PubMed

Górski, K; Misztal, T; Marciniak, E; Zielińska-Górska, M K; Fülöp, F; Romanowicz, K

2017-04-01

During lactation, the main surge of oxytocin is induced by a suckling stimulus. Previous studies have shown that salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline), a dopamine-derived compound, stimulates both the synthesis and the release of oxytocin in lactating sheep. The objective of the present study was to verify the hypothesis that salsolinol is involved in the mechanism that generates the oxytocin surge that occurs during suckling. Thus, a structural analogue of salsolinol, 1-methyl-3,4-dihydroisoquinoline (1MeDIQ), known to antagonize some of its actions, was infused into the third ventricle of the brain of lactating sheep nursing their offspring. Serial 30-min infusion of 1MeDIQ (4 × 60 μg/60 μL) or vehicle were administered at 30-min interval from 10 AM to 2 PM. The experimental period in every ewe consisted of a nonsuckling period (10 AM-12 PM) and a suckling period (12 PM-2 PM). Blood samples were collected every 10 min, to measure plasma oxytocin concentration by RIA. In control sheep, oxytocin surges of high amplitude were observed during the suckling period. The oxytocin surges induced by suckling were significantly (P < 0.01) diminished in sheep receiving 1MeDIQ infusions as compared to those that received control infusions. However, no significant effect of 1MeDIQ was observed on basal oxytocin release, before suckling. Furthermore, oxytocin release, as measured by the area under the hormone response curve (AUC), was significantly decreased by the administration of 1MeDIQ during the suckling period. This study shows that elimination of the effect of salsolinol within the central nervous system of lactating sheep attenuates the oxytocin surge induced by suckling. Therefore, salsolinol may be an important factor in the oxytocin-stimulating pathway in lactating mammals. Copyright © 2016 Elsevier Inc. All rights reserved.

Oxytocin Acts in Nucleus Accumbens to Attenuate Methamphetamine Seeking and Demand.

PubMed

Cox, Brittney M; Bentzley, Brandon S; Regen-Tuero, Helaina; See, Ronald E; Reichel, Carmela M; Aston-Jones, Gary

2017-06-01

Evidence indicates that oxytocin, an endogenous peptide well known for its role in social behaviors, childbirth, and lactation, is a promising addiction pharmacotherapy. We employed a within-session behavioral-economic (BE) procedure in rats to examine oxytocin as a pharmacotherapy for methamphetamine (meth) addiction. The BE paradigm was modeled after BE procedures used to assess motivation for drugs in humans with addiction. The same BE variables assessed across species have been shown to predict later relapse behavior. Thus, the translational potential of preclinical BE studies is particularly strong. We tested the effects of systemic and microinfused oxytocin on demand for self-administered intravenous meth and reinstatement of extinguished meth seeking in male and female rats using a BE paradigm. Correlations between meth demand and meth seeking were assessed. Female rats showed greater demand (i.e., motivation) for meth compared with male rats. In both male and female rats, meth demand predicted reinstatement of meth seeking, and systemic oxytocin decreased demand for meth and attenuated reinstatement to meth seeking. Oxytocin was most effective at decreasing meth demand and seeking in rats with the strongest motivation for drug. Finally, these effects of systemic oxytocin were mediated by actions in the nucleus accumbens. Oxytocin decreases meth demand and seeking in both sexes, and these effects depend on oxytocin signaling in the nucleus accumbens. Overall, these data indicate that development of oxytocin-based therapies may be a promising treatment approach for meth addiction in humans. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Oxytocin acts in nucleus accumbens to attenuate methamphetamine seeking and demand

PubMed Central

Cox, Brittney M; Bentzley, Brandon S; Regen-Tuero, Helaina; See, Ronald E; Reichel, Carmela M; Aston-Jones, Gary

2016-01-01

Background Evidence indicates that oxytocin, an endogenous peptide well known for its role in social behaviors, childbirth and lactation, is a promising addiction pharmacotherapy. We employed a within-session behavioral-economic (BE) procedure in rats to examine oxytocin as a pharmacotherapy for methamphetamine (meth) addiction. The BE paradigm was modeled after BE procedures used to assess motivation for drugs in human addicts. Importantly, the same BE variables assessed across species have been shown to predict later relapse behavior. Thus, the translational potential of preclinical BE studies is particularly strong. Methods We tested the effects of systemic and microinfused oxytocin on demand for self-administered i.v. meth and reinstatement of extinguished meth-seeking in male and female rats using a behavioral economics paradigm. Correlations between meth demand and meth seeking were assessed. Results Females showed greater demand (i.e., motivation) for meth compared to males. In both males and females, meth demand predicted reinstatement of meth-seeking, and systemic oxytocin decreased demand for meth and attenuated reinstatement to meth seeking. Oxytocin was most effective at decreasing meth demand and seeking in rats with the strongest motivation for drug. Finally, we found that these effects of systemic oxytocin were mediated by actions in the nucleus accumbens (NAc). Discussion Oxytocin decreases meth demand and seeking in both sexes, and these effects depend on oxytocin signaling in the NAc. Overall, these data indicate that development of oxytocin-based therapies may be a promising treatment approach for meth addiction in humans. PMID:28110822

Oxytocin selectively moderates negative cognitive appraisals in high trait anxious males.

PubMed

Alvares, Gail A; Chen, Nigel T M; Balleine, Bernard W; Hickie, Ian B; Guastella, Adam J

2012-12-01

The mammalian neuropeptide oxytocin has well-characterized effects in facilitating prosocial and affiliative behavior. Additionally, oxytocin decreases physiological and behavioral responses to social stress. In the present study we investigated the effects of oxytocin on cognitive appraisals after a naturalistic social stress task in healthy male students. In a randomized, double-blind, placebo-controlled trial, 48 participants self-administered either an oxytocin or placebo nasal spray and, following a wait period, completed an impromptu speech task. Eye gaze to a pre-recorded video of an audience displayed during the task was simultaneously collected. After the speech, participants completed questionnaires assessing negative cognitive beliefs about speech performance. Whilst there was no overall effect of oxytocin compared to placebo on either eye gaze or questionnaire measures, there were significant positive correlations between trait levels of anxiety and negative self-appraisals following the speech. Exploratory analyses revealed that whilst higher trait anxiety was associated with increasingly poorer perceptions of speech performance in the placebo group, this relationship was not found in participants administered oxytocin. These results provide preliminary evidence to suggest that oxytocin may reduce negative cognitive self-appraisals in high trait anxious males. It adds to a growing body of evidence that oxytocin seems to attenuate negative cognitive responses to stress in anxious individuals. Copyright © 2012 Elsevier Ltd. All rights reserved.

On the role of oxytocin in borderline personality disorder.

PubMed

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

Transient oxytocin signaling primes the development and function of excitatory hippocampal neurons

PubMed Central

Ripamonti, Silvia; Ambrozkiewicz, Mateusz C; Guzzi, Francesca; Gravati, Marta; Biella, Gerardo; Bormuth, Ingo; Hammer, Matthieu; Tuffy, Liam P; Sigler, Albrecht; Kawabe, Hiroshi; Nishimori, Katsuhiko; Toselli, Mauro; Brose, Nils; Parenti, Marco; Rhee, JeongSeop

2017-01-01

Beyond its role in parturition and lactation, oxytocin influences higher brain processes that control social behavior of mammals, and perturbed oxytocin signaling has been linked to the pathogenesis of several psychiatric disorders. However, it is still largely unknown how oxytocin exactly regulates neuronal function. We show that early, transient oxytocin exposure in vitro inhibits the development of hippocampal glutamatergic neurons, leading to reduced dendrite complexity, synapse density, and excitatory transmission, while sparing GABAergic neurons. Conversely, genetic elimination of oxytocin receptors increases the expression of protein components of excitatory synapses and excitatory synaptic transmission in vitro. In vivo, oxytocin-receptor-deficient hippocampal pyramidal neurons develop more complex dendrites, which leads to increased spine number and reduced γ-oscillations. These results indicate that oxytocin controls the development of hippocampal excitatory neurons and contributes to the maintenance of a physiological excitation/inhibition balance, whose disruption can cause neurobehavioral disturbances. DOI: http://dx.doi.org/10.7554/eLife.22466.001 PMID:28231043

Selective influences of oxytocin on the evaluative processing of social stimuli

PubMed Central

Norman, Greg J; Cacioppo, John T; Morris, John S; Karelina, Kate; Malarkey, William B; DeVries, A Courtney; Berntson, Gary G

2013-01-01

The neuropeptide oxytocin has been implicated in a wide range of social processes, such as pair bonding, affiliation, and social judgments that may contribute to normal adjustment and psychiatric states. The present experimental study sought to elucidate potential underlying mechanisms by which oxytocin may impact social processes by examining the effects of intranasal oxytocin on basic evaluative processes. Subjects rated slide stimuli from the International Affective Picture System, varying across multiple categories (pleasant, neutral, unpleasant) and social content. Separate ratings for arousal and for the positive and negative components of valence were obtained in the context of a bivariate evaluative space model. Oxytocin did not have an independent significant effect on positivity or negativity ratings, but instead oxytocin treatment altered the interaction between these component processes for social, relative to non-social stimuli regardless of valence conditions. Specifically, oxytocin, relative to vehicle, significantly decreased arousal ratings to threatening human stimuli without altering ratings of threatening animal stimuli. These results indicate that oxytocin may exert its effects through dynamic alterations in the partially separable neural substrates mediating arousal as well as positive and negative evaluations of social stimuli. PMID:20498133

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

PubMed

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.

Maternal oxytocin response predicts mother-to-infant gaze

USDA-ARS?s Scientific Manuscript database

The neuropeptide oxytocin is importantly implicated in the emergence and maintenance of maternal behavior that forms the basis of the mother–infant bond. However, no research has yet examined the specific association between maternal oxytocin and maternal gaze, a key modality through which the mothe...

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

PubMed Central

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 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. PMID:20160081

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

PubMed

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.

Investigation of pyrazolo-sulfonamides as putative small molecule oxytocin receptor agonists.

PubMed

Katte, Timothy A; Reekie, Tristan A; Werry, Eryn L; Jorgensen, William T; Boyd, Rochelle; Wong, Erick C N; Gulliver, Damien W; Connor, Mark; Kassiou, Michael

2017-08-18

The neuropeptide oxytocin has been implicated in multiple central nervous system functions in mammalian species. Increased levels have been reported to improve trust, alleviate symptoms related to autism and social phobias, and reduce social anxiety. Hoffman-La Roche published a patent claiming to have found potent small molecule oxytocin receptor agonists, smaller than the first non-peptide oxytocin agonist reported, WAY 267,464. We selected two of the more potent compounds from the patent and, in addition, created WAY 267,464 hybrid structures and determined their oxytocin and vasopressin receptor activity. Human embryonic kidney and Chinese hamster ovary cells were used for the expression of oxytocin or vasopressin 1a receptors and activity assessed via IP1 accumulation assays and calcium FLIPR assays. The results concluded that the reported compounds in the patent and the hybrid structures have no activity at the oxytocin or vasopressin 1a receptors. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Preclinical Testing of Novel Oxytocin Receptor Activators in Models of Autism Phenotypes

DTIC Science & Technology

2015-11-01

evaluated one synthetic oxytocin agonist, Compound 39, and one oxytocin metabolite, for efficacy against social deficits in BALB/cByJ mice, and we are...currently evaluating a second oxytocin metabolite for prosocial effects. Overall, we have successfully validated three mouse models as preclinical...to, first, prioritize synthetic compounds that activate the oxytocin receptor using cell-based assays, and secondly, evaluate the therapeutic efficacy

Preclinical Testing of Novel Oxytocin Receptor Activators in Models of Autism Phenotypes

DTIC Science & Technology

2015-11-01

knockdown mouse. We have also evaluated one synthetic oxytocin agonist, Compound 39, and one oxytocin metabolite, for efficacy against social deficits in...BALB/cByJ mice, and we are currently evaluating a second oxytocin metabolite for prosocial effects. Overall, we have successfully validated three...secondly, evaluate the therapeutic efficacy of the top molecules in the characterized mouse lines (compound 39, carbetocin, and the oxytocin derivatives OT

Oxytocin regimen for labor augmentation, labor progression, and perinatal outcomes.

PubMed

Zhang, Jun; Branch, D Ware; Ramirez, Mildred M; Laughon, S Katherine; Reddy, Uma; Hoffman, Mathew; Bailit, Jennifer; Kominiarek, Michelle; Chen, Zhen; Hibbard, Judith U

2011-08-01

To examine the effects and safety of high-dose (compared with low-dose) oxytocin regimen for labor augmentation on perinatal outcomes. Data from the Consortium on Safe Labor were used. A total of 15,054 women from six hospitals were eligible for the analysis. Women were grouped based on their oxytocin starting dose and incremental dosing of 1, 2, and 4 milliunits/min. Duration of labor and a number of maternal and neonatal outcomes were compared among these three groups stratified by parity. Multivariable logistic regression and generalized linear mixed model were used to adjust for potential confounders. Oxytocin regimen did not affect the rate of cesarean delivery or other perinatal outcomes. Compared with 1 milliunit/min, the regimens starting with 2 milliunits/min and 4 milliunits/min reduced the duration of first stage by 0.8 hours (95% confidence interval 0.5-1.1) and 1.3 hours (1.0-1.7), respectively, in nulliparous women. No effect was observed on the second stage of labor. Similar patterns were observed in multiparous women. High-dose regimen was associated with a reduced risk of meconium stain, chorioamnionitis, and newborn fever in multiparous women. High-dose oxytocin regimen (starting dose at 4 milliunits/min and increment of 4 millliunits/min) is associated with a shorter duration of first-stage of labor for all parities without increasing the cesarean delivery rate or adversely affecting perinatal outcomes. II.

Intranasal oxytocin administration in relationship to social behaviour in domestic pigs.

PubMed

Camerlink, Irene; Reimert, Inonge; Bolhuis, J Elizabeth

2016-09-01

Intranasal administration of oxytocin has been shown to alter positive and negative social behaviour. Positive social behaviour in pigs (Sus scrofa) may be expressed through gentle social nosing, and greater insight in the specific expression hereof might contribute to the current search for positive indicators of animal welfare. We investigated whether oxytocin alters social nosing and whether this is specific to nose-body or nose-nose contact. Sixty-four focal female pigs of 13weeks of age (out of 16 groups) were given oxytocin (24IU dose) and saline (placebo) intranasally once on two consecutive days. The frequency of nose-to-nose contact and nose-to-body contact was recorded upon pigs' return in the home pen after being for 10min located in a separate area near pen mates undergoing a positive or negative event or not. The effect of intranasal oxytocin depended on the social context in which pigs were studied. Control pigs, which were not exposed to positively or negatively aroused pen mates, gave and received less nose-nose contact after oxytocin administration than after saline administration. Pigs exposed to positively aroused pen mates also tended to give less nose contact when given oxytocin compared to saline, whereas pigs exposed to negatively aroused pen mates and administered oxytocin tended to receive more nose contact. Nose-body contact was lowest in groups of negative social context, suggesting an effect of emotional state on social nosing. In contrast to nose-nose contact, nose-body contact was unaffected by oxytocin treatment. The relationship between social nosing and oxytocin merits further research. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications

PubMed Central

Freeman, Sara M.; Young, Larry J.

2016-01-01

In the last several decades, sophisticated experimental techniques have been used to determine the neurobiology of the oxytocin and vasopressin systems in rodents. Using a suite of methodologies, including electrophysiology, site-specific selective pharmacology, receptor autoradiography, in vivo microdialysis, and genetic and optogenetic manipulations, we have gained unprecedented knowledge about how these neuropeptides engage neural circuits to regulate behaviour, particularly social behaviour. Based on this foundation of information from rodent studies, we have started generating new hypotheses and frameworks about how the oxytocin and vasopressin systems could be acting in humans to influence social cognition. However, despite the recent inundation of publications using intranasal oxytocin in humans, we still know very little about the neurophysiology of the oxytocin system in primates more broadly. Furthermore, the design and analysis of these human studies have remained largely uninformed of the potential neurobiological mechanisms underlying their findings. Although the methods available for studying the oxytocin and vasopressin systems in humans are incredibly limited as a result of practical and ethical considerations, there is great potential to fill the gaps in our knowledge by developing better nonhuman primate models of social functioning. Behavioural pharmacology and receptor autoradiography have been used to study the oxytocin and vasopressin systems in nonhuman primates, and there is now great potential to broaden our understanding of the neurobiology of these systems. In this review, we discuss comparative findings in receptor distributions in rodents and primates, with perspectives on the functionality of conserved regions of expression in these distinct mammalian clades. We also identify specific ways that established technologies can be used to answer basic research questions in primates. Finally, we highlight areas of future research in nonhuman

Effects of paternal deprivation on cocaine-induced behavioral response and hypothalamic oxytocin immunoreactivity and serum oxytocin level in female mandarin voles.

PubMed

Wang, Jianli; Fang, Qianqian; Yang, Chenxi

2017-09-15

Early paternal behavior plays a critical role in behavioral development in monogamous species. The vast majority of laboratory studies investigating the influence of parental behavior on cocaine vulnerability focus on the effects of early maternal separation. However, comparable studies on whether early paternal deprivation influences cocaine-induced behavioral response are substantially lacking. Mandarin vole (Microtus mandarinus) is a monogamous rodent with high levels of paternal care. After mandarin vole pups were subjected to early paternal deprivation, acute cocaine- induced locomotion, anxiety- like behavior and social behavior were examined in 45day old female pups, while hypothalamic oxytocin immunoreactivity and serum oxytocin level were also assessed. We found that cocaine increased locomotion and decreased social investigation, contact behavior and serum oxytocin level regardless of paternal care. Cocaine increased anxiety levels and decreased oxytocin immunoreactive neurons of the paraventricular nuclei and supraoptic nuclei in the bi-parental care group, whilst there were no specific effects in the paternal deprivation group. These results indicate that paternal deprivation results in different behavioral response to acute cocaine exposure in adolescents, which may be in part associated with the alterations in oxytocin immunoreactivity and peripheral OT level. Copyright © 2017 Elsevier B.V. All rights reserved.

Oxytocin attenuates deficits in social interaction but not recognition memory in a prenatal valproic acid-induced mouse model of autism.

PubMed

Hara, Yuta; Ago, Yukio; Higuchi, Momoko; Hasebe, Shigeru; Nakazawa, Takanobu; Hashimoto, Hitoshi; Matsuda, Toshio; Takuma, Kazuhiro

2017-11-01

Recent studies have reported that oxytocin ameliorates behavioral abnormalities in both animal models and individuals with autism spectrum disorders (ASD). However, the mechanisms underlying the ameliorating effects of oxytocin remain unclear. In this study, we examined the effects of intranasal oxytocin on impairments in social interaction and recognition memory in an ASD mouse model in which animals are prenatally exposed to valproic acid (VPA). We found that a single intranasal administration of oxytocin restored social interaction deficits for up to 2h in mice prenatally exposed to VPA, but there was no effect on recognition memory impairments. Additionally, administration of oxytocin across 2weeks improved prenatal VPA-induced social interaction deficits for at least 24h. In contrast, there were no effects on the time spent sniffing in control mice. Immunohistochemical analysis revealed that intranasal administration of oxytocin increased c-Fos expression in the paraventricular nuclei (PVN), prefrontal cortex, and somatosensory cortex, but not the hippocampal CA1 and CA3 regions of VPA-exposed mice, suggesting the former regions may underlie the effects of oxytocin. These findings suggest that oxytocin attenuates social interaction deficits through the activation of higher cortical areas and the PVN in an ASD mouse model. Copyright © 2017 Elsevier Inc. All rights reserved.

Preclinical Testing of Novel Oxytocin Receptor Activators in Models of Autism Phenotypes

DTIC Science & Technology

2015-11-30

Grin1 knockdown mouse. We have also evaluated one synthetic oxytocin agonist, Compound 39, and one oxytocin metabolite, for efficacy against social...deficits in BALB/cByJ mice, and we are currently evaluating a second oxytocin metabolite for prosocial effects. Overall, we have successfully validated...secondly, evaluate the therapeutic efficacy of the top molecules in the characterized mouse lines (compound 39, carbetocin, and the oxytocin derivatives OT

Breastfeeding Outcomes After Oxytocin Use During Childbirth: An Integrative Review.

PubMed

Erickson, Elise N; Emeis, Cathy L

2017-07-01

Despite widespread use of exogenous synthetic oxytocin during the birth process, few studies have examined the effect of this drug on breastfeeding. Based on neuroscience research, endogenous oxytocin may be altered or manipulated by exogenous administration or by blocking normal function of the hormone or receptor. Women commonly cite insufficient milk production as their reason for early supplementation, jeopardizing breastfeeding goals. Researchers need to consider the role of birth-related medications and interventions on the production of milk. This article examines the literature on the role of exogenous oxytocin on breastfeeding in humans. Using the method described by Whittemore and Knafl, this integrative review of literature included broad search criteria within the PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane, and Scopus databases. Studies published in English associating a breastfeeding outcome in relation to oxytocin use during the birth process were included. Twenty-six studies from 1978 to 2015 met the criteria. Studies were analyzed according to the purpose of the research, measures and methods used, results, and confounding variables. The 26 studies reported 34 measures of breastfeeding. Outcomes included initiation and duration of breastfeeding, infant behavior, and physiologic markers of lactation. Timing of administration of oxytocin varied. Some studies reported on low-risk birth, while others included higher-risk experiences. Fifty percent of the results (17 of 34 measures) demonstrated an association between exogenous oxytocin and less optimal breastfeeding outcomes, while 8 of 34 measures (23%) reported no association. The remaining 9 measures (26%) had mixed findings. Breastfeeding intentions, parity, birth setting, obstetric risk, and indications for oxytocin use were inconsistently controlled among the studies. Research on breastfeeding and lactation following exogenous oxytocin exposure is limited

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

PubMed

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.

Targeting the Oxytocin System to Treat Addictive Disorders: Rationale and Progress to Date

PubMed Central

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

Intrapartum synthetic oxytocin reduce the expression of primitive reflexes associated with breastfeeding.

PubMed

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.

Oxytocin tempers calculated greed but not impulsive defense in predator-prey contests.

PubMed

De Dreu, Carsten K W; Scholte, H Steven; van Winden, Frans A A M; Ridderinkhof, K Richard

2015-05-01

Human cooperation and competition is modulated by oxytocin, a hypothalamic neuropeptide that functions as both hormone and neurotransmitter. Oxytocin's functions can be captured in two explanatory yet largely contradictory frameworks: the fear-dampening (FD) hypothesis that oxytocin has anxiolytic effects and reduces fear-motivated action; and the social approach/avoidance (SAA) hypothesis that oxytocin increases cooperative approach and facilitates protection against aversive stimuli and threat. We tested derivations from both frameworks in a novel predator-prey contest game. Healthy males given oxytocin or placebo invested as predator to win their prey's endowment, or as prey to protect their endowment against predation. Neural activity was registered using 3T-MRI. In prey, (fear-motivated) investments were fast and conditioned on the amygdala. Inconsistent with FD, oxytocin did not modulate neural and behavioral responding in prey. In predators, (greed-motivated) investments were slower, and conditioned on the superior frontal gyrus (SFG). Consistent with SAA, oxytocin reduced predator investment, time to decide and activation in SFG. Thus, whereas oxytocin does not incapacitate the impulsive ability to protect and defend oneself, it lowers the greedy and more calculated appetite for coming out ahead. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

A brief history of oxytocin and its role in modulating psychostimulant effects.

PubMed

Carson, Dean S; Guastella, Adam J; Taylor, Emily R; McGregor, Iain S

2013-03-01

Over the past century, the polypeptide oxytocin has played an important role in medicine with major highlights including the identification of its involvement in parturition and the milk let-down reflex. Oxytocin is now implicated in an extensive range of psychological phenomena including reward and memory processes and has been investigated as a treatment for several psychiatric disorders including addiction, anxiety, autism, and schizophrenia. In this review, we first provide an historical overview of oxytocin and describe key aspects of its physiological activity. We then outline some pharmacological limitations in this field of research before highlighting the role of oxytocin in a wide range of behavioral and neuronal processes. Finally, we review evidence for a modulatory role of oxytocin with regard to psychostimulant effects. Key findings suggest that oxytocin attenuates a broad number of cocaine and methamphetamine induced behaviors and associated neuronal activity in rodents. Evidence also outlines a role for oxytocin in the prosocial effects of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) in both rodents and humans. Clinical trials should now investigate the effectiveness of oxytocin as a novel intervention for psychostimulant addiction and should aim to determine its specific role in the therapeutic properties of MDMA that are currently being investigated.

Does oxytocin lead to emotional interference during a working memory paradigm?

PubMed

Tollenaar, Marieke S; Ruissen, M; Elzinga, B M; de Bruijn, E R A

2017-12-01

Oxytocin administration may increase attention to emotional information. We hypothesized that this augmented emotional processing might in turn lead to interference on concurrent cognitive tasks. To test this hypothesis, we examined whether oxytocin administration would lead to heightened emotional interference during a working memory paradigm. Additionally, moderating effects of childhood maltreatment were explored. Seventy-eight healthy males received 24 IU of intranasal oxytocin or placebo in a randomized placebo-controlled double-blind between-subjects study. A working memory task was performed during which neutral, positive, and negative distractors were presented. The main outcome observed was that oxytocin did not enhance interference by emotional information during the working memory task. There was a non-significant trend for oxytocin to slow down performance irrespective of distractor valence, while accuracy was unaffected. Exploratory analyses showed that childhood maltreatment was related to lower overall accuracy, but in the placebo condition only. However, the maltreated group sample size was very small precluding any conclusions on its moderating effect. Despite oxytocin's previously proposed role in enhanced emotional processing, no proof was found that this would lead to reduced performance on a concurrent cognitive task. The routes by which oxytocin exerts its effects on cognitive and social-emotional processes remain to be fully elucidated.

PLASMA OXYTOCIN LEVELS PREDICT SOCIAL CUE RECOGNITION IN INDIVIDUALS WITH SCHIZOPHRENIA

PubMed Central

Strauss, Gregory P.; Keller, William R.; Koenig, James I.; Gold, James M.; Frost, Katherine H.; Buchanan, Robert W.

2015-01-01

Lower endogenous levels of the neuropeptide oxytocin may be an important biological predictor of social cognition impairments in schizophrenia (SZ). Prior studies have demonstrated that lower-level social cognitive processes (e.g., facial affect perception) are significantly associated with reduced plasma oxytocin levels in SZ; however, it is unclear whether higher-level social cognition, which requires inferential processes and knowledge not directly presented in the stimulus, is associated with endogenous oxytocin. The current study explored the association between endogenous oxytocin levels and lower- and higher-level social cognition in 40 individuals diagnosed with SZ and 22 demographically matched healthy controls (CN). All participants received the Social Cue Recognition Test (SCRT), which presents participants with videotaped interpersonal vignettes and subsequent true/false questions related to concrete or abstract aspects of social interactions in the vignettes. Results indicated that SZ had significantly higher plasma oxytocin concentrations than CN. SZ and CN did not differ on SCRT hits, but SZ had more false positives and lower sensitivity scores than CN. Higher plasma oxytocin levels were associated with better sensitivity scores for abstract items in CN and fewer false positives for concrete items in individuals with SZ. Findings indicate that endogenous oxytocin levels predict accurate encoding of lower-level socially relevant information in SZ. PMID:25673435

Effect of oxytocin pretreatment on cannabis outcomes in a brief motivational intervention.

PubMed

Sherman, Brian J; Baker, Nathaniel L; McRae-Clark, Aimee L

2017-03-01

Motivational enhancement therapy (MET) is efficacious in reducing cannabis use, yet benefits are generally short-lived. Oxytocin is a hypothalamic neuropeptide that promotes prosocial behaviors and plays a role in drug-related neuroadaptations; as such, oxytocin may enhance the effect of MET on cannabis outcomes. Cannabis dependent adults were randomized to receive MET plus oxytocin (n =8) or placebo (n =8). Participants receiving oxytocin showed reductions in amount of cannabis used daily and number of sessions per day. Participants receiving placebo did not evidence significant reductions. Powered clinical trials of oxytocin-enhanced MET for cannabis use disorder are warranted. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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.

Dopamine and oxytocin interactions underlying behaviors: potential contributions to behavioral disorders.

PubMed

Baskerville, Tracey A; Douglas, Alison J

2010-06-01

Dopamine is an important neuromodulator that exerts widespread effects on the central nervous system (CNS) function. Disruption in dopaminergic neurotransmission can have profound effects on mood and behavior and as such is known to be implicated in various neuropsychiatric behavioral disorders including autism and depression. The subsequent effects on other neurocircuitries due to dysregulated dopamine function have yet to be fully explored. Due to the marked social deficits observed in psychiatric patients, the neuropeptide, oxytocin is emerging as one particular neural substrate that may be influenced by the altered dopamine levels subserving neuropathologic-related behavioral diseases. Oxytocin has a substantial role in social attachment, affiliation and sexual behavior. More recently, it has emerged that disturbances in peripheral and central oxytocin levels have been detected in some patients with dopamine-dependent disorders. Thus, oxytocin is proposed to be a key neural substrate that interacts with central dopamine systems. In addition to psychosocial improvement, oxytocin has recently been implicated in mediating mesolimbic dopamine pathways during drug addiction and withdrawal. This bi-directional role of dopamine has also been implicated during some components of sexual behavior. This review will discuss evidence for the existence dopamine/oxytocin positive interaction in social behavioral paradigms and associated disorders such as sexual dysfunction, autism, addiction, anorexia/bulimia, and depression. Preliminary findings suggest that whilst further rigorous testing has to be conducted to establish a dopamine/oxytocin link in human disorders, animal models seem to indicate the existence of broad and integrated brain circuits where dopamine and oxytocin interactions at least in part mediate socio-affiliative behaviors. A profound disruption to these pathways is likely to underpin associated behavioral disorders. Central oxytocin pathways may serve as a

Breaking the loop: oxytocin as a potential treatment for drug addiction.

PubMed

McGregor, Iain S; Bowen, Michael T

2012-03-01

Drug use typically occurs within a social context, and social factors play an important role in the initiation, maintenance and recovery from addictions. There is now accumulating evidence of an interaction between the neural substrates of affiliative behavior and those of drug reward, with a role for brain oxytocin systems in modulating acute and long-term drug effects. Early research in this field indicated that exogenous oxytocin administration can prevent development of tolerance to ethanol and opiates, the induction of stereotyped, hyperactive behavior by stimulants, and the withdrawal symptoms associated with sudden abstinence from drugs and alcohol. Additionally, stimulation of endogenous oxytocin systems is a key neurochemical substrate underlying the prosocial and empathogenic effects of party drugs such as MDMA (Ecstasy) and GHB (Fantasy). Brain oxytocin systems exhibit profound neuroplasticity and undergo major neuroadaptations as a result of drug exposure. Many drugs, including cocaine, opiates, alcohol, cannabis, MDMA and GHB cause long-term changes in markers of oxytocin function and this may be linked to enduring deficits in social behavior that are commonly observed in laboratory animals repeatedly exposed to these drugs. Very recent preclinical studies have illustrated a remarkable ability of exogenously delivered oxytocin to inhibit stimulant and alcohol self-administration, to alter associated drug-induced changes in dopamine, glutamate and Fos expression in cortical and basal ganglia sites, and to prevent stress and priming-induced relapse to drug seeking. Oxytocin therefore has fascinating potential to reverse the corrosive effects of long-term drugs abuse on social behavior and to perhaps inoculate against future vulnerability to addictive disorders. The results of clinical studies examining intranasal oxytocin effects in humans with drug use disorders are eagerly awaited. This article is part of a Special Issue entitled Oxytocin, Vasopressin

Current findings on the role of oxytocin in the regulation of food intake.

PubMed

Spetter, Maartje S; Hallschmid, Manfred

2017-07-01

In the face of the alarming prevalence of obesity and its associated metabolic impairments, it is of high basic and clinical interest to reach a complete understanding of the central nervous pathways that establish metabolic control. In recent years, the hypothalamic neuropeptide oxytocin, which is primarily known for its involvement in psychosocial processes and reproductive behavior, has received increasing attention as a modulator of metabolic function. Oxytocin administration to the brain of normal-weight animals, but also animals with diet-induced or genetically engineered obesity reduces food intake and body weight, and can also increase energy expenditure. Up to now, only a handful of studies in humans have investigated oxytocin's contribution to the regulation of eating behavior. Relying on the intranasal pathway of oxytocin administration, which is a non-invasive strategy to target central nervous oxytocin receptors, these experiments have yielded some promising first results. In normal-weight and obese individuals, intranasal oxytocin acutely limits meal intake and the consumption of palatable snacks. It is still unclear to which extent - or if at all - such metabolic effects of oxytocin in humans are conveyed or modulated by oxytocin's impact on cognitive processes, in particular on psychosocial function. We shortly summarize the current literature on oxytocin's involvement in food intake and metabolic control, ponder potential links to social and cognitive processes, and address future perspectives as well as limitations of oxytocin administration in experimental and clinical contexts. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Oxytocin in the ventromedial hypothalamic nucleus reduces feeding and acutely increases energy expenditure

PubMed Central

Noble, Emily E.; Billington, Charles J.; Kotz, Catherine M.

2014-01-01

Central oxytocin reduces food intake and increases energy expenditure. The ventromedial hypothalamic nucleus (VMN) is associated with energy balance and contains a high density of oxytocin receptors. We hypothesized that oxytocin in the VMN is a negative regulator of energy balance acting to reduce feeding and increase energy expenditure. To test this idea, oxytocin or vehicle was injected directly into the VMN of Sprague-Dawley rats during fasted and nonfasted conditions. Energy expenditure (via indirect calorimetry) and spontaneous physical activity (SPA) were recorded simultaneously. Animals were also exposed to a conditioned taste aversion test, to determine whether oxytocin's effects on food intake were associated with malaise. When food was available during testing, oxytocin-induced elevations in energy expenditure lasted for 1 h, after which overall energy expenditure was reduced. In the absence of food during the testing period, oxytocin similarly increased energy expenditure during the first hour, but differences in 12-h energy expenditure were eliminated, implying that the differences may have been due to the thermic effects of feeding (digestion, absorption, and metabolic processing). Oxytocin acutely elevated SPA and reduced feeding at doses that did not cause a conditioned taste aversion during both the fed and fasted states. Together, these data suggest that oxytocin in the VMN promotes satiety and acutely elevates energy expenditure and SPA and implicates the VMN as a relevant site for the antiobesity effects of oxytocin. PMID:24990860

Effect of long-term intranasal oxytocin on sexual dysfunction in premenopausal and postmenopausal women: a randomized trial.

PubMed

Muin, Dana A; Wolzt, Michael; Marculescu, Rodrig; Sheikh Rezaei, Safoura; Salama, Mohamed; Fuchs, Carola; Luger, Anton; Bragagna, Elia; Litschauer, Brigitte; Bayerle-Eder, Michaela

2015-09-01

To assess the effect of on-demand intranasal oxytocin administration on female sexual function and activity. Randomized, prospective, double-blind, placebo-controlled, crossover trial with duration of 22 weeks. Academic medical center. Thirty pre-and postmenopausal women with sexual dysfunction. Over 8 weeks, intranasal oxytocin (32 IU) or placebo self-administered by women within 50 minutes before sexual intercourse; after a washout period of 2 weeks, crossover with patients switched to the alternate group for another 8 weeks. Primary outcome parameter: Female Sexual Function Index (FSFI); secondary outcome parameters: Female Sexual Distress Scale (FSDS), Sexual Quality of Life-Female (SQOL-F), Sexual Interest and Desire Inventory-Female (SIDI-F), and Hamilton depression scale (HDS). After oxytocin and placebo, the FSFI score increased by 26% and 31%, SQOL-F score by 144% and 125%, and SIDI-F score by 29% and 23%, respectively (repeated measures analysis of variance between groups). After oxytocin and placebo, the FSDS score decreased by 36% and 45%, respectively (repeated measures analysis of variance between groups). There was no statistically significant treatment, sequence (placebo first/second), or interaction effect. Long-term intranasal oxytocin and placebo administration both improved sexual function and symptoms of depression in women over time with no treatment, sequence (placebo first/second), or interaction effect. NCT02229721. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Oxytocin modulates meta-mood as a function of age and sex

PubMed Central

Ebner, Natalie C.; Horta, Marilyn; Lin, Tian; Feifel, David; Fischer, Håkan; Cohen, Ronald A.

2015-01-01

Attending to and understanding one’s own feelings are components of meta-mood and constitute important socio-affective skills across the entire lifespan. Growing evidence suggests a modulatory role of the neuropeptide oxytocin on various socio-affective processes. Going beyond previous work that almost exclusively examined young men and perceptions of emotions in others, the current study investigated effects of intranasal oxytocin on meta-mood in young and older men and women. In a double-blind between-group design, participants were randomly assigned to self-administer either intranasal oxytocin or a placebo before responding to items from the Trait Meta-Mood Scale (TMMS) about attention to feelings and clarity of feelings. In contrast to older women, oxytocin relative to placebo increased attention to feelings in older men. Oxytocin relative to placebo enhanced meta-mood in young female participants but reduced it in older female participants. This pattern of findings supports an age- and sex-differential modulatory function of the neuropeptide oxytocin on meta-mood, possibly associated with neurobiological differences with age and sex. PMID:26441637

Oxytocin receptor gene polymorphisms are associated with human directed social behavior in dogs (Canis familiaris).

PubMed

Kis, Anna; Bence, Melinda; Lakatos, Gabriella; Pergel, Enikő; Turcsán, Borbála; Pluijmakers, Jolanda; Vas, Judit; Elek, Zsuzsanna; Brúder, Ildikó; Földi, Levente; Sasvári-Székely, Mária; Miklósi, Adám; Rónai, Zsolt; Kubinyi, Enikő

2014-01-01

The oxytocin system has a crucial role in human sociality; several results prove that polymorphisms of the oxytocin receptor gene are related to complex social behaviors in humans. Dogs' parallel evolution with humans and their adaptation to the human environment has made them a useful species to model human social interactions. Previous research indicates that dogs are eligible models for behavioral genetic research, as well. Based on these previous findings, our research investigated associations between human directed social behaviors and two newly described (-212AG, 19131AG) and one known (rs8679684) single nucleotide polymorphisms (SNPs) in the regulatory regions (5' and 3' UTR) of the oxytocin receptor gene in German Shepherd (N = 104) and Border Collie (N = 103) dogs. Dogs' behavior traits have been estimated in a newly developed test series consisting of five episodes: Greeting by a stranger, Separation from the owner, Problem solving, Threatening approach, Hiding of the owner. Buccal samples were collected and DNA was isolated using standard protocols. SNPs in the 3' and 5' UTR regions were analyzed by polymerase chain reaction based techniques followed by subsequent electrophoresis analysis. The gene-behavior association analysis suggests that oxytocin receptor gene polymorphisms have an impact in both breeds on (i) proximity seeking towards an unfamiliar person, as well as their owner, and on (ii) how friendly dogs behave towards strangers, although the mediating molecular regulatory mechanisms are yet unknown. Based on these results, we conclude that similarly to humans, the social behavior of dogs towards humans is influenced by the oxytocin system.

Schizophrenia and alcohol dependence: diverse clinical effects of oxytocin and their evolutionary origins.

PubMed

Pedersen, Cort A

2014-09-11

Beginning in 1979 with the first report that central administration of oxytocin stimulates maternal behavior in virgin rats, decades of animal research and more recent human studies have demonstrated that oxytocin has many pro-social effects. These many findings suggest that oxytocin may be an effective treatment for social deficits that are hallmark features of disorders such as autism and schizophrenia. Effects in preclinical animal models also imply that oxytocin may be an efficacious pharmacotherapy in a wide range of psychiatric disorders including psychoses and addictions. To date, 3 small clinical trials found that daily intranasal oxytocin treatment for 2-8 weeks significantly reduced psychotic symptoms in schizophrenia. Two of these trials also found improvement in social cognition or neurocognition, areas in which patients have significant deficiencies that do not respond to conventional antipsychotic treatment and contribute to disability. In another small trial, intranasal oxytocin potently blocked alcohol withdrawal. After reviewing the rationale for these trials, they are described in more detail. Questions are then asked followed by discussions of the large gaps in our knowledge about brain oxytocin systems in humans. The hope is to highlight important directions for future investigations of the role of oxytocin in the pathophysiology of psychotic disorders and addictions and to extend clinical research in these areas. Heretofore unrecognized roles for which oxytocin may have been selected during the evolution of placental mammalian maternal-infant and other social attachments are considered as possible origins of oxytocin antipsychotic and antiaddiction effects.This article is part of a Special Issue entitled Oxytocin and Social Behav. Copyright © 2014. Published by Elsevier B.V.

Oxytocin conditions trait-based rule adherence

PubMed Central

De Dreu, Carsten K.W.

2017-01-01

Abstract Rules, whether in the form of norms, taboos or laws, regulate and coordinate human life. Some rules, however, are arbitrary and adhering to them can be personally costly. Rigidly sticking to such rules can be considered maladaptive. Here, we test whether, at the neurobiological level, (mal)adaptive rule adherence is reduced by oxytocin—a hypothalamic neuropeptide that biases the biobehavioural approach-avoidance system. Participants (N = 139) self-administered oxytocin or placebo intranasally, and reported their need for structure and approach-avoidance sensitivity. Next, participants made binary decisions and were given an arbitrary rule that demanded to forgo financial benefits. Under oxytocin, participants violated the rule more often, especially when they had high need for structure and high approach sensitivity. Possibly, oxytocin dampens the need for a highly structured environment and enables individuals to flexibly trade-off internal desires against external restrictions. Implications for the treatment of clinical disorders marked by maladaptive rule adherence are discussed. PMID:27664999

Empathy toward strangers triggers oxytocin release and subsequent generosity.

PubMed

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.

Electrophysiological correlates of oxytocin-induced enhancement of social performance monitoring.

PubMed

de Bruijn, Ellen R A; Ruissen, Margit I; Radke, Sina

2017-10-01

Altered performance monitoring has been demonstrated after administration of different pharmacological compounds and in various clinical populations, such as excessive neurophysiological responses to mistakes in anxiety disorders. Here, a novel social pharmacological approach was applied to investigate whether oxytocin administration (24 IU) enhances performance monitoring for errors that have negative consequences for another individual, so-called social mistakes. Healthy male volunteers (N = 24) participated in a placebo-controlled crossover design. EEG measures were obtained while pairs of participants performed a speeded choice reaction-time task in an individual and social context. Following oxytocin administration, error-related negativity amplitudes were increased for social compared with individual mistakes. This increase was not found in the placebo condition. No effects of oxytocin were present in the individual context. The current study shows that oxytocin enhances performance monitoring specifically for social mistakes. This outcome is in line with a presumed role for oxytocin in salience attribution to social cues and underlines its context-dependency. Combining these processes may thus open up new research avenues and advance our understanding of individual differences in performance monitoring and oxytocin responses from a social neurocognitive, pharmacological and clinical perspective. © The Author (2017). Published by Oxford University Press.

Low oxytocin levels are related to alexithymia in anorexia nervosa.

PubMed

Schmelkin, Cindy; Plessow, Franziska; Thomas, Jennifer J; Gray, Emily K; Marengi, Dean A; Pulumo, Reitumetse; Silva, Lisseth; Miller, Karen K; Hadjikhani, Nouchine; Franko, Debra L; Eddy, Kamryn T; Lawson, Elizabeth A

2017-11-01

Anorexia nervosa is associated with social-emotional functioning deficits and low levels of the social neurohormone oxytocin, even after weight gain. The relationship between low oxytocin levels and social-emotional functioning impairment has not been studied. We performed a cross-sectional study of 79 women (19 who were less than 85% of ideal body weight [IBW] with anorexia nervosa [AN], 26 who were 90-120% IBW with a history of AN [AN-WR], and 34 who were 90-120% IBW with no eating disorder history [H]). We administered the Eating Disorder Examination-Questionnaire (EDE-Q), Leibowitz Social Anxiety Scale-Self Report (LSAS-SR), Dimensional Assessment of Personality Pathology-Basic Questionnaire (DAPP-BQ; suspiciousness and insecure attachment subscales), and the Toronto Alexithymia Scale (TAS-20). We also analyzed fasting serum oxytocin levels. Most measures of social-emotional functioning showed impairment in women with AN and AN-WR compared to H. Oxytocin levels were low in AN-WR compared to H. Across groups, low oxytocin levels were associated with difficulty identifying feelings (r = -.45, p = .008) and overall alexithymia (r = -.34, p = .0489). We speculate that low oxytocin levels may contribute to alexithymia in women with anorexia nervosa. © 2017 Wiley Periodicals, Inc.

BEYOND LABOR: THE ROLE OF NATURAL AND SYNTHETIC OXYTOCIN IN THE TRANSITION TO MOTHERHOOD

PubMed Central

Bell, Aleeca F.; Erickson, Elise N.; Carter, C. Sue

2013-01-01

Endogenous oxytocin is a key component in the transition to motherhood affecting molecular pathways that buffer stress reactivity, support positive mood, and regulate healthy mothering behaviors (including lactation). Synthetic oxytocin is widely used throughout labor and postpartum care in modern obstetrics. Yet research on the implications beyond labor of maternal exposure to perinatal synthetic oxytocin is rare. In this article, we review oxytocin-related biological pathways and behaviors associated with the transition to motherhood, and evidence supporting the need for further research on potential effects of intrapartum oxytocin beyond labor. We include a primer on oxytocin at the molecular level. PMID:24472136

Evidence for Alterations in Stimulatory G proteins and Oxytocin Levels in Children with Autism

PubMed Central

Jacobson, Jill D.; Ellerbeck, Kathryn A.; Kelly, Kelsie A.; Fleming, Kandace K.; Jamison, T. Rene; Coffey, Charles W.; Smith, Catherine M.; Reese, R. Matthew; Sands, Scott A.

2014-01-01

The neurotransmitter oxytocin plays an important role in social affiliation. Low oxytocin levels and defects in the oxytocin receptor have been reported in childhood autism. However, little is known about oxytocin’s post-receptor signaling pathways in autism. Oxytocin signals via stimulatory and inhibitory G proteins. c-fos mRNA expression has been used as a marker of OT signaling as well as of G protein signaling. Herein, we hypothesized that oxytocin and its signaling pathways would be altered in children with autism. We measured plasma oxytocin levels by ELISA, G-protein and c-fos mRNA by PCR, and G proteins by immunoblot in cultured peripheral blood mononuclear cells (PBMCs) in children with autism and in age-matched controls. Males with autism displayed elevated oxytocin levels compared to controls (p<0.05). Children with autism displayed significantly higher mRNA for stimulatory G proteins compared to controls (p<0.05). Oxytocin levels correlated strongly positively with c-fos mRNA levels, but only in control participants (p<0.01). Oxytocin, G-protein, and c-fos mRNA levels correlated inversely with measures of social and emotional behaviors, but only in control participants. These data suggest that children with autism may exhibit a dysregulation in oxytocin and/or its signaling pathways. PMID:24485488

Hypopituitarism is associated with lower oxytocin concentrations and reduced empathic ability.

PubMed

Daughters, Katie; Manstead, Antony S R; Rees, D Aled

2017-07-01

Central diabetes insipidus is characterised by arginine vasopressin deficiency. Oxytocin is structurally related to vasopressin and is synthesised in the same hypothalamic nuclei, thus we hypothesised that patients with acquired central diabetes insipidus and anterior hypopituitarism would display an oxytocin deficiency. Moreover, psychological research has demonstrated that oxytocin influences social and emotional behaviours, particularly empathic behaviour. We therefore further hypothesised that central diabetes insipidus patients would perform worse on empathy-related tasks, compared to age-matched and gender-matched clinical control (clinical control-isolated anterior hypopituitarism) and healthy control groups. Fifty-six participants (age 46.54 ± 16.30 yrs; central diabetes insipidus: n = 20, 8 males; clinical control: n = 15, 6 males; healthy control: n = 20, 7 males) provided two saliva samples which were analysed for oxytocin and completed two empathy tasks. Hypopituitary patients (both central diabetes insipidus and clinical control groups) had significantly lower oxytocin concentrations compared to healthy control participants. Hypopituitary patients also performed significantly worse on both the reading the mind in the eyes task and the facial expression recognition task compared to healthy control participants. Regression analyses further revealed that central diabetes insipidus patients' oxytocin concentrations significantly predicted their performance on easy items of the reading the mind in the eyes task. Hypopituitarism may therefore be associated with reduced oxytocin concentrations and impaired empathic ability. While further studies are needed to replicate these findings, our data suggest that oxytocin replacement may offer a therapeutic approach to improve psychological well-being in patients with hypopituitarism.

Restoring effects of oxytocin on the attentional preference for faces in autism.

PubMed

Kanat, M; Spenthof, I; Riedel, A; van Elst, L T; Heinrichs, M; Domes, G

2017-04-18

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 attention to neutral faces as compared to houses in a sample of 29 autistic individuals and 30 control participants using a dot-probe paradigm with two different presentation times (100 or 500 ms). A single dose of 24 IU oxytocin was administered in a randomized, double-blind placebo-controlled, cross-over design. Under placebo, ASD individuals paid less attention to faces presented for 500 ms than did controls. Oxytocin administration increased the allocation of attention toward faces in ASD to a level observed in controls. Secondary analyses revealed that these oxytocin effects primarily occurred in ASD individuals with high levels of social anxiety who were characterized by attentional avoidance of faces under placebo. Our results confirm a positive influence of intranasal oxytocin on social attention processes in ASD. Further, they suggest that oxytocin may in particular restore the attentional preference for facial information in ASD individuals with high social anxiety. We conclude that oxytocin's anxiolytic properties may partially account for its positive effects on socio-cognitive functioning in ASD, such as enhanced eye gaze and facial emotion recognition.

Prosocial effects of oxytocin in two mouse models of autism spectrum disorders.

PubMed

Teng, Brian L; Nonneman, Randal J; Agster, Kara L; Nikolova, Viktoriya D; Davis, Tamara T; Riddick, Natallia V; Baker, Lorinda K; Pedersen, Cort A; Jarstfer, Michael B; Moy, Sheryl S

2013-09-01

Clinical evidence suggests that oxytocin treatment improves social deficits and repetitive behavior in autism spectrum disorders (ASDs). However, the neuropeptide has a short plasma half-life and poor ability to penetrate the blood-brain barrier. In order to facilitate the development of more bioavailable oxytocinergic compounds as therapeutics to treat core ASD symptoms, small animal models must be validated for preclinical screens. This study examined the preclinical utility of two inbred mouse strains, BALB/cByJ and C58/J, that exhibit phenotypes relevant to core ASD symptoms. Mice from both strains were intraperitoneally administered oxytocin, using either acute or sub-chronic regimens. Acute oxytocin did not increase sociability in BALB/cByJ; however, sub-chronic oxytocin had significant prosocial effects in both BALB/cByJ and C58/J. Increased sociability was observed 24 h following the final oxytocin dose in BALB/cByJ, while prosocial effects of oxytocin emerged 1-2 weeks post-treatment in C58/J. Furthermore, acute oxytocin decreased motor stereotypy in C58/J and did not induce hypoactivity or anxiolytic-like effects in an open field test. This study demonstrates that oxytocin administration can attenuate social deficits and repetitive behavior in mouse models of ASD, dependent on dose regimen and genotype. These findings provide validation of the BALB/cByJ and C58/J models as useful platforms for screening novel drugs for intervention in ASDs and for elucidating the mechanisms contributing to the prosocial effects of oxytocin. Copyright © 2013 Elsevier Ltd. All rights reserved.

Prosocial effects of oxytocin in two mouse models of autism spectrum disorders

PubMed Central

Teng, Brian L.; Nonneman, Randal J.; Agster, Kara L.; Nikolova, Viktoriya D.; Davis, Tamara T.; Riddick, Natallia V.; Baker, Lorinda K.; Pedersen, Cort A.; Jarstfer, Michael B.; Moy, Sheryl S.

2013-01-01

Clinical evidence suggests that oxytocin treatment improves social deficits and repetitive behavior in autism spectrum disorders (ASDs). However, the neuropeptide has a short plasma half-life and poor ability to penetrate the blood-brain barrier. In order to facilitate the development of more bioavailable oxytocinergic compounds as therapeutics to treat core ASD symptoms, small animal models must be validated for preclinical screens. This study examined the preclinical utility of two inbred mouse strains, BALB/cByJ and C58/J, that exhibit phenotypes relevant to core ASD symptoms. Mice from both strains were intraperitoneally administered oxytocin, using either acute or sub-chronic regimens. Acute oxytocin did not increase sociability in BALB/cByJ; however, sub-chronic oxytocin had significant prosocial effects in both BALB/cByJ and C58/J. Increased sociability was observed 24 hours following the final oxytocin dose in BALB/cByJ, while prosocial effects of oxytocin emerged 1–2 weeks post-treatment in C58/J. Furthermore, acute oxytocin decreased motor stereotypy in C58/J and did not induce hypoactivity or anxiolytic-like effects in an open field test. This study demonstrates that oxytocin administration can attenuate social deficits and repetitive behavior in mouse models of ASD, dependent on dose regimen and genotype. These findings provide validation of the BALB/cByJ and C58/J models as useful platforms for screening novel drugs for intervention in ASDs and for elucidating the mechanisms contributing to the prosocial effects of oxytocin. PMID:23643748

Restoring effects of oxytocin on the attentional preference for faces in autism

PubMed Central

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 attention to neutral faces as compared to houses in a sample of 29 autistic individuals and 30 control participants using a dot-probe paradigm with two different presentation times (100 or 500 ms). A single dose of 24 IU oxytocin was administered in a randomized, double-blind placebo-controlled, cross-over design. Under placebo, ASD individuals paid less attention to faces presented for 500 ms than did controls. Oxytocin administration increased the allocation of attention toward faces in ASD to a level observed in controls. Secondary analyses revealed that these oxytocin effects primarily occurred in ASD individuals with high levels of social anxiety who were characterized by attentional avoidance of faces under placebo. Our results confirm a positive influence of intranasal oxytocin on social attention processes in ASD. Further, they suggest that oxytocin may in particular restore the attentional preference for facial information in ASD individuals with high social anxiety. We conclude that oxytocin's anxiolytic properties may partially account for its positive effects on socio-cognitive functioning in ASD, such as enhanced eye gaze and facial emotion recognition. PMID:28418399

A Heartfelt Response: Oxytocin Effects on Response to Social Stress in Men and Women

PubMed Central

Kubzansky, Laura D; Mendes, Wendy Berry; Appleton, Allison A.; Block, Jason; Adler, Gail K

2012-01-01

Background Animal research indicates that oxytocin is involved in social behavior, stress regulation, and positive physiologic adaptation. This study examines whether oxytocin enhances adaptive responses to social stress and compares effects between men and women. Methods Hypotheses were tested with a placebo-controlled, double-blind experiment. Social stress was induced. Changes in cardiovascular reactivity, affect, and behavior were assessed. Results Participants given oxytocin, relative to placebo, responded to social stress with a challenge orientation characterized by a benign pattern of cardiovascular reactivity. Gender differences emerged. Men given oxytocin reported less negative affect and had greater vagal rebound, while women given oxytocin reported more anger and had better math performance following social stress. Discussion Findings indicate oxytocin stimulates an approach-oriented cardiovascular profile during social stress, suggesting mechanisms by which oxytocin might improve physical health. However, before considering oxytocin as therapeutic or uniformly enhancing health, greater understanding of possible gender differences in effects is needed. PMID:22387929

Oxytocin Reduces Background Anxiety in a Fear-Potentiated Startle Paradigm: Peripheral vs Central Administration

PubMed Central

Ayers, Luke W; Missig, Galen; Schulkin, Jay; Rosen, Jeffrey B

2011-01-01

Oxytocin is known to have anti-anxiety and anti-stress effects. Using a fear-potentiated startle paradigm in rats, we previously demonstrated that subcutaneously administered oxytocin suppressed acoustic startle following fear conditioning compared with startle before fear conditioning (termed background anxiety), but did not have an effect on cue-specific fear-potentiated startle. The findings suggest oxytocin reduces background anxiety, an anxious state not directly related to cue-specific fear, but sustained beyond the immediate threat. The goal of the present study was to compare the effects of centrally and peripherally administered oxytocin on background anxiety and cue-specific fear. Male rats were given oxytocin either subcutaneously (SC) or intracerebroventricularly (ICV) into the lateral ventricles before fear-potentiated startle testing. Oxytocin doses of 0.01 and 0.1 μg/kg SC reduced background anxiety. ICV administration of oxytocin at doses from 0.002 to 20 μg oxytocin had no effect on background anxiety or cue-specific fear-potentiated startle. The 20 μg ICV dose of oxytocin did reduce acoustic startle in non-fear conditioned rats. These studies indicate that oxytocin is potent and effective in reducing background anxiety when delivered peripherally, but not when delivered into the cerebroventricular system. Oxytocin given systemically may have anti-anxiety properties that are particularly germane to the hypervigilance and exaggerated startle typically seen in many anxiety and mental health disorder patients. PMID:21796104

Intrapartum Synthetic Oxytocin Reduce the Expression of Primitive Reflexes Associated with Breastfeeding

PubMed Central

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

2015-01-01

Abstract Aim: 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. Materials and Methods: 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. Results: 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). Conclusions: Intrapartum oxytocin administration might inhibit the expression of several primitive neonatal reflexes associated with breastfeeding. This correlation does not seem to be dose-dependent. PMID:25785487

Reversal of social deficits by subchronic oxytocin in two autism mouse models

PubMed Central

Teng, Brian L.; Nikolova, Viktoriya D.; Riddick, Natallia V.; Agster, Kara L.; Crowley, James J.; Baker, Lorinda K.; Koller, Beverly H.; Pedersen, Cort A.; Jarstfer, Michael B.; Moy, Sheryl S.

2016-01-01

Social deficits are a hallmark feature of autism spectrum disorder (ASD) and related developmental syndromes. Although there is no standard treatment for social dysfunction, clinical studies have identified oxytocin as a potential therapeutic with prosocial efficacy. We have previously reported that peripheral oxytocin treatment can increase sociability and ameliorate repetitive stereotypy in adolescent mice from the C58/J model of ASD-like behavior. In the present study, we determined that prosocial oxytocin effects were not limited to the adolescent period, since C58/J mice, tested in adulthood, demonstrated significant social preference up to 2 weeks following subchronic oxytocin treatment. Oxytocin was also evaluated in adult mice with underexpression of the N-methyl-D-aspartate receptor NR1 subunit (encoded by Grin1), a genetic model of autism- and schizophrenia- like behavior. Subchronic oxytocin had striking prosocial efficacy in male Grin1 knockdown mice; in contrast, chronic regimens with clozapine (66 mg/kg/day) or risperidone (2 mg/kg/day) failed to reverse deficits in sociability. Neither the subchronic oxytocin regimen, nor chronic treatment with clozapine or risperidone, reversed impaired prepulse inhibition in the Grin1 knockdown mice. Overall, these studies demonstrate oxytocin can enhance sociability in mouse models with divergent genotypes and behavioral profiles, adding to the evidence that this neurohormone could have therapeutic prosocial efficacy across a spectrum of developmental disorders. PMID:26748053

Oxytocin increases extrapancreatic glucagon secretion and glucose production in pancreatectomized dogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Altszuler, N.; Puma, F.; Winkler, B.

1986-05-01

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-/sup 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 ..mu..U/kg/min) caused a rise in plasma glucagon and glucose levels,more » 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.« less

Effects of Intranasal Oxytocin on Aggressive Responding in Antisocial Personality Disorder.

PubMed

Alcorn, Joseph L; Rathnayaka, Nuvan; Swann, Alan C; Moeller, F Gerard; Lane, Scott D

2015-12-01

The oxytocin receptor is important in several domains of social behavior, and administration of oxytocin modulates social responding in several mammalian species, including humans. Oxytocin has both therapeutic and scientific potential for elucidating the neural and behavioral mechanisms governing social behavior. In the present study, operationally-defined aggressive behavior of six males with Antisocial Personality Disorder (ASPD) was measured following acute intranasal oxytocin dosing (12, 24, and 48 international units) and placebo, using a well-validated laboratory task of human aggression (Point-Subtraction Aggression Paradigm, or PSAP). The PSAP provides participants with concurrently available monetary-earning and operationally-defined aggressive response options, maintained by fixed ratio schedules of consequences. Shifts in response rates and inter-response time (IRT) distributions were observed on the aggressive response option following oxytocin doses, relative to placebo. Few changes were observed in monetary-reinforced responding. However, across participants the direction and magnitude of changes in aggressive responding were not systematically related to dose. No trends were observed between psychometric or physiological data and oxytocin dosing or aggressive behavior. While this report is to our knowledge the first to examine the acute effects of oxytocin in this population at high risk for violence and other forms of antisocial behavior, several limitations in the experimental design and the results cast the study as a preliminary report. Strategies for more extensive future projects are discussed.

Oxytocin attenuates aversive response to nicotine and anxiety-like behavior in adolescent rats.

PubMed

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.

Oxytocin makes females, but not males, less forgiving following betrayal of trust.

PubMed

Yao, Shuxia; Zhao, Weihua; Cheng, Rui; Geng, Yayuan; Luo, Lizhu; Kendrick, Keith M

2014-11-01

Although oxytocin has been shown to enhance trust behavior, to date no study has directly established whether oxytocin can modulate the effect of repair strategies on restoring damaged trust. In the current double-blind, between-subjects, placebo-controlled design study, two repair strategies were used to examine the effect of intranasal oxytocin administration on modulating trust restoration in a revised trust game. The results showed that although oxytocin had no overall effect on modulating trust restoration, it did have a significant gender specific effect. Female subjects showed less evidence for trust repair in the oxytocin compared with the placebo treatment group. This suggests that oxytocin may make female subjects exhibit more punitive behavior towards partners who violate their trust and less sensitive to repair strategies provided by them. Interestingly, this gender specific effect was more evident in the context of attempted trust repair using financial compensation. However, it also extended to both apology alone and no compensation conditions, but not to the fair one, in females exhibiting high trait forgiveness. Thus females with a more forgiving attitude towards betrayal may actually be more likely to punish betrayal following oxytocin treatment.

Oxytocin tempers calculated greed but not impulsive defense in predator–prey contests

PubMed Central

Scholte, H. Steven; van Winden, Frans A. A. M.; Ridderinkhof, K. Richard

2015-01-01

Human cooperation and competition is modulated by oxytocin, a hypothalamic neuropeptide that functions as both hormone and neurotransmitter. Oxytocin’s functions can be captured in two explanatory yet largely contradictory frameworks: the fear-dampening (FD) hypothesis that oxytocin has anxiolytic effects and reduces fear-motivated action; and the social approach/avoidance (SAA) hypothesis that oxytocin increases cooperative approach and facilitates protection against aversive stimuli and threat. We tested derivations from both frameworks in a novel predator–prey contest game. Healthy males given oxytocin or placebo invested as predator to win their prey’s endowment, or as prey to protect their endowment against predation. Neural activity was registered using 3T-MRI. In prey, (fear-motivated) investments were fast and conditioned on the amygdala. Inconsistent with FD, oxytocin did not modulate neural and behavioral responding in prey. In predators, (greed-motivated) investments were slower, and conditioned on the superior frontal gyrus (SFG). Consistent with SAA, oxytocin reduced predator investment, time to decide and activation in SFG. Thus, whereas oxytocin does not incapacitate the impulsive ability to protect and defend oneself, it lowers the greedy and more calculated appetite for coming out ahead. PMID:25140047

The Neuropeptide Oxytocin Induces a Social Altruism Bias.

PubMed

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 �

The two fold role of oxytocin in social developmental disorders: A cause and a remedy?

PubMed

Lefevre, Arthur; Sirigu, Angela

2016-04-01

Oxytocin is widely used by obstetricians to induce or facilitate labor. The long lasting consequences of oxytocin administration remain however unknown. Here, we discuss recent evidence suggesting a link between oxytocin labor induction and developmental social impairments such as autism spectrum disorders (ASD). Because these associations are methodologically questionable, we provide a review of animal studies investigating the long term effects of neonatal injection of oxytocin to shed light on the biological mechanisms that mediate the contribution of early oxytocin supplementation on the development of social impairments. In contrast to this potential negative impact on development, oxytocin has been shown to ameliorate social skills of ASD patients. However, results of chronic oxytocin administration from animal experiments are contradictory. We also review recent studies looking at chronic oxytocin effects in animal and in humans. Obstetric and psychiatric uses of exogenous oxytocin both impact on oxytocinergic neurotransmission but the effects may be sharply dissimilar. Copyright © 2016. Published by Elsevier Ltd.

Oxytocin, vasopressin, and autism: is there a connection?

PubMed

Insel, T R; O'Brien, D J; Leckman, J F

1999-01-15

Autism is a poorly understood developmental disorder characterized by social impairment, communication deficits, and compulsive behavior. The authors review evidence from animal studies demonstrating that the nonapeptides, oxytocin and vasopressin, have unique effects on the normal expression of species-typical social behavior, communication, and rituals. Based on this evidence, they hypothesize that an abnormality in oxytocin or vasopressin neurotransmission may account for several features of autism. As autism appears to be a genetic disorder, mutations in the various peptide, peptide receptor, or lineage-specific developmental genes could lead to altered oxytocin or vasopressin neurotransmission. Many of these genes have been cloned and sequenced, and several polymorphisms have been identified. Recent gene targeting studies that alter expression of either the peptides or their receptors in the rodent brain partially support the autism hypothesis. While previous experience suggests caution in hypothesizing a cause or suggesting a treatment for autism, the available preclinical evidence with oxytocin and vasopressin recommends the need for clinical studies using gene scanning, pharmacological and neurobiological approaches.

Advances in the role of oxytocin receptors in human parturition.

PubMed

Kim, Sung Hye; Bennett, Phillip R; Terzidou, Vasso

2017-07-05

Oxytocin (OT) is a neurohypophysial hormone which has been found to play a central role in the regulation of human parturition. The most established role of oxytocin/oxytocin receptor (OT/OTR) system in human parturition is the initiation of uterine contractions, however, recent evidence have demonstrated that it may have a more complex role including initiation of inflammation, regulation of miRNA expression, as well as mediation of other non-classical oxytocin actions via receptor crosstalk with other G protein-coupled receptors (GPCRs). In this review we highlight both established and newly emerging roles of OT/OTR system in human parturition and discuss the expanding potential for OTRs as pharmacological targets in the management of preterm labour. Copyright © 2017. Published by Elsevier B.V.

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

PubMed

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.

Oxytocin mediates early experience-dependent cross-modal plasticity in the sensory cortices.

PubMed

Zheng, Jing-Jing; Li, Shu-Jing; Zhang, Xiao-Di; Miao, Wan-Ying; Zhang, Dinghong; Yao, Haishan; Yu, Xiang

2014-03-01

Sensory experience is critical to development and plasticity of neural circuits. Here we report a new form of plasticity in neonatal mice, where early sensory experience cross-modally regulates development of all sensory cortices via oxytocin signaling. Unimodal sensory deprivation from birth through whisker deprivation or dark rearing reduced excitatory synaptic transmission in the correspondent sensory cortex and cross-modally in other sensory cortices. Sensory experience regulated synthesis and secretion of the neuropeptide oxytocin as well as its level in the cortex. Both in vivo oxytocin injection and increased sensory experience elevated excitatory synaptic transmission in multiple sensory cortices and significantly rescued the effects of sensory deprivation. Together, these results identify a new function for oxytocin in promoting cross-modal, experience-dependent cortical development. This link between sensory experience and oxytocin is particularly relevant to autism, where hypersensitivity or hyposensitivity to sensory inputs is prevalent and oxytocin is a hotly debated potential therapy.

The Peptide Oxytocin Antagonist F-792, When Given Systemically, Does Not Act Centrally in Lactating Rats.

PubMed

Leng, G; Russell, J A

2016-04-01

Oxytocin secreted by nerve terminals in the posterior pituitary has important actions for ensuring a successful outcome of pregnancy: it stimulates uterine contractions that lead to birth and it is essential in the milk-ejection reflex, enabling milk to be expelled from the mammary glands into the mouths of suckling young. Oxytocin also has important actions in the brain: released from dendrites of neurones that innervate the posterior pituitary, oxytocin auto-excites the neurones to fire action potentials in co-ordinated bursts, causing secretion of pulses of oxytocin. Central oxytocin actions are blocked by an oxytocin antagonist given into the brain and, consequently, milk transfer stops. Systemic peptide oxytocin antagonist (atosiban) treatment is used clinically in management of pre-term labour, a major obstetric problem. Hence, it is important to know whether an oxytocin antagonist given peripherally can enter the brain and interfere with central oxytocin actions. In the present study, we tested F792, a peptide oxytocin antagonist. In urethane-anaesthetised suckled rats, we show that the mammary gland responsiveness to oxytocin is blocked by i.v. injections of 7 μg/kg of F792, and the milk-ejection reflex is blocked when F792 is given directly into the brain at a dose of 0.2 μg. To critically test whether F792 given systemically can enter the brain, we recorded the suckling- and oxytocin-induced burst-firing of individual antidromically identified oxytocin neurones in the paraventricular nucleus. Given systemically at 100 μg/kg i.v., F792 acted only peripherally, blocking the milk-ejecting actions of oxytocin, but not the burst-firing of oxytocin neurones during suckling (n = 5 neurones in five rats). Hence, this peptide oxytocin antagonist does not enter the brain from the circulation to interfere with an essential oxytocin function in the brain. Furthermore, the functions of oxytocin in the brain evidently cannot be explored with a systemic peptide

Oxytocin and the biopsychology of performance in team sports.

PubMed

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.

Oxytocin and the Biopsychology of Performance in Team Sports

PubMed Central

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

Oxytocin Modulates Semantic Integration in Speech Comprehension.

PubMed

Ye, Zheng; Stolk, Arjen; Toni, Ivan; Hagoort, Peter

2017-02-01

Listeners interpret utterances by integrating information from multiple sources including word level semantics and world knowledge. When the semantics of an expression is inconsistent with their knowledge about the world, the listener may have to search through the conceptual space for alternative possible world scenarios that can make the expression more acceptable. Such cognitive exploration requires considerable computational resources and might depend on motivational factors. This study explores whether and how oxytocin, a neuropeptide known to influence social motivation by reducing social anxiety and enhancing affiliative tendencies, can modulate the integration of world knowledge and sentence meanings. The study used a between-participant double-blind randomized placebo-controlled design. Semantic integration, indexed with magnetoencephalography through the N400m marker, was quantified while 45 healthy male participants listened to sentences that were either congruent or incongruent with facts of the world, after receiving intranasally delivered oxytocin or placebo. Compared with congruent sentences, world knowledge incongruent sentences elicited a stronger N400m signal from the left inferior frontal and anterior temporal regions and medial pFC (the N400m effect) in the placebo group. Oxytocin administration significantly attenuated the N400m effect at both sensor and cortical source levels throughout the experiment, in a state-like manner. Additional electrophysiological markers suggest that the absence of the N400m effect in the oxytocin group is unlikely due to the lack of early sensory or semantic processing or a general downregulation of attention. These findings suggest that oxytocin drives listeners to resolve challenges of semantic integration, possibly by promoting the cognitive exploration of alternative possible world scenarios.

Generous to whom? The influence of oxytocin on social discounting.

PubMed

Pornpattananangkul, Narun; Zhang, Junfeng; Chen, Qiaoyu; Kok, Bing Cai; Yu, Rongjun

2017-05-01

Oxytocin is thought to play an essential role in pro-social behaviors, such as generosity and altruism, in humans. Yet, most research in humans that demonstrated the pro-social effect of oxytocin had participants interact with partners who were total strangers to them. In real life, however, people often interact with others varying in social relatedness with them (a concept known as social distance), ranging from their parents to total strangers. Here we employed the social-discounting framework to investigate whether the effect of oxytocin on prosociality depends on the social distance between the participants and their interaction partners. In a double-blind, placebo-controlled experiment (n=172 participants), we measured the amount of money participants were willing to forgo to another person as a function of social distance. We found that oxytocin administration selectively enhanced amount of money forgone toward total strangers, as opposed to someone closer to participants, suggesting that social distance constrained the pro-social effect of oxytocin. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effects of adjunctive intranasal oxytocin in patients with schizophrenia.

PubMed

Ota, Miho; Yoshida, Sumiko; Nakata, Masanori; Yada, Toshihiko; Kunugi, Hiroshi

2018-01-01

Both human and animal studies have suggested that oxytocin may have therapeutic potential in the treatment of schizophrenia. We evaluated the effects of intranasal oxytocin on cognition and its predictive factors in Japanese patients with schizophrenia. Subjects were 16 chronic schizophrenia patients who underwent intranasal oxytocin treatment for 3 months and were assessed for changes in severity of clinical symptoms and cognitions. Fifteen of the 16 subjects underwent 3-Tesla magnetic resonance imaging. Oxytocin significantly reduced scores on the positive and negative syndrome scale, especially on the negative symptoms. As for cognition, there was an improvement of the verbal fluency. Furthermore, the change of the negative score in positive and negative syndrome scale showed a negative correlation with the gray matter volumes of the right insula and left cingulate cortex. Our results indicate that daily administration of intranasal oxytocin may be effective for ameliorating clinical symptoms and cognitive functions in chronic schizophrenia patients, and this improvement may be related to the gray matter volume of the right insula and left cingulate cortex.

Supraoptic oxytocin and vasopressin neurons function as glucose and metabolic sensors

PubMed Central

Song, Zhilin; Levin, Barry E.; Stevens, Wanida

2014-01-01

Neurons in the supraoptic nuclei (SON) produce oxytocin and vasopressin and express insulin receptors (InsR) and glucokinase. Since oxytocin is an anorexigenic agent and glucokinase and InsR are hallmarks of cells that function as glucose and/or metabolic sensors, we evaluated the effect of glucose, insulin, and their downstream effector ATP-sensitive potassium (KATP) channels on calcium signaling in SON neurons and on oxytocin and vasopressin release from explants of the rat hypothalamo-neurohypophyseal system. We also evaluated the effect of blocking glucokinase and phosphatidylinositol 3 kinase (PI3K; mediates insulin-induced mobilization of glucose transporter, GLUT4) on responses to glucose and insulin. Glucose and insulin increased intracellular calcium ([Ca2+]i). The responses were glucokinase and PI3K dependent, respectively. Insulin and glucose alone increased vasopressin release (P < 0.002). Oxytocin release was increased by glucose in the presence of insulin. The oxytocin (OT) and vasopressin (VP) responses to insulin+glucose were blocked by the glucokinase inhibitor alloxan (4 mM; P ≤ 0.002) and the PI3K inhibitor wortmannin (50 nM; OT: P = 0.03; VP: P ≤ 0.002). Inactivating KATP channels with 200 nM glibenclamide increased oxytocin and vasopressin release (OT: P < 0.003; VP: P < 0.05). These results suggest that insulin activation of PI3K increases glucokinase-mediated ATP production inducing closure of KATP channels, opening of voltage-sensitive calcium channels, and stimulation of oxytocin and vasopressin release. The findings are consistent with SON oxytocin and vasopressin neurons functioning as glucose and “metabolic” sensors to participate in appetite regulation. PMID:24477542

Supraoptic oxytocin and vasopressin neurons function as glucose and metabolic sensors.

PubMed

Song, Zhilin; Levin, Barry E; Stevens, Wanida; Sladek, Celia D

2014-04-01

Neurons in the supraoptic nuclei (SON) produce oxytocin and vasopressin and express insulin receptors (InsR) and glucokinase. Since oxytocin is an anorexigenic agent and glucokinase and InsR are hallmarks of cells that function as glucose and/or metabolic sensors, we evaluated the effect of glucose, insulin, and their downstream effector ATP-sensitive potassium (KATP) channels on calcium signaling in SON neurons and on oxytocin and vasopressin release from explants of the rat hypothalamo-neurohypophyseal system. We also evaluated the effect of blocking glucokinase and phosphatidylinositol 3 kinase (PI3K; mediates insulin-induced mobilization of glucose transporter, GLUT4) on responses to glucose and insulin. Glucose and insulin increased intracellular calcium ([Ca(2+)]i). The responses were glucokinase and PI3K dependent, respectively. Insulin and glucose alone increased vasopressin release (P < 0.002). Oxytocin release was increased by glucose in the presence of insulin. The oxytocin (OT) and vasopressin (VP) responses to insulin+glucose were blocked by the glucokinase inhibitor alloxan (4 mM; P ≤ 0.002) and the PI3K inhibitor wortmannin (50 nM; OT: P = 0.03; VP: P ≤ 0.002). Inactivating K ATP channels with 200 nM glibenclamide increased oxytocin and vasopressin release (OT: P < 0.003; VP: P < 0.05). These results suggest that insulin activation of PI3K increases glucokinase-mediated ATP production inducing closure of K ATP channels, opening of voltage-sensitive calcium channels, and stimulation of oxytocin and vasopressin release. The findings are consistent with SON oxytocin and vasopressin neurons functioning as glucose and "metabolic" sensors to participate in appetite regulation.

Oxytocin, cortisol and 3,4-methylenedioxymethamphetamine: neurohormonal aspects of recreational 'ecstasy'.

PubMed

Parrott, Andrew C

2016-12-01

Most research into 3,4-methylenedioxymethamphetamine (MDMA) has debated its psychobiological effects in relation to neurotransmission. This article debates the contributory roles of the neurohormones oxytocin and cortisol for their psychobiological effects in humans. The empirical literature on these neurohormones is reviewed and suggestions for future research outlined. Acute MDMA or 'ecstasy' can generate increased levels of oxytocin and cortisol, and these neurohormonal changes may be important for its mood-enhancing and energy-activation effects in humans. However, an initial finding of enhanced sociability correlating with oxytocin levels has not been replicated. Potential reasons are debated. There may be dynamic interactions between the two neurohormones, with greater activation under cortisol, facilitating stronger positive feelings under oxytocin. Chronic regular use of MDMA can adversely affect cortisol in several ways. Regular users show increased cortisol in 3-month hair samples, changes to the cortisol awakening response, and indications of greater daily stress. Furthermore, these cortisol findings suggest changes to the hypothalamic-pituitary-adrenal axis. The effects of chronic MDMA usage on oxytocin still need to be investigated. It is concluded that the neurohormones oxytocin and cortisol contribute in various ways to the psychobiological effects of recreational ecstasy/MDMA.

The Neuropeptide Oxytocin Enhances Information Sharing and Group Decision Making Quality.

PubMed

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.

The Neuropeptide Oxytocin Enhances Information Sharing and Group Decision Making Quality

PubMed Central

De Wilde, Tim R. W.; Ten Velden, Femke S.; De Dreu, Carsten K. W.

2017-01-01

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. PMID:28074896

Oxytocin receptor gene variation predicts subjective responses to MDMA.

PubMed

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.

Oxytocin receptor gene variation predicts subjective responses to MDMA

PubMed Central

Bershad, Anya K.; Weafer, Jessica J.; Kirkpatrick, Matthew G.; Wardle, Margaret C.; Miller, Melissa A.; de Wit, Harriet

2016-01-01

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. PMID:26787430

Ventrolateral orbital cortex oxytocin attenuates neuropathic pain through periaqueductal gray opioid receptor.

PubMed

Taati, Mina; Tamaddonfard, Esmaeal

2018-06-01

Oxytocin plays an important role in supraspinal modulation of pain. In the present study, we investigated the effects of ventrolateral orbital cortex (VLOC) microinjection of oxytocin on neuropathic pain after blockade of opioid receptors in this area and ventrolateral periaqueductal gray (vlPAG). Neuropathic pain was induced by complete transcection of preoneal and tibial branches of sciatic nerve. The VLOC and vlPAG were unilaterally (contralateral to the sciatic nerve-injured side) and bilaterally implanted with guide cannulas, respectively. Mechanical paw withdrawal threshold (PWT) was measured using von Frey filaments. Area under curve (AUC) was also calculated. Microinjection of oxytocin (5, 10 and 20 ng/site) into the VLOC increased PWT. Antiallodynia induced by oxytocin (20 ng/site) was inhibited by prior intra-VLOC administration of atosiban (an oxytocin receptor antagonist, 100 ng/site) and naloxone (an opioid receptor antagonist, 500 ng/site). Prior microinjection of naloxone (500 ng/site) into the vlPAG also inhibited antiallodynia induced by intra-VLOC microinjection of oxytocin (20 ng/site). All the VLOC and vlPAG microinjected drugs did not alter locomotor activity. It is concluded that oxytocin and its receptor may be involved in modulation of neuropathic pain at the VLOC level. Opioid receptors of VLOC and vlPAG might be involved in the antiallodynic effect of the VLOC-microinjected oxytocin. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

High serum oxytocin is associated with metabolic syndrome in older men - The MINOS study.

PubMed

Szulc, Pawel; Amri, Ez Zoubir; Varennes, Annie; Panaia-Ferrari, Patricia; Fontas, Eric; Goudable, Joëlle; Chapurlat, Roland; Breuil, Véronique

2016-12-01

Oxytocin regulates food intake, carbohydrate and lipid metabolism, and urinary sodium excretion. We assessed the association between serum oxytocin levels and presence of metabolic syndrome (MetS) in older men. Cross-sectional study was performed in 540 volunteer men aged 50-85yrs from the MINOS cohort. Oxytocin was measured in fasting serum by radioimmunoassay (Oxytocin RIA, Phoenix Pharmaceuticals). MetS was diagnosed using the harmonized definition. Serum oxytocin was higher in 166 men with MetS vs. controls (p<0.005). After adjustment for confounders including leptin, higher oxytocin was associated with higher odds of MetS (OR=1.38 per SD, 95%CI: 1.10-1.71, p<0.005). Men with serum oxytocin >0.74pg/mL (median) had higher odds of MetS vs. men with oxytocin ⩽0.74pg/mL (OR=2.06, 95%CI: 1.33-3.18, p<0.005). Higher oxytocin levels and low testosterone levels (total or free) were significantly associated with higher odds of MetS jointly and independently of each other. Men having oxytocin >0.74pg/mL and total testosterone <300ng/dL (<10.4nmol/L) had higher odds of MetS vs. men without these characteristics (OR=3.95, 95%CI: 1.65-9.46, p<0.005). Men having 25-hydroxycholecalciferol levels <30ng/mL and oxytocin >0.74pg/mL had higher odds of MetS vs. men without these characteristics (OR=2.86, 95%CI: 1.47-5.58, p<0.01). Men having oxytocin >0.74pg/mL and osteocalcin levels <14.6ng/mL (lowest quartile) had higher odds of MetS vs. men without these characteristics (OR=4.12, 95%CI: 2.07-8.20, p<0.001). In older men, higher serum oxytocin levels are associated with higher odds of MetS regardless of potential confounders. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Oxytocin Receptor Gene Polymorphisms Are Associated with Human Directed Social Behavior in Dogs (Canis familiaris)

PubMed Central

Lakatos, Gabriella; Pergel, Enikő; Turcsán, Borbála; Pluijmakers, Jolanda; Vas, Judit; Elek, Zsuzsanna; Brúder, Ildikó; Földi, Levente; Sasvári-Székely, Mária; Miklósi, Ádám; Rónai, Zsolt; Kubinyi, Enikő

2014-01-01

The oxytocin system has a crucial role in human sociality; several results prove that polymorphisms of the oxytocin receptor gene are related to complex social behaviors in humans. Dogs' parallel evolution with humans and their adaptation to the human environment has made them a useful species to model human social interactions. Previous research indicates that dogs are eligible models for behavioral genetic research, as well. Based on these previous findings, our research investigated associations between human directed social behaviors and two newly described (−212AG, 19131AG) and one known (rs8679684) single nucleotide polymorphisms (SNPs) in the regulatory regions (5′ and 3′ UTR) of the oxytocin receptor gene in German Shepherd (N = 104) and Border Collie (N = 103) dogs. Dogs' behavior traits have been estimated in a newly developed test series consisting of five episodes: Greeting by a stranger, Separation from the owner, Problem solving, Threatening approach, Hiding of the owner. Buccal samples were collected and DNA was isolated using standard protocols. SNPs in the 3′ and 5′ UTR regions were analyzed by polymerase chain reaction based techniques followed by subsequent electrophoresis analysis. The gene–behavior association analysis suggests that oxytocin receptor gene polymorphisms have an impact in both breeds on (i) proximity seeking towards an unfamiliar person, as well as their owner, and on (ii) how friendly dogs behave towards strangers, although the mediating molecular regulatory mechanisms are yet unknown. Based on these results, we conclude that similarly to humans, the social behavior of dogs towards humans is influenced by the oxytocin system. PMID:24454713

Social evolution. Oxytocin-gaze positive loop and the coevolution of human-dog bonds.

PubMed

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.

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

PubMed

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.

Oxytocin and Cortisol Levels in Dog Owners and Their Dogs Are Associated with Behavioral Patterns: An Exploratory Study

PubMed Central

Petersson, Maria; Uvnäs-Moberg, Kerstin; Nilsson, Anne; Gustafson, Lise-Lotte; Hydbring-Sandberg, Eva; Handlin, Linda

2017-01-01

We have previously shown that dog–owner interaction results in increasing oxytocin levels in owners and dogs, decreasing cortisol levels in owners but increasing cortisol levels in dogs. The present study aimed to further investigate whether oxytocin and cortisol levels in the previously tested owners and dogs were associated with their behaviors during the interaction experiment. Ten female volunteer dog–owners and their male Labrador dogs participated in a 60 min interaction experiment with interaction taking place during 0–3 min and blood samples for analysis of oxytocin and cortisol were collected at 0, 1, 3, 5, 15, 30, and 60 min. The entire experiment was videotaped and the following variables were noted; the different types (stroking, scratching, patting and activating touch, i.e., scratching and patting combined) as well as the frequency of touch applied by the owner, the number of times the owner touched her dog, the dog’s positions and time spent in each position. Correlations were analyzed between the behavioral variables and basal oxytocin levels, maximum oxytocin levels, delta oxytocin levels, basal cortisol levels and cortisol levels at 15 min. Owners with low oxytocin levels before and during the interaction touched their dogs more frequently (0 min: Rs = -0.683, p = 0.042; oxytocin maximum: Rs = -0.783, p = 0.013). The lower the dogs’ oxytocin levels during the interaction, the more stroking they received (Rs = -0.717, p = 0.041). The more frequently activating touch was applied by the owner, the higher the dogs’ cortisol levels became (15 min: Rs = 0.661, p = 0.038). The higher the owners’ maximum oxytocin level the fewer position changes the dogs made (Rs = -0.817, p = 0.007) and the shorter time they spent sitting (Rs = -0.786, p = 0.036), whereas the higher the owners’ basal cortisol levels, the longer time the dogs spent standing (0 min: Rs = 0.683, p = 0.041). In conclusion, oxytocin and cortisol levels, both in dogs and in

Oxytocin and Cortisol Levels in Dog Owners and Their Dogs Are Associated with Behavioral Patterns: An Exploratory Study.

PubMed

Petersson, Maria; Uvnäs-Moberg, Kerstin; Nilsson, Anne; Gustafson, Lise-Lotte; Hydbring-Sandberg, Eva; Handlin, Linda

2017-01-01

We have previously shown that dog-owner interaction results in increasing oxytocin levels in owners and dogs, decreasing cortisol levels in owners but increasing cortisol levels in dogs. The present study aimed to further investigate whether oxytocin and cortisol levels in the previously tested owners and dogs were associated with their behaviors during the interaction experiment. Ten female volunteer dog-owners and their male Labrador dogs participated in a 60 min interaction experiment with interaction taking place during 0-3 min and blood samples for analysis of oxytocin and cortisol were collected at 0, 1, 3, 5, 15, 30, and 60 min. The entire experiment was videotaped and the following variables were noted; the different types (stroking, scratching, patting and activating touch, i.e., scratching and patting combined) as well as the frequency of touch applied by the owner, the number of times the owner touched her dog, the dog's positions and time spent in each position. Correlations were analyzed between the behavioral variables and basal oxytocin levels, maximum oxytocin levels, delta oxytocin levels, basal cortisol levels and cortisol levels at 15 min. Owners with low oxytocin levels before and during the interaction touched their dogs more frequently (0 min: R s = -0.683, p = 0.042; oxytocin maximum: R s = -0.783, p = 0.013). The lower the dogs' oxytocin levels during the interaction, the more stroking they received ( R s = -0.717, p = 0.041). The more frequently activating touch was applied by the owner, the higher the dogs' cortisol levels became (15 min: R s = 0.661, p = 0.038). The higher the owners' maximum oxytocin level the fewer position changes the dogs made ( R s = -0.817, p = 0.007) and the shorter time they spent sitting ( R s = -0.786, p = 0.036), whereas the higher the owners' basal cortisol levels, the longer time the dogs spent standing (0 min: R s = 0.683, p = 0.041). In conclusion, oxytocin and cortisol levels, both in dogs and in their

Gender differences in oxytocin-associated disruption of decision bias during emotion perception

PubMed Central

Lynn, Spencer K.; Hoge, Elizabeth A.; Fischer, Laura E.; Barrett, Lisa Feldman; Simon, Naomi M.

2014-01-01

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. PMID:24814142

A double-blind randomized controlled trial of oxytocin nasal spray in Prader Willi syndrome.

PubMed

Einfeld, Stewart L; Smith, Ellie; McGregor, Iain S; Steinbeck, Kate; Taffe, John; Rice, Lauren J; Horstead, Siân K; Rogers, Naomi; Hodge, M Antoinette; Guastella, Adam J

2014-09-01

Individuals with Prader-Willi syndrome (PWS) have a significant reduction in the number of oxytocin-producing neurons (42%) in the hypothalamic paraventricular nucleus. A number of animal studies and observations of humans show that lesions in this region can produce PWS-like symptoms. Given the evidence for potential oxytocin deficiency, we tested the effects of a course of intranasal oxytocin on PWS symptoms. Thirty individuals with PWS aged 12-30 years participated in an 18-week randomized double-blind placebo-controlled crossover trial. Participants received 8 weeks of oxytocin and 8 weeks of placebo with a minimum 2-week washout period. The first 11 participants received the following oxytocin doses: 24 IU (twice daily) B.I.D for participants 16 years and over and 18 IU B.I.D for participants 13-15 years. The dose was increased for the remaining 18 participants to 40 IU B.I.D for participants 16 years and over and 32 IU B.I.D for 13-15 years. Measures used to assess changes were standardized well-accepted measures, including the Developmental Behavior Checklist-Monitor, Parent, Teacher, and Adult; The Yale-Brown Obsessive Compulsive Scale; The Dykens Hyperphagia questionnaire; Reading The Mind in the Eyes Test; Epworth Sleepiness Scale and the Movie Stills. Oxytocin had little impact on any measure. The only significant difference found between the baseline, oxytocin, and placebo measures was an increase in temper outbursts (P = 0.023) with higher dose oxytocin. The lack of effect of oxytocin nasal spray may reflect the importance of endogenous release of oxytocin in response to exogenous oxytocin. © 2014 Wiley Periodicals, Inc.

Developmental Perspectives on Oxytocin and Vasopressin

PubMed Central

Hammock, Elizabeth A D

2015-01-01

The related neuropeptides oxytocin and vasopressin are involved in species-typical behavior, including social recognition behavior, maternal behavior, social bonding, communication, and aggression. A wealth of evidence from animal models demonstrates significant modulation of adult social behavior by both of these neuropeptides and their receptors. Over the last decade, there has been a flood of studies in humans also implicating a role for these neuropeptides in human social behavior. Despite popular assumptions that oxytocin is a molecule of social bonding in the infant brain, less mechanistic research emphasis has been placed on the potential role of these neuropeptides in the developmental emergence of the neural substrates of behavior. This review summarizes what is known and assumed about the developmental influence of these neuropeptides and outlines the important unanswered questions and testable hypotheses. There is tremendous translational need to understand the functions of these neuropeptides in mammalian experience-dependent development of the social brain. The activity of oxytocin and vasopressin during development should inform our understanding of individual, sex, and species differences in social behavior later in life. PMID:24863032

Association between prophylactic oxytocin use during dilation and evacuation and estimated blood loss.

PubMed

Whitehouse, Katherine; Tschann, Mary; Davis, James; Soon, Reni; Salcedo, Jennifer; Friedlander, EmmaKate; Kaneshiro, Bliss

2017-07-01

Some providers use oxytocin during dilation and evacuation (D&E) to prevent or treat hemorrhage, although evidence to support this is scarce. We sought to describe the association between prophylactic oxytocin use, estimated blood loss (EBL), and surgical outcomes during D&E. We performed a chart review of 730 women at 14 to 26 weeks' gestation who had a D&E at our institution between May 2010 and May 2014 to assess the association between prophylactic oxytocin use and EBL. We determined whether sociodemographic and health-related factors were associated with excessive blood loss (EBL≥250 mL) and whether oxytocin use was associated with complications, including hemorrhage (i.e., EBL≥500 mL or interventions for bleeding). We performed univariate analyses and multivariable regression models to evaluate the relationship between health-related factors and EBL≥250 mL. Providers used prophylactic oxytocin in 59.9% of procedures. Asian (p=.005 and Native Hawaiian/Pacific Islander (p=.005) race, nulliparity (p=.007) and higher gestational age (p<.001) were associated with prophylactic oxytocin use. We found no difference in mean EBL (116.2±105.5 mL versus 130.7±125.5 mL, p=.09), EBL≥250 mL (31.4% vs. 68.6%, p=.15) or complications (6.1% vs. 7.1%, p=.73) including hemorrhage (1.4% vs. 5.3%, p=.14) between those who did not receive prophylactic oxytocin and those who did. No transfusions occurred in either group. In multivariable regression modeling, the adjusted OR for excessive blood loss was 0.42 (95% confidence interval 0.16-1.07) with prophylactic oxytocin use. Prophylactic oxytocin use during D&E was not associated with hemorrhage or transfusion in our population. Routine use of interventions for bleeding, such as intravenous oxytocin, should be based on scientific evidence or not performed. Findings from our study provide information on how oxytocin use is associated with blood loss during D&E. Copyright © 2017 Elsevier Inc. All rights reserved.

Oxytocin administration suppresses hypothalamic activation in response to visual food cues.

PubMed

van der Klaauw, Agatha A; Ziauddeen, Hisham; Keogh, Julia M; Henning, Elana; Dachi, Sekesai; Fletcher, Paul C; Farooqi, I Sadaf

2017-06-27

The aim of this study was to use functional neuroimaging to investigate whether oxytocin modulates the neural response to visual food cues in brain regions involved in the control of food intake. Twenty-four normal weight volunteers received intranasal oxytocin (24 IU) or placebo in a double-blind, randomized crossover study. Measurements were made forty-five minutes after dosing. On two occasions, functional MRI (fMRI) scans were performed in the fasted state; the blood oxygen level-dependent (BOLD) response to images of high-calorie foods versus low-calorie foods was measured. Given its critical role in eating behaviour, the primary region of interest was the hypothalamus. Secondary analyses examined the parabrachial nuclei and other brain regions involved in food intake and food reward. Intranasal oxytocin administration suppressed hypothalamic activation to images of high-calorie compared to low-calorie food (P = 0.0125). There was also a trend towards suppression of activation in the parabrachial nucleus (P = 0.0683). No effects of intranasal oxytocin were seen in reward circuits or on ad libitum food intake. Further characterization of the effects of oxytocin on neural circuits in the hypothalamus is needed to establish the utility of targeting oxytocin signalling in obesity.

Oxytocin enhances pupil dilation and sensitivity to ‘hidden’ emotional expressions

PubMed Central

Wessberg, Johan; Ellingsen, Dan-Mikael; Chelnokova, Olga; Olausson, Håkan; Laeng, Bruno

2013-01-01

Sensing others’ emotions through subtle facial expressions is a highly important social skill. We investigated the effects of intranasal oxytocin treatment on the evaluation of explicit and ‘hidden’ emotional expressions and related the results to individual differences in sensitivity to others’ subtle expressions of anger and happiness. Forty healthy volunteers participated in this double-blind, placebo-controlled crossover study, which shows that a single dose of intranasal oxytocin (40 IU) enhanced or ‘sharpened’ evaluative processing of others’ positive and negative facial expression for both explicit and hidden emotional information. Our results point to mechanisms that could underpin oxytocin’s prosocial effects in humans. Importantly, individual differences in baseline emotional sensitivity predicted oxytocin’s effects on the ability to sense differences between faces with hidden emotional information. Participants with low emotional sensitivity showed greater oxytocin-induced improvement. These participants also showed larger task-related pupil dilation, suggesting that they also allocated the most attentional resources to the task. Overall, oxytocin treatment enhanced stimulus-induced pupil dilation, consistent with oxytocin enhancement of attention towards socially relevant stimuli. Since pupil dilation can be associated with increased attractiveness and approach behaviour, this effect could also represent a mechanism by which oxytocin increases human affiliation. PMID:22648957

Oxytocin effects on complex brain networks are moderated by experiences of maternal love withdrawal.

PubMed

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.

Self-soothing behaviors with particular reference to oxytocin release induced by non-noxious sensory stimulation.

PubMed

Uvnäs-Moberg, Kerstin; Handlin, Linda; Petersson, Maria

2014-01-01

Oxytocin, a hypothalamic nonapeptide, is linked to increased levels of social interaction, well-being and anti-stress effects. The effects of oxytocin that is released by sensory stimulation during different kinds of interactive behaviors are often underestimated or even forgotten. In fact, many of the positive effects caused during interaction, such a wellbeing, stress reduction and even health promotion, are indeed linked to oxytocin released in response to activation of various types of sensory nerves. Oxytocin is released in response to activation of sensory nerves during labor, breastfeeding and sexual activity. In addition oxytocin is released in response to low intensity stimulation of the skin, e.g., in response to touch, stroking, warm temperature, etc. Consequently oxytocin is not only released during interaction between mothers and infants, but also during positive interaction between adults or between humans and animals. Finally oxytocin is also released in response to suckling and food intake. Oxytocin released in the brain in response to sensory stimulation as a consequence of these types of interactive behaviors, contributes to every day wellbeing and ability to handle stress. Food intake or sex may be used or even abused to achieve oxytocin-linked wellbeing and stress relief to compensate for lack of good relationships or when the levels of anxiety are high. The present review article will summarize the role played by oxytocin released by sensory (in particular somatosensory) stimulation, during various kinds of interactive behaviors. Also the fact that the anti-stress effects of oxytocin are particularly strong when oxytocin is released in response to "low intensity" stimulation of the skin will be highlighted.

Self-soothing behaviors with particular reference to oxytocin release induced by non-noxious sensory stimulation

PubMed Central

Uvnäs-Moberg, Kerstin; Handlin, Linda; Petersson, Maria

2015-01-01

Oxytocin, a hypothalamic nonapeptide, is linked to increased levels of social interaction, well-being and anti-stress effects. The effects of oxytocin that is released by sensory stimulation during different kinds of interactive behaviors are often underestimated or even forgotten. In fact, many of the positive effects caused during interaction, such a wellbeing, stress reduction and even health promotion, are indeed linked to oxytocin released in response to activation of various types of sensory nerves. Oxytocin is released in response to activation of sensory nerves during labor, breastfeeding and sexual activity. In addition oxytocin is released in response to low intensity stimulation of the skin, e.g., in response to touch, stroking, warm temperature, etc. Consequently oxytocin is not only released during interaction between mothers and infants, but also during positive interaction between adults or between humans and animals. Finally oxytocin is also released in response to suckling and food intake. Oxytocin released in the brain in response to sensory stimulation as a consequence of these types of interactive behaviors, contributes to every day wellbeing and ability to handle stress. Food intake or sex may be used or even abused to achieve oxytocin-linked wellbeing and stress relief to compensate for lack of good relationships or when the levels of anxiety are high. The present review article will summarize the role played by oxytocin released by sensory (in particular somatosensory) stimulation, during various kinds of interactive behaviors. Also the fact that the anti-stress effects of oxytocin are particularly strong when oxytocin is released in response to “low intensity” stimulation of the skin will be highlighted. PMID:25628581

Arginine vasopressin and oxytocin modulate human social behavior.

PubMed

Ebstein, Richard P; Israel, Salomon; Lerer, Elad; Uzefovsky, Florina; Shalev, Idan; Gritsenko, Inga; Riebold, Mathias; Salomon, Shahaf; Yirmiya, Nurit

2009-06-01

Increasing evidence suggests that two nonapeptides, arginine vasopressin and oxytocin, shape human social behavior in both nonclinical and clinical subjects. Evidence is discussed that in autism spectrum disorders genetic polymorphisms in the vasopressin-oxytocin pathway, notably the arginine vasopressin receptor 1a (AVPR1a), the oxytocin receptor (OXTR), neurophysin I and II, and CD38 (recently shown to be critical for social behavior by mediating oxytocin secretion) contribute to deficits in socialization skills in this group of patients. We also present first evidence that CD38 expression in lymphoblastoid cells derived from subjects diagnosed with autism is correlated with social skill phenotype inventoried by the Vineland Adaptive Behavioral Scales. Additionally, we discuss molecular genetic evidence that in nonclinical subjects both AVPR1a and OXTR genes contribute to prosocial or altruistic behavior inventoried by two experimental paradigms, the dictator game and social values orientation. The role of the AVPR1a is also analyzed in prepulse inhibition. Prepulse inhibition of the startle response to auditory stimuli is a largely autonomic response that resonates with social cognition in both animal models and humans. First results are presented showing that intranasal administration of arginine vasopressin increases salivary cortisol levels in the Trier Social Stress test. To summarize, accumulating studies employing a broad array of cutting-edge tools in psychology, neuroeconomics, molecular genetics, pharmacology, electrophysiology, and brain imaging are beginning to elaborate the intriguing role of oxytocin and arginine vasopressin in human social behavior. We expect that future studies will continue this advance and deepen our understanding of these complex events.

Peripheral oxytocin suppresses food intake and causes weight loss in diet-induced obese rats

PubMed Central

Thatcher, Brendan S.; Reidelberger, Roger D.; Ogimoto, Kayoko; Wolden-Hanson, Tami; Baskin, Denis G.; Schwartz, Michael W.; Blevins, James E.

2012-01-01

Growing evidence suggests that oxytocin plays an important role in the regulation of energy balance and that central oxytocin administration induces weight loss in diet-induced obese (DIO) animals. To gain a better understanding of how oxytocin mediates these effects, we examined feeding and neuronal responses to oxytocin in animals rendered obese following exposure to either a high-fat (HFD) or low-fat diet (LFD). Our findings demonstrate that peripheral administration of oxytocin dose-dependently reduces food intake and body weight to a similar extent in rats maintained on either diet. Moreover, the effect of oxytocin to induce weight loss remained intact in leptin receptor-deficient Koletsky (fak/fak) rats relative to their lean littermates. To determine whether systemically administered oxytocin activates hindbrain areas that regulate meal size, we measured neuronal c-Fos induction in the nucleus of the solitary tract (NTS) and area postrema (AP). We observed a robust neuronal response to oxytocin in these hindbrain areas that was unexpectedly increased in rats rendered obese on a HFD relative to lean, LFD-fed controls. Finally, we report that repeated daily peripheral administration of oxytocin in DIO animals elicited a sustained reduction of food intake and body weight while preventing the reduction of energy expenditure characteristic of weight-reduced animals. These findings extend recent evidence suggesting that oxytocin circumvents leptin resistance and induces weight-loss in DIO animals through a mechanism involving activation of neurons in the NTS and AP, key hindbrain areas for processing satiety-related inputs. PMID:22008455

Plasma oxytocin changes and anti-obsessive response during serotonin reuptake inhibitor treatment: a placebo controlled study.

PubMed

Humble, Mats B; Uvnäs-Moberg, Kerstin; Engström, Ingemar; Bejerot, Susanne

2013-12-23

The drug treatments of choice for obsessive-compulsive disorder (OCD) are serotonin reuptake inhibitors (SRIs). However, a correlation between the neuropeptide oxytocin in cerebrospinal fluid and the severity of OCD has previously been shown, and oxytocin and serotonin are interconnected within the brain. Few studies have investigated whether SRIs have any effect on oxytocin; thus, our aim was to explore the possibility that oxytocinergic mechanisms contribute to the anti-obsessive effect of SRIs. In a randomized, double-blind trial, comparing SRIs (clomipramine and paroxetine) with placebo in 36 adults with OCD (characterized for subtypes), plasma oxytocin was measured with radioimmunoassay after plasma extraction, at baseline, after 1 week, and after 4 weeks of treatment, and related to baseline severity and clinical response after 12 weeks, as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Baseline oxytocin levels correlated positively with baseline Y-BOCS ratings, but only among the future SRI responders. Patients with early onset of OCD had higher baseline oxytocin. During treatment, plasma oxytocin did not differ between SRI and placebo treatment. In SRI responders, plasma oxytocin first decreased and then increased; in non-responders (to SRI as well as to placebo), the reverse was the case. After 4 weeks, treatment responders had attained higher oxytocin levels compared to non-responders. The intra-individual range (i.e., the variability) of plasma oxytocin between measurements was the measure that best differentiated responders from non-responders. This range was higher in responders than non-responders, and lower in patients with autistic traits. SRIs have highly variable effects on plasma oxytocin between individuals. The associations between baseline oxytocin and OCD severity and between oxytocin changes and treatment response support the notions that oxytocin is involved in OCD pathophysiology, and that the anti-obsessive effects of

Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism

PubMed Central

Peñagarikano, Olga; Lázaro, María T.; Lu, Xiao-Hong; Gordon, Aaron; Dong, Hongmei; Lam, Hoa A.; Peles, Elior; Maidment, Nigel T.; Murphy, Niall P.; Yang, X. William; Golshani, Peyman; Geschwind, Daniel H.

2015-01-01

Mouse models of neuropsychiatric diseases provide a platform for mechanistic understanding and development of new therapies. We previously demonstrated that knockout of the mouse homologue of CNTNAP2, in which mutant forms cause Cortical Dysplasia and Focal Epilepsy syndrome (CDFE), displays many features parallel to the human disorder. Since CDFE has high penetrance for autism spectrum disorder (ASD) we performed an in vivo screen for drugs that treat abnormal social behavior in Cntnap2 mutant mice and found that acute administration of the neuropeptide oxytocin improved social deficits. We found a decrease in the number of oxytocin immunoreactive neurons in the paraventricular nucleus (PVN) of the hypothalamus in mutant mice and an overall decrease in brain oxytocin levels. Administration of a selective melanocortin receptor 4 agonist, which causes endogenous oxytocin release, also acutely rescued the social deficits, an effect blocked by an oxytocin antagonist. We confirmed that oxytocin neurons mediated the behavioral improvement by activating endogenous oxytocin neurons in the paraventricular hypothalamus with Designer Receptors Exclusively Activated by Designer Drugs (DREADD). Last, we showed that chronic early postnatal treatment with oxytocin led to more lasting behavioral recovery and restored oxytocin immunoreactivity in the PVN. These data demonstrate dysregulation of the oxytocin system in Cntnap2 knockout mice and suggest that there may be critical developmental windows for optimal treatment. PMID:25609168

Fear or greed? Oxytocin regulates inter-individual conflict by enhancing fear in men.

PubMed

Zheng, Huimin; Kendrick, Keith M; Yu, Rongjun

2016-09-01

People may choose non-cooperation in social dilemmas either out of fear (if others choose to defect) or out of greed (when others choose to cooperate). Previous studies have shown that exogenous oxytocin motivates a "tend and defend" pattern in inter-group conflict in which oxytocin stimulates in-group cooperation and out-group defense. Using a double-blind placebo-controlled design combined with a modified Prisoner's dilemma game (PDG), we examined the effect of oxytocin on social motivations in inter-individual conflict in men. Results showed that compared with the placebo group, oxytocin-exposed participants were less cooperative in general. Specifically, oxytocin amplified the effect of fear on defection but did not influence the effect of greed. Another non-social control study confirmed participants' decisions were sensitive to social factors. Our findings suggest that even when social group conflict is removed, oxytocin promotes distrust of strangers in "me and you" inter-individual conflict by elevating social fear in men. Copyright © 2016 Elsevier Inc. All rights reserved.

[Oxytocin administration during spontaneous labour: Guidelines for clinical practice. Guidelines short text].

PubMed

Dupont, C; Carayol, M; Le Ray, C; Barasinski, C; Beranger, R; Burguet, A; Chantry, A; Chiesa, C; Coulm, B; Evrard, A; Fischer, C; Gaucher, L; Guillou, C; Leroy, F; Phan, E; Rousseau, A; Tessier, V; Vendittelli, F; Deneux-Tharaux, C; Riethmuller, D

2017-01-01

To define the different stages of spontaneous labour. To determine the indications, modalities of use and the effects of administering synthetic oxytocin. And to describe undesirable maternal and perinatal outcomes associated with the use of synthetic oxytocin. A systematic review was carried out by searching Medline database and websites of obstetrics learned societies until March 2016. The 1st stage of labor is divided in a latence phase and an active phase, which switch at 5cm of cervical dilatation. Rate of cervical dilatation is considered as abnormal below 1cm per 4hour during the first part of the active phase, and below 1cm per 2hours above 7cm of dilatation. During the latent phase of the first stage of labor, i.e. before 5cm of cervical dilatation, it is recommended that an amniotomy not be performed routinely and not to use oxytocin systematically. It is not recommended to expect the active phase of labor to start the epidural analgesia if patient requires it. If early epidural analgesia was performed, the administration of oxytocin must not be systematic. If dystocia during the active phase, an amniotomy is recommended in first-line treatment. In the absence of an improvement within an hour, oxytocin should be administrated. However, in the case of an extension of the second stage beyond 2hours, it is recommended to administer oxytocin to correct a lack of progress of the presentation. If dynamic dystocia, it is recommended to start initial doses of oxytocin at 2mUI/min, to respect at least 30min intervals between increases in oxytocin doses delivered, and to increase oxytocin doses by 2mUI/min intervals without surpassing a maximum IV flow rate of 20mUI/min. The reported maternal adverse effects concern uterine hyperstimulation, uterine rupture and post-partum haemorrhage, and those of neonatal adverse effects concern foetal heart rate anomalies associated with uterine hyperstimulation, neonatal morbidity and mortality, neonatal jaundice, weak suck

Oxytocin increases the influence of public service advertisements.

PubMed

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.

Oxytocin Increases the Influence of Public Service Advertisements

PubMed Central

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. PMID:23460821

Positive social behaviours are induced and retained after oxytocin manipulations mimicking endogenous concentrations in a wild mammal

PubMed Central

Twiss, Sean D.; Hazon, Neil; Moss, Simon; Pomeroy, Patrick P.

2017-01-01

The neuropeptide hormone oxytocin modulates numerous social and parental behaviours across a wide range of species, including humans. We conducted manipulation experiments on wild grey seals (Halichoerus grypus) to determine whether oxytocin increases proximity-seeking behaviour, which has previously been correlated with endogenous oxytocin concentrations in wild seal populations. Pairs of seals that had never met previously were given intravenous injections of 0.41 µg kg−1 oxytocin or saline and were observed for 1 h post-manipulation. The dose was designed to mimic endogenous oxytocin concentrations during the observation period, and is one of the lowest doses used to manipulate behaviour to date. Seals given oxytocin spent significantly more time in close proximity to each other, confirming that oxytocin causes conspecifics to seek others out and remain close to one another. Aggressive and investigative behaviours also significantly fell after oxytocin manipulations. Despite using a minimal oxytocin dose, pro-social behavioural changes unexpectedly persisted for 2 days despite rapid dose clearance from circulation post-injection. This study verifies that oxytocin promotes individuals staying together, demonstrating how the hormone can form positive feedback loops of oxytocin release following conspecific stimuli, increased motivation to remain in close proximity and additional oxytocin release from stimuli received while in close proximity. PMID:28539519

Positive social behaviours are induced and retained after oxytocin manipulations mimicking endogenous concentrations in a wild mammal.

PubMed

Robinson, Kelly J; Twiss, Sean D; Hazon, Neil; Moss, Simon; Pomeroy, Patrick P

2017-05-31

The neuropeptide hormone oxytocin modulates numerous social and parental behaviours across a wide range of species, including humans. We conducted manipulation experiments on wild grey seals ( Halichoerus grypus ) to determine whether oxytocin increases proximity-seeking behaviour, which has previously been correlated with endogenous oxytocin concentrations in wild seal populations. Pairs of seals that had never met previously were given intravenous injections of 0.41 µg kg -1 oxytocin or saline and were observed for 1 h post-manipulation. The dose was designed to mimic endogenous oxytocin concentrations during the observation period, and is one of the lowest doses used to manipulate behaviour to date. Seals given oxytocin spent significantly more time in close proximity to each other, confirming that oxytocin causes conspecifics to seek others out and remain close to one another. Aggressive and investigative behaviours also significantly fell after oxytocin manipulations. Despite using a minimal oxytocin dose, pro-social behavioural changes unexpectedly persisted for 2 days despite rapid dose clearance from circulation post-injection. This study verifies that oxytocin promotes individuals staying together, demonstrating how the hormone can form positive feedback loops of oxytocin release following conspecific stimuli, increased motivation to remain in close proximity and additional oxytocin release from stimuli received while in close proximity. © 2017 The Authors.

Oxytocin for preventing postpartum haemorrhage (PPH) in non-facility birth settings.

PubMed

Pantoja, Tomas; Abalos, Edgardo; Chapman, Evelina; Vera, Claudio; Serrano, Valentina P

2016-04-14

event. There were no cases of oxytocin use during labour.There were no data reported for some of this review's secondary outcomes: manual removal of placenta, maternal anaemia, neonatal death within 28 days, neonatal transfer to health facility for advanced care, breastfeeding rates. Similarly, the women's or the provider's satisfaction with the intervention was not reported. It is uncertain if oxytocin administered by CHO in non-facility settings compared with a control group reduces the incidence of severe PPH (>1000 mL), severe maternal morbidity or maternal deaths. However, the intervention probably decreases the incidence of PPH (> 500 mL).The quality of the one trial included in this review was limited because of the risk of attrition and recruitment biases related to limitations in the follow-up of pregnant women in both arms of the trials and some baseline imbalance on the size of babies at birth. Additionally, there was serious imprecision of the effect estimates for most of the primary outcomes mainly because of the size of the trial, very few or no events and CIs around both relative and absolute estimates of effect that include both appreciable benefit and appreciable harm.Although the trial presented data both for primary and secondary outcomes, it seemed to be underpowered to detect differences in the primary outcomes that are the ones more relevant for making judgments about the potential applicability of the intervention in other settings (especially severe PPH).Therefore, taking into account the extreme setting where the intervention was implemented, the limited role of the CHO in the trial and the lack of power for detecting effects on primary (relevant) outcomes, the applicability of the evidence found seems to be rather limited.Further well-executed and adequately-powered randomised controlled trials assessing the effects of using oxytocin in pre-filled injection devices or other new delivery systems (spray-dried ultrafine formulation of oxytocin) on

Oxytocin's neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: a randomized controlled trial.

PubMed

Aoki, Y; Watanabe, T; Abe, O; Kuwabara, H; Yahata, N; Takano, Y; Iwashiro, N; Natsubori, T; Takao, H; Kawakubo, Y; Kasai, K; Yamasue, H

2015-04-01

The neuropeptide oxytocin may be an effective therapeutic strategy for the currently untreatable social and communication deficits associated with autism. Our recent paper reported that oxytocin mitigated autistic behavioral deficits through the restoration of activity in the ventromedial prefrontal cortex (vmPFC), as demonstrated with functional magnetic resonance imaging (fMRI) during a socio-communication task. However, it is unknown whether oxytocin exhibited effects at the neuronal level, which was outside of the specific task examined. In the same randomized, double-blind, placebo-controlled, within-subject cross-over clinical trial in which a single dose of intranasal oxytocin (24 IU) was administered to 40 men with high-functioning autism spectrum disorder (UMIN000002241/000004393), we measured N-acetylaspartate (NAA) levels, a marker for neuronal energy demand, in the vmPFC using (1)H-magnetic resonance spectroscopy ((1)H-MRS). The differences in the NAA levels between the oxytocin and placebo sessions were associated with oxytocin-induced fMRI signal changes in the vmPFC. The oxytocin-induced increases in the fMRI signal could be predicted by the NAA differences between the oxytocin and placebo sessions (P=0.002), an effect that remained after controlling for variability in the time between the fMRI and (1)H-MRS scans (P=0.006) and the order of administration of oxytocin and placebo (P=0.001). Furthermore, path analysis showed that the NAA differences in the vmPFC triggered increases in the task-dependent fMRI signals in the vmPFC, which consequently led to improvements in the socio-communication difficulties associated with autism. The present study suggests that the beneficial effects of oxytocin are not limited to the autistic behavior elicited by our psychological task, but may generalize to other autistic behavioral problems associated with the vmPFC.

Oxytocin's neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: a randomized controlled trial

PubMed Central

Aoki, Y; Watanabe, T; Abe, O; Kuwabara, H; Yahata, N; Takano, Y; Iwashiro, N; Natsubori, T; Takao, H; Kawakubo, Y; Kasai, K; Yamasue, H

2015-01-01

The neuropeptide oxytocin may be an effective therapeutic strategy for the currently untreatable social and communication deficits associated with autism. Our recent paper reported that oxytocin mitigated autistic behavioral deficits through the restoration of activity in the ventromedial prefrontal cortex (vmPFC), as demonstrated with functional magnetic resonance imaging (fMRI) during a socio-communication task. However, it is unknown whether oxytocin exhibited effects at the neuronal level, which was outside of the specific task examined. In the same randomized, double-blind, placebo-controlled, within-subject cross-over clinical trial in which a single dose of intranasal oxytocin (24 IU) was administered to 40 men with high-functioning autism spectrum disorder (UMIN000002241/000004393), we measured N-acetylaspartate (NAA) levels, a marker for neuronal energy demand, in the vmPFC using 1H-magnetic resonance spectroscopy (1H-MRS). The differences in the NAA levels between the oxytocin and placebo sessions were associated with oxytocin-induced fMRI signal changes in the vmPFC. The oxytocin-induced increases in the fMRI signal could be predicted by the NAA differences between the oxytocin and placebo sessions (P=0.002), an effect that remained after controlling for variability in the time between the fMRI and 1H-MRS scans (P=0.006) and the order of administration of oxytocin and placebo (P=0.001). Furthermore, path analysis showed that the NAA differences in the vmPFC triggered increases in the task-dependent fMRI signals in the vmPFC, which consequently led to improvements in the socio-communication difficulties associated with autism. The present study suggests that the beneficial effects of oxytocin are not limited to the autistic behavior elicited by our psychological task, but may generalize to other autistic behavioral problems associated with the vmPFC. PMID:25070538

Oxytocin reversed MK-801-induced social interaction and aggression deficits in zebrafish.

PubMed

Zimmermann, Fernanda Francine; Gaspary, Karina Vidarte; Siebel, Anna Maria; Bonan, Carla Denise

2016-09-15

Changes in social behavior occur in several neuropsychiatric disorders such as schizophrenia and autism. The interaction between individuals is an essential aspect and an adaptive response of several species, among them the zebrafish. Oxytocin is a neuroendocrine hormone associated with social behavior. The aim of the present study was to investigate the effects of MK-801, a non-competitive antagonist of glutamate NMDA receptors, on social interaction and aggression in zebrafish. We also examined the modulation of those effects by oxytocin, the oxytocin receptor agonist carbetocin and the oxytocin receptor antagonist L-368,899. Our results showed that MK-801 induced a decrease in the time spent in the segment closest to the conspecific school and in the time spent in the segment nearest to the mirror image, suggesting an effect on social behavior. The treatment with oxytocin after the exposure to MK-801 was able to reestablish the time spent in the segment closest to the conspecific school, as well as the time spent in the segment nearest to the mirror image. In addition, in support of the role of the oxytocin pathway in modulating those responses, we showed that the oxytocin receptor agonist carbetocin reestablished the social and aggressive behavioral deficits induced by MK-801. However, the oxytocin receptor antagonist L-368,899 was not able to reverse the behavioral changes induced by MK-801. This study supports the critical role for NMDA receptors and the oxytocinergic system in the regulation of social behavior and aggression which may be relevant for the mechanisms associated to autism and schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

The Role of Oxytocin in Parenting and as Augmentative Pharmacotherapy: Critical Issues and Bold Conjectures.

PubMed

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

Plasma oxytocin immunoreactive products and response to trust in patients with social anxiety disorder.

PubMed

Hoge, Elizabeth A; Lawson, Elizabeth A; Metcalf, Christina A; Keshaviah, Aparna; Zak, Paul J; Pollack, Mark H; Simon, Naomi M

2012-11-01

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. 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. Mean oxytocin levels post-Trust Game (P = .025), and overall (area under the curve, P = .011) were lower in GSADpatients compared to controls, after controlling for sex and estradiol. There was no significant change in oxytocin levels after the game in either group. We report low plasma oxytocin levels in patients with GSAD during a prosocial laboratory task paradigm. Additional research will be important to further examine the relationship between oxytocin and social behavior in GSAD. © 2012 Wiley Periodicals, Inc.

In vivo somatostatin, vasopressin, and oxytocin synthesis in diabetic rat hypothalamus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fernstrom, J.D.; Fernstrom, M.H.; Kwok, R.P.

1990-04-01

The in vivo labeling of somatostatin-14, somatostatin-28, arginine vasopressin, and oxytocin was studied in rat hypothalamus after third ventricular administration of (35S)cysteine to streptozotocin-diabetic and normal rats. Immunoreactive somatostatin levels in hypothalamus were unaffected by diabetes, as was the incorporation of (35S)cysteine into hypothalamic somatostatin-14 and somatostatin-28. In contrast, immunoreactive vasopressin levels in hypothalamus and posterior pituitary (and oxytocin levels in posterior pituitary) were below normal in diabetic rats. Moreover, (35S)cysteine incorporation into hypothalamic vasopressin and oxytocin (probably mainly in the paraventricular nucleus because of its proximity to the third ventricular site of label injection) was significantly above normal. Themore » increments in vasopressin and oxytocin labeling were reversed by insulin administration. In vivo cysteine specific activity and the labeling of acid-precipitable protein did not differ between normal and diabetic animals; effects of diabetes on vasopressin and oxytocin labeling were therefore not caused by simple differences in cysteine specific activity. These results suggest that diabetes (1) does not influence the production of somatostatin peptides in hypothalamus but (2) stimulates the synthesis of vasopressin and oxytocin. For vasopressin at least, the increase in synthesis may be a compensatory response to the known increase in its secretion that occurs in uncontrolled diabetes.« less

Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism.

PubMed

Peñagarikano, Olga; Lázaro, María T; Lu, Xiao-Hong; Gordon, Aaron; Dong, Hongmei; Lam, Hoa A; Peles, Elior; Maidment, Nigel T; Murphy, Niall P; Yang, X William; Golshani, Peyman; Geschwind, Daniel H

2015-01-21

Mouse models of neuropsychiatric diseases provide a platform for mechanistic understanding and development of new therapies. We previously demonstrated that knockout of the mouse homolog of CNTNAP2 (contactin-associated protein-like 2), in which mutations cause cortical dysplasia and focal epilepsy (CDFE) syndrome, displays many features that parallel those of the human disorder. Because CDFE has high penetrance for autism spectrum disorder (ASD), we performed an in vivo screen for drugs that ameliorate abnormal social behavior in Cntnap2 mutant mice and found that acute administration of the neuropeptide oxytocin improved social deficits. We found a decrease in the number of oxytocin immunoreactive neurons in the paraventricular nucleus (PVN) of the hypothalamus in mutant mice and an overall decrease in brain oxytocin levels. Administration of a selective melanocortin receptor 4 agonist, which causes endogenous oxytocin release, also acutely rescued the social deficits, an effect blocked by an oxytocin antagonist. We confirmed that oxytocin neurons mediated the behavioral improvement by activating endogenous oxytocin neurons in the paraventricular hypothalamus with Designer Receptors Exclusively Activated by Designer Drugs (DREADD). Last, we showed that chronic early postnatal treatment with oxytocin led to more lasting behavioral recovery and restored oxytocin immunoreactivity in the PVN. These data demonstrate dysregulation of the oxytocin system in Cntnap2 knockout mice and suggest that there may be critical developmental windows for optimal treatment to rectify this deficit. Copyright © 2015, American Association for the Advancement of Science.

Oxytocin is not involved in luteolysis and early maternal recognition of pregnancy (MRP) in alpacas.

PubMed

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.

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

PubMed

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 (p<0.05). Higher oxytocin levels related to perceiving faces as happier in both female patients (r=-0.46, p=0.04) and controls (r=-0.40, p=0.04) but not in men. 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.

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

PubMed

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.

Separation Anxiety, Attachment and Inter-Personal Representations: Disentangling the Role of Oxytocin in the Perinatal Period

PubMed Central

Eapen, Valsamma; Dadds, Mark; Barnett, Bryanne; Kohlhoff, Jane; Khan, Feroza; Radom, Naomi; Silove, Derrick M.

2014-01-01

In this paper, we aimed to assess cross-sectionally and longitudinally associations between disturbances in maternal early attachment experiences, symptoms of separation anxiety and depression and oxytocin plasma levels. We examined a mediational model that tested the hypothesis that anxious attachment style arising from the mothers’ early bonding experiences with her own parents was associated with high levels of separation anxiety which, via its impact on depression, was associated with reduced levels of oxytocin in the postnatal period. Data is reported on a structured sample of 127 women recruited during pregnancy from a general hospital antenatal clinic and an initial follow up cohort of 57 women who were re-assessed at 3-months post-partum. We found an association between lower oxytocin level in the post partum period and symptoms of separation anxiety and depression during pregnancy, as well as maternal negative interpersonal representations, upbringing attributes and anxious attachment style. Further meditational analysis revealed that the unique association between anxious attachment and depression is mediated by separation anxiety and that depressed mood mediated the relationship between separation anxiety and oxytocin. In conjunction with evidence from the literature suggesting that lower oxytocin level is associated with bonding difficulties, our findings have significant implications for understanding the biological processes underpinning adverse attachment experiences, negative affect state, and mother-to-infant bonding difficulties. PMID:25229827

Separation anxiety, attachment and inter-personal representations: disentangling the role of oxytocin in the perinatal period.

PubMed

Eapen, Valsamma; Dadds, Mark; Barnett, Bryanne; Kohlhoff, Jane; Khan, Feroza; Radom, Naomi; Silove, Derrick M

2014-01-01

In this paper, we aimed to assess cross-sectionally and longitudinally associations between disturbances in maternal early attachment experiences, symptoms of separation anxiety and depression and oxytocin plasma levels. We examined a mediational model that tested the hypothesis that anxious attachment style arising from the mothers' early bonding experiences with her own parents was associated with high levels of separation anxiety which, via its impact on depression, was associated with reduced levels of oxytocin in the postnatal period. Data is reported on a structured sample of 127 women recruited during pregnancy from a general hospital antenatal clinic and an initial follow up cohort of 57 women who were re-assessed at 3-months post-partum. We found an association between lower oxytocin level in the post partum period and symptoms of separation anxiety and depression during pregnancy, as well as maternal negative interpersonal representations, upbringing attributes and anxious attachment style. Further meditational analysis revealed that the unique association between anxious attachment and depression is mediated by separation anxiety and that depressed mood mediated the relationship between separation anxiety and oxytocin. In conjunction with evidence from the literature suggesting that lower oxytocin level is associated with bonding difficulties, our findings have significant implications for understanding the biological processes underpinning adverse attachment experiences, negative affect state, and mother-to-infant bonding difficulties.

Intranasal oxytocin increases neural responses to social reward in post-traumatic stress disorder

PubMed Central

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

2017-01-01

Abstract Therapeutic alliance and perceived social support are important predictors of treatment response for post-traumatic stress disorder (PTSD). Intranasal oxytocin administration may enhance treatment response by increasing sensitivity for social reward and thereby therapeutic alliance and perceived social support. As a first step to investigate this therapeutical potential, we investigated whether intranasal oxytocin enhances neural sensitivity to social reward in PTSD patients. Male and female police officers with (n = 35) and without PTSD (n = 37) were included in a double-blind, randomized, placebo-controlled cross-over fMRI study. After intranasal oxytocin (40 IU) and placebo administration, a social incentive delay task was conducted to investigate neural responses during social reward and punishment anticipation and feedback. Under placebo, PTSD patients showed reduced left anterior insula (AI) responses to social rewards (i.e. happy faces) compared with controls. Oxytocin administration increased left AI responses during social reward in PTSD patients, such that PTSD patients no longer differed from controls under placebo. Furthermore, in PTSD patients, oxytocin increased responses to social reward in the right putamen. By normalizing abberant insula responses and increasing putamen responses to social reward, oxytocin administration may enhance sensitivity for social support and therapeutic alliance in PTSD patients. Future studies are needed to investigate clinical effects of oxytocin. PMID:27614769

Impact of intranasal oxytocin on interoceptive accuracy in alcohol users: an attentional mechanism?

PubMed Central

Gould Van Praag, Cassandra; Bond, Rod; Pfeifer, Gaby; Sequeira, Henrique; Duka, Theodora; Critchley, Hugo

2018-01-01

Abstract Interoception, i.e. the perception and appraisal of internal bodily signals, is related to the phenomenon of craving, and is reportedly disrupted in alcohol use disorders. The hormone oxytocin influences afferent transmission of bodily signals and, through its potential modulation of craving, is proposed as a possible treatment for alcohol use disorders. However, oxytocin’s impact on interoception in alcohol users remains unknown. Healthy alcohol users (n = 32) attended two laboratory sessions to perform tests of interoceptive ability (heartbeat tracking: attending to internal signals and, heartbeat discrimination: integrating internal and external signals) after intranasal administration of oxytocin or placebo. Effects of interoceptive accuracy, oxytocin administration and alcohol intake, were tested using mixed-effects models. On the tracking task, oxytocin reduced interoceptive accuracy, but did not interact with alcohol consumption. On the discrimination task, we found an interaction between oxytocin administration and alcohol intake: Oxytocin, compared with placebo, increased interoceptive accuracy in heavy drinkers, but not in light social drinkers. Our study does not suggest a pure interoceptive impairment in alcohol users but instead potentially highlights reduced flexibility of internal and external attentional resource allocation. Importantly, this impairment seems to be mitigated by oxytocin. This attentional hypothesis needs to be explicitly tested in future research. PMID:29618101

High-dose oxytocin is not associated with maternal temperature elevation: a retrospective cohort study of mid-trimester pregnancy with intrauterine fetal demise.

PubMed

Frölich, M A; Esame, A; Warren Iii, W M; Owen, J

2011-01-01

Maternal intrapartum fever has been associated with an increased incidence of neonatal morbidity. In this retrospective cohort study, we evaluated whether intravenous oxytocin has a fever-inducing effect. Oxytocin augments secretion of prostaglandins E(2) and F(2α) which are inflammatory mediators known to elevate body temperature. Between January 2005 and June 2008, 279 patients were admitted with mid-trimester fetal demise. Patients meeting inclusion criteria included 34 women who received a high-dose intravenous oxytocin regimen and 29 patients who delivered after spontaneous labor without the need for augmentation. Oral temperatures were measured on admission and at delivery. The median length of oxytocin infusion was 5.3h. The calculated temperature change was -0.14°C in the oxytocin group and +0.12°C in the control group. These findings were confirmed in a model adjusted for patients' white blood cell count and duration of labor. We did not observe an effect of analgesia type, epidural versus intravenous analgesia, on duration of labor. Based on this comparative analysis of pregnant women who received high-doses of oxytocin, we found insufficient evidence to support that high-dose intravenous oxytocin elevates intrapartum maternal temperature. Copyright © 2010 Elsevier Ltd. All rights reserved.

Plasma oxytocin changes and anti-obsessive response during serotonin reuptake inhibitor treatment: a placebo controlled study

PubMed Central

2013-01-01

Background The drug treatments of choice for obsessive-compulsive disorder (OCD) are serotonin reuptake inhibitors (SRIs). However, a correlation between the neuropeptide oxytocin in cerebrospinal fluid and the severity of OCD has previously been shown, and oxytocin and serotonin are interconnected within the brain. Few studies have investigated whether SRIs have any effect on oxytocin; thus, our aim was to explore the possibility that oxytocinergic mechanisms contribute to the anti-obsessive effect of SRIs. Method In a randomized, double-blind trial, comparing SRIs (clomipramine and paroxetine) with placebo in 36 adults with OCD (characterized for subtypes), plasma oxytocin was measured with radioimmunoassay after plasma extraction, at baseline, after 1 week, and after 4 weeks of treatment, and related to baseline severity and clinical response after 12 weeks, as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Results Baseline oxytocin levels correlated positively with baseline Y-BOCS ratings, but only among the future SRI responders. Patients with early onset of OCD had higher baseline oxytocin. During treatment, plasma oxytocin did not differ between SRI and placebo treatment. In SRI responders, plasma oxytocin first decreased and then increased; in non-responders (to SRI as well as to placebo), the reverse was the case. After 4 weeks, treatment responders had attained higher oxytocin levels compared to non-responders. The intra-individual range (i.e. the variability) of plasma oxytocin between measurements was the measure that best differentiated responders from non-responders. This range was higher in responders than non-responders, and lower in patients with autistic traits. Conclusions SRIs have highly variable effects on plasma oxytocin between individuals. The associations between baseline oxytocin and OCD severity and between oxytocin changes and treatment response support the notions that oxytocin is involved in OCD pathophysiology

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

PubMed

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.

The oxytocin receptor gene (OXTR) localizes to human chromosome 3p25 by fluorescence in situ hybridization and PCR analysis of somatic cell hybrids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simmons, C.F. Jr.; Clancy, T.E.; Quan, R.

1995-04-10

The human oxytocin receptor regulates parturition and myometrial contractility, breast milk let-down, and reproductive behaviors in the mammalian central nervous system. Kimura et al. recently identified a human oxytocin receptor cDNA by means of expression cloning from a human myometrial cDNA library. To elucidate further the molecular mechanisms that regulate oxytocin receptor gene expression and to define the expected Mendelian inheritance of possible human disease states, we must determine the number of genes, their localization, and their organization and structure. We summarize below our data indicating that the human oxytocin receptor gene is localized to 3p25 and exists as amore » single copy in the haploid genome. 9 refs., 2 figs.« less

Plasma Oxytocin Immunoreactive Products and Response to Trust in Patients with Social Anxiety Disorder

PubMed Central

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

The metabolic regulator PGC-1α directly controls the expression of the hypothalamic neuropeptide oxytocin.

PubMed

Blechman, Janna; Amir-Zilberstein, Liat; Gutnick, Amos; Ben-Dor, Shifra; Levkowitz, Gil

2011-10-19

The transcriptional coactivator PGC-1α is a key regulator of cellular energy expenditure in peripheral tissues. Recent studies report that PGC-1α-null mice develop late-onset obesity and that the neuronal inactivation of PGC-1α causes increased food intake. However, the exact role of PGC-1α in the CNS remains unclear. Here we show that PGC-1α directly regulates the expression of the hypothalamic neuropeptide oxytocin, a known central regulator of appetite. We developed a unique genetic approach in the zebrafish, allowing us to monitor and manipulate PGC-1α activity in oxytocinergic neurons. We found that PGC-1α is coexpressed with oxytocin in the zebrafish hypothalamus. Targeted knockdown of the zebrafish PGC-1α gene activity caused a marked decrease in oxytocin mRNA levels and inhibited the expression of a transgenic GFP reporter driven by the oxytocin promoter. The effect of PGC-1α loss of function on oxytocin gene activity was rescued by tissue-specific re-expression of either PGC-1α or oxytocin precursor in zebrafish oxytocinergic neurons. PGC-1α activated the oxytocin promoter in a heterologous cell culture system, and overexpression of PGC-1α induced ectopic expression of oxytocin in muscles and neurons. Finally, PGC-1α forms an in vivo complex with the oxytocin promoter in fed but not fasted animals. These findings demonstrate that PGC-1α is both necessary and sufficient for the production of oxytocin, implicating hypothalamic PGC-1α in the direct activation of a hypothalamic hormone known to control energy intake.

Pharmacoeconomic study comparing carbetocin with oxytocin for the prevention of hemorrhage following cesarean delivery in Lima, Peru.

PubMed

Caceda, Sonia Indacochea; Ramos, Richard Rubio; Saborido, Carlos Martín

2018-01-01

Postpartum hemorrhage is one of the main causes of maternal death. Oxytocin has traditionally been used to prevent postpartum hemorrhage. To compare oxytocin with carbetocin, a long-acting analog of oxytocin, for prevention of uterine hemorrhage after cesarean delivery. Clinical data were retrieved from the 2012 Cochrane meta-analysis "Carbetocin for preventing postpartum hemorrhage". A decision tree was constructed. The direct costs were those of medications from the Peruvian official price list (DIGEMID). Costs associated with additional oxytocic drugs, blood transfusions, postpartum hemorrhage kits and hysterectomy were obtained from Hospital Nacional Edgardo Rebagliati Martins. The perspective of the study was that of the payer. The time horizon for calculating quality-adjusted life years (QALYs) was 1 year (2015). Patients who received carbetocin required fewer additional uterotonic agents, had fewer hemorrhages and received fewer blood transfusions. Therefore, the costs associated with these interventions were lower. The incremental cost-effectiveness ratio was S/. 49,918 per QALY gained, which is lower than the threshold we estimated for Peru. Carbetocin is more cost-effective than oxytocin for prevention of uterine hemorrhage after cesarean delivery.

Judicious use of oxytocin augmentation for the management of prolonged labor.

PubMed

Rossen, Janne; Østborg, Tilde B; Lindtjørn, Elsa; Schulz, Jørn; Eggebø, Torbjørn M

2016-03-01

A protocol including judicious use of oxytocin augmentation was investigated to determine whether it would change how oxytocin was used and eventually influence labor and fetal outcomes. The population of this cohort study comprised 20 227 delivering women with singleton pregnancies ≥37 weeks, cephalic presentation, spontaneous or induced onset of labor, without previous cesarean section. Women delivering from 2009 to 2013 at Stavanger University Hospital, Norway, were included. Data were collected prospectively. Before implementing the protocol in 2010, oxytocin augmentation was used if progression of labor was perceived as slow. After implementation, oxytocin could only be started when the cervical dilation had crossed the 4-h action line in the partograph. The overall use of oxytocin augmentation was significantly reduced from 34.9% to 23.1% (p < 0.01). The overall frequency of emergency cesarean sections decreased from 6.9% to 5.3% (p < 0.05) and the frequency of emergency cesarean sections performed due to fetal distress was reduced from 3.2% to 2.0% (p = 0.01). The rate of women with duration of labor over 12 h increased from 4.4% to 8.5% (p < 0.01) and more women experienced severe estimated postpartum hemorrhage (2.6% vs. 3.7%; p = 0.01). The frequency of children with pH <7.1 in the umbilical artery was reduced from 4.7% to 3.2% (p < 0.01). The frequency of emergency cesarean section was reduced after implementing judicious use of oxytocin augmentation. Our findings may be of interest in the ongoing discussion of how the balanced use of oxytocin for labor augmentation can best be achieved. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

Maternal Oxytocin Administration Before Birth Influences the Effects of Birth Anoxia on the Neonatal Rat Brain.

PubMed

Boksa, Patricia; Zhang, Ying; Nouel, Dominique

2015-08-01

Ineffective contractions and prolonged labor are common birth complications in primiparous women, and oxytocin is the most common agent given for induction or augmentation of labor. Clinical studies in humans suggest oxytocin might adversely affect the CNS response to hypoxia at birth. In this study, we used a rat model of global anoxia during Cesarean section birth to test if administering oxytocin to pregnant dams prior to birth affects the acute neonatal CNS response to birth anoxia. Anoxic pups born from dams pre-treated with intravenous injections or infusions of oxytocin before birth showed significantly increased brain lactate, a metabolic indicator of CNS hypoxia, compared to anoxic pups from dams pre-treated with saline. Anoxic pups born from dams given oxytocin before birth also showed decreased brain ATP compared to anoxic pups from saline dams. Direct injection of oxytocin to postnatal day 2 rat pups followed by exposure to anoxia also resulted in increased brain lactate and decreased brain ATP, compared to anoxia exposure alone. Oxytocin pre-treatment of the dam decreased brain malondialdehyde, a marker of lipid peroxidation, as well as protein kinase C activity, both in anoxic pups and controls, suggesting oxytocin may reduce aspects of oxidative stress. Finally, when dams were pretreated with indomethacin, a cyclooxygenase (COX) inhibitor, maternal oxytocin no longer potentiated effects of anoxia on neonatal brain lactate, suggesting this effect of oxytocin may be mediated via prostaglandin production or other COX-derived products. The results indicate that maternal oxytocin administration may have multiple acute effects on CNS metabolic responses to anoxia at birth.

Involvement of Prolactin-Releasing Peptide in the Activation of Oxytocin Neurones in Response to Food Intake

PubMed Central

Yamashita, M; Takayanagi, Y; Yoshida, M; Nishimori, K; Kusama, M; Onaka, T

2013-01-01

Food intake activates neurones expressing prolactin-releasing peptide (PrRP) in the medulla oblongata and oxytocin neurones in the hypothalamus. Both PrRP and oxytocin have been shown to have an anorexic action. In the present study, we investigated whether the activation of oxytocin neurones following food intake is mediated by PrRP. We first examined the expression of PrRP receptors (also known as GPR10) in rats. Immunoreactivity of PrRP receptors was observed in oxytocin neurones and in vasopressin neurones in the paraventricular and supraoptic nuclei of the hypothalamus and in the bed nucleus of the stria terminalis. Application of PrRP to isolated supraoptic nuclei facilitated the release of oxytocin and vasopressin. In mice, re-feeding increased the expression of Fos protein in oxytocin neurones of the hypothalamus and bed nucleus of the stria terminalis. The increased expression of Fos protein in oxytocin neurones following re-feeding or i.p. administration of cholecystokinin octapeptide (CCK), a peripheral satiety factor, was impaired in PrRP-deficient mice. CCK-induced oxytocin increase in plasma was also impaired in PrRP-deficient mice. Furthermore, oxytocin receptor-deficient mice showed an increased meal size, as reported in PrRP-deficient mice and in CCKA receptor-deficient mice. These findings suggest that PrRP mediates, at least in part, the activation of oxytocin neurones in response to food intake, and that the CCK–PrRP–oxytocin pathway plays an important role in the control of the termination of each meal. PMID:23363338

Sublingual misoprostol versus intravenous oxytocin in prevention of post-partum hemorrhage.

PubMed

Tewatia, Renu; Rani, Shikha; Srivastav, Usha; Makhija, Bela

2014-04-01

Post-partum hemorrhage (PPH) is the most common direct cause of maternal mortality and timely intervention can save many lives. To compare the effectiveness of sublingual misoprostol to intravenous oxytocin in preventing post-partum hemorrhage in low risk vaginal birth. One hundred patients with no risk factor for PPH were randomly allocated to receive 600 μg misoprostol administered sublingually or 10 IU of intravenous oxytocin immediately after the delivery of baby. Main outcome measures were post-partum blood loss, drop in hemoglobin in 24 h, duration of third stage of labor, and drug-related adverse effects. Mean age, parity and gestational age were similar in both groups. Mean blood loss was significantly lower in oxytocin group (114.28 ± 26.75 versus 149.50 ± 30.78 ml; p = 0.00). Drop in hemoglobin was 0.31 ± 0.16 versus 0.49 ± 0.21 g% (p = 0.01) in oxytocin and misoprostol group, respectively. Duration of third stage labor was shorter in oxytocin group (median 5 min, IQR: 4.5-5.5 versus 5.5 min, IQR: 5-6 min, p < 0.01). Although fever and shivering were common adverse effects with misoprostol but were not clinically significant. Intravenous oxytocin is more efficacious than sublingual misoprostol in preventing PPH in institutional deliveries.

Intranasal oxytocin increases neural responses to social reward in post-traumatic stress disorder.

PubMed

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

2017-02-01

Therapeutic alliance and perceived social support are important predictors of treatment response for post-traumatic stress disorder (PTSD). Intranasal oxytocin administration may enhance treatment response by increasing sensitivity for social reward and thereby therapeutic alliance and perceived social support. As a first step to investigate this therapeutical potential, we investigated whether intranasal oxytocin enhances neural sensitivity to social reward in PTSD patients. Male and female police officers with (n = 35) and without PTSD (n = 37) were included in a double-blind, randomized, placebo-controlled cross-over fMRI study. After intranasal oxytocin (40 IU) and placebo administration, a social incentive delay task was conducted to investigate neural responses during social reward and punishment anticipation and feedback. Under placebo, PTSD patients showed reduced left anterior insula (AI) responses to social rewards (i.e. happy faces) compared with controls. Oxytocin administration increased left AI responses during social reward in PTSD patients, such that PTSD patients no longer differed from controls under placebo. Furthermore, in PTSD patients, oxytocin increased responses to social reward in the right putamen. By normalizing abberant insula responses and increasing putamen responses to social reward, oxytocin administration may enhance sensitivity for social support and therapeutic alliance in PTSD patients. Future studies are needed to investigate clinical effects of oxytocin. © The Author (2016). Published by Oxford University Press.

Administration of an oxytocin receptor antagonist attenuates sexual motivation in male rats.

PubMed

Blitzer, D S; Wells, T E; Hawley, W R

2017-08-01

In male rats, oxytocin impacts both sexual arousal and certain types of consummatory sexual behaviors. However, the role of oxytocin in the motivational aspects of sexual behavior has received limited attention. Given the role that oxytocin signaling plays in consummatory sexual behaviors, it was hypothesized that pharmacological attenuation of oxytocin signaling would reduce sexual motivation in male rats. Sexually experienced Long-Evans male rats were administered either an oxytocin receptor antagonist (L368,899 hydrochloride; 1mg/kg) or vehicle control into the intraperitoneal cavity 40min prior to placement into the center chamber of a three-chambered arena designed to assess sexual motivation. During the 20-minute test, a sexually experienced stimulus male rat and a sexually receptive stimulus female rat were separately confined to smaller chambers that were attached to the larger end chambers of the arena. However, physical contact between test and stimulus rats was prevented by perforated dividers. Immediately following the sexual motivation test, test male rats were placed with a sexually receptive female to examine consummatory sexual behaviors. Although both drug and vehicle treated rats exhibited a preference for the female, treatment with an oxytocin receptor antagonist decreased the amount of time spent with the female. There were no differences between drug and vehicle treated rats in either general activity, exploratory behaviors, the amount of time spent near the stimulus male rat, or consummatory sexual behaviors. Extending previous findings, these results indicate that oxytocin receptors are involved in sexual motivation in male rats. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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.

Umbilical vein oxytocin for the treatment of retained placenta (Release Study): a double-blind, randomised controlled trial.

PubMed

Weeks, Andrew D; Alia, Godfrey; Vernon, Gillian; Namayanja, Annette; Gosakan, Radhika; Majeed, Tayyaba; Hart, Anna; Jafri, Hussain; Nardin, Juan; Carroli, Guillermo; Fairlie, Fiona; Raashid, Yasmin; Mirembe, Florence; Alfirevic, Zarko

2010-01-09

Retained placenta is associated with post-partum haemorrhage. Meta-analysis has suggested that umbilical injection of oxytocin could increase placental expulsion without the need for a surgeon or anaesthetic. We assessed the effect of high-dose umbilical vein oxytocin as a treatment for retained placenta. In this double-blind, placebo-controlled trial, haemodynamically stable women with a retained placenta for more than 30 min were recruited from 13 sites in the UK, Uganda, and Pakistan. 577 women were randomly assigned by a computer-generated randomisation list stratified by centre to 30 mL saline containing either 50 IU oxytocin (n=292) or 5 mL water (n=285), which was injected into the placenta through an umbilical vein catheter. All trial participants, study workers, and data handlers were masked to individual allocations. The primary outcome was the need for manual removal of the placenta. Analysis was by intention to treat. This study is registered, number ISRCTN 13204258. The primary outcome was recorded for all participants. We detected no difference between the groups in the need for manual removal of placenta (oxytocin 179/292 [61.3%] vs placebo 177/285 [62.1%]; relative risk 0.98, 95% CI 0.87-1.12; p=0.84). The need for manual removal was higher in the UK (overall 250/361 [69%]) than in Uganda (90/190 [47%]) or Pakistan (16/26 [62%]). Adverse events did not differ between the two groups. Umbilical oxytocin has no clinically significant effect on the need for manual removal for women with retained placenta. WHO, WellBeing of Women, Pakistan Higher Education Commission. Copyright 2010 Elsevier Ltd. All rights reserved.

Effects of early augmentation of labour with amniotomy and oxytocin in nulliparous women: a meta-analysis.

PubMed

Fraser, W; Vendittelli, F; Krauss, I; Bréart, G

1998-02-01

To estimate the effects among nulliparae of early augmentation with amniotomy and oxytocin on caesarean delivery, and on other indicators of maternal and neonatal morbidity including transfusion. Apgar score < 7 at 5 minutes, and admission to the special care nursery. Meta-analysis. Published studies were identified through manual and computerised searches. Two unpublished studies were identified through direct communication with the investigators. Twelve trials were identified which compared a policy of early labour augmentation including amniotomy followed by oxytocin with a less active form of management. Two methodologically unacceptable studies were excluded. Studies were grouped according to whether they admitted only women with abnormal progress (therapy trials: n = 3) or accepted women with normal labour (prevention trials: n = 7). Unstratified analysis did not provide support for the hypothesis that early augmentation reduces the risk of caesarean section (typical odds ratio [OR] 0.9; 95% CI 0.7-1.1). The typical odds ratio for prevention trials was similar to that obtained in the unstratified analysis (typical OR 0.9, 95% CI 0.7-1.2). Although only a small number of women have been randomised in therapy trials, a trend toward a reduction in the rate of caesarean section with early intervention was seen in this group (typical OR 0.6, 95% CI 0.2-1.4). Early augmentation does not appear to provide benefit over a more conservative form of management in the context of care of nulliparous women with mild delays in the progress of labour. In the context of established delay in labour, an active policy of augmentation may reduce the risk of caesarean section. However, only three small trials have been performed in this context, and they do not have adequate power to allow firm conclusions to be drawn.

Development of a highly specific enzyme immunoassay for oxytocin and its use in plasma samples.

PubMed

Haraya, Shiomi; Karasawa, Koji; Sano, Yoshihiro; Ozawa, Kimiko; Kato, Nobumasa; Arakawa, Hidetoshi

2017-01-01

Background The peptide hormone oxytocin acts in the central nervous system and plays an important role in various complex social behaviours. We report the production of a high affinity and specificity antibody for oxytocin and its use in a highly sensitive enzyme immunoassay. Biotin that was chemically bound to oxytocin derivative containing zero to six lysines as bridge was the labelled antigen. Seven labelled antigens were used to develop a highly sensitive enzyme immunoassay. Methods Antioxytocin antiserum was obtained by immunization of oxytocin-bovine thyrogloblin conjugate to rabbit. Oxytocin sample was added to the second antibody-coated microtitre plate and allowed to react overnight at 4℃, then biotinylated oxytocin was added 1 h at 4℃, and horseradish peroxidase-labelled avidin was added and incubated for 1 h at room temperature. The plate was then washed. Horseradish peroxidase activity was measured by a colorimetric method using o-phenylenediamine (490 nm). Results The sensitivity of the enzyme immunoassay improved as the number of lysine residues increased; consequently, biotinylated oxytocin bridged with five lysines was used. A standard curve for oxytocin ranged from 1.0 to 1000 pg/assay. The detection limit of the assay was 2.36 pg, and the reproducibility was 3.6% as CV% ( n = 6). Cross-reactivity with vasopressin and vasotocin was less than 0.01%. Conclusion The sensitivity of the enzyme immunoassay could be improved by increasing the number of lysine residues on the biotin-labelled antigen. The proposed method is sensitive and more specific than conventional immunoassays for oxytocin and can be used to determine plasma oxytocin concentrations.

Intranasal administration of oxytocin increases envy and schadenfreude (gloating).

PubMed

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.

Relationship between dietary intake and behaviors with oxytocin: a systematic review of studies in adults.

PubMed

Skinner, Janelle A; Garg, Manohar L; Dayas, Christopher V; Fenton, Sasha; Burrows, Tracy L

2018-05-01

Oxytocin plays an important hormonal role in the regulation of feeding and energy intake. The aims of this review were to 1) determine the effects of dietary intake/behaviors on endogenous oxytocin and 2) examine the effect of exogenous oxytocin on dietary intake/behaviors. Published studies up to December 2016 were identified through searches of 5 electronic databases. Eligible studies included those in adults that included a measure related to an individual's diet and a measure of oxytocin and the relationship between the 2 outcomes. Twenty-six studies (n = 912 participants; 77% female) were included. The most common dietary outcomes assessed were alcohol, caffeine, calcium, sodium, fat, and calorie intake. It was found that endogenous oxytocin (n = 13) in nonclinical samples did not change significantly (P > 0.05) through altered diet or behaviors (neutral effect); in contrast, significant (P < 0.05) differences (increases and decreases) were identified in clinical samples. Exogenous oxytocin studies (n = 13) found reduced indices of food intake (positive effect) in clinical and nonclinical samples. Overall, few studies included comprehensive investigation of dietary intakes through the use of validated assessment tools. Dietary intake and behaviors appear to have some influence on oxytocin, with more pronounced effects found with exogenously administered oxytocin.

DNA damage after chronic oxytocin administration in rats: a safety yellow light?

PubMed

Leffa, Daniela D; Daumann, Francine; Damiani, Adriani P; Afonso, Arlindo C; Santos, Maria A; Pedro, Thayara H; Souza, Renan P; Andrade, Vanessa M

2017-02-01

Adjuvant therapy is a common therapeutic strategy used for schizophrenia management. Oxytocin has shown promising results as antipsychotic adjuvant in patients with schizophrenia. Although short-term clinical studies have indicated tolerability and no major side-effect manifestation, long-term studies remain needed. In this study, we investigated whether oxytocin chronic administration in rats may lead to brain DNA damage by comet assay. Our results suggest that 21 and 56-day treatment with once daily intraperitoneal oxytocin (0.1, 1.0 and 10.0 mg/kg) may cause substantial DNA damage in hippocampus. We have not found differences on body weight gain. Our findings also point that further clinical and preclinical studies evaluating oxytocin safety after chronic exposure are necessary.

[Oxytocin, a mediator of anti-stress, well-being, social interaction, growth and healing].

PubMed

Uvnas-Moberg, Kerstin; Petersson, Maria

2005-01-01

The neuroendocrine and physiological systems related to pain and stress have long been subjected to study. More recently, the corresponding systems promoting anti-stress and restoration have also come into focus. It is not only important to investigate the mechanisms underlying disease but also to examine the physiological and psychological mechanisms which protect and heal the body and soul. The nonapeptide oxytocin, originally known to stimulate labour and milk ejection, appears to play an important role in this regard. Oxytocin can induce anti-stress-like effects such as reduction of blood pressure and cortisol levels. It increases pain thresholds, exerts an anxiolytic-like effect and stimulates various types of positive social interaction. In addition, it promotes growth and healing. Repeated exposure to oxytocin causes long-lasting effects by influencing the activity of other transmitter systems, a pattern which makes oxytocin potentially clinically relevant. Oxytocin can be released by various types of non-noxious sensory stimulation, for example by touch and warmth. Ingestion of food triggers oxytocin release by activation of vagal afferents. Most likely, oxytocin can also be released by stimulation of other senses such as olfaction, as well as by certain types of sound and light. In addition, purely psychological mechanisms may trigger the release of oxytocin. This means that positive interaction involving touch and psychological support may be health-promoting. The social interaction of daily life, as well as a positive environment, continuously activate this system. In addition, various types of psychotherapy involving transfer of support, warmth and empathy are likely to induce similar effects, which thus contribute to the positive effects of these kinds of therapies.

The association of single-nucleotide polymorphisms in the oxytocin receptor and G protein-coupled receptor kinase 6 (GRK6) genes with oxytocin dosing requirements and labor outcomes.

PubMed

Grotegut, Chad A; Ngan, Emily; Garrett, Melanie E; Miranda, Marie Lynn; Ashley-Koch, Allison E; Swamy, Geeta K

2017-09-01

Oxytocin is a potent uterotonic agent that is widely used for induction and augmentation of labor. Oxytocin has a narrow therapeutic index and the optimal dosing for any individual woman varies widely. The objective of this study was to determine whether genetic variation in the oxytocin receptor (OXTR) or in the gene encoding G protein-coupled receptor kinase 6 (GRK6), which regulates desensitization of the oxytocin receptor, could explain variation in oxytocin dosing and labor outcomes among women being induced near term. Pregnant women with a singleton gestation residing in Durham County, NC, were prospectively enrolled as part of the Healthy Pregnancy, Healthy Baby cohort study. Those women undergoing an induction of labor at 36 weeks or greater were genotyped for 18 haplotype-tagging single-nucleotide polymorphisms in OXTR and 7 haplotype-tagging single-nucleotide polymorphisms in GRK6 using TaqMan assays. Linear regression was used to examine the relationship between maternal genotype and maximal oxytocin infusion rate, total oxytocin dose received, and duration of labor. Logistic regression was used to test for the association of maternal genotype with mode of delivery. For each outcome, backward selection techniques were utilized to control for important confounding variables and additive genetic models were used. Race/ethnicity was included in all models because of differences in allele frequencies across populations, and Bonferroni correction for multiple testing was used. DNA was available from 482 women undergoing induction of labor at 36 weeks or greater. Eighteen haplotype-tagging single-nucleotide polymorphisms within OXTR and 7 haplotype-tagging single-nucleotide polymorphisms within GRK6 were examined. Five single-nucleotide polymorphisms in OXTR showed nominal significance with maximal infusion rate of oxytocin, and two single-nucleotide polymorphisms in OXTR were associated with total oxytocin dose received. One single-nucleotide polymorphism in

Oxytocin and social context moderate social support seeking in women during negative memory recall.

PubMed

Cardoso, Christopher; Valkanas, Helen; Serravalle, Lisa; Ellenbogen, Mark A

2016-08-01

Oxytocin is theorized to promote social support seeking under stress- an alternate biobehavioural response to challenge known as the tend-and-befriend response. These effects may be context dependent, however, and no study has evaluated this effect in the presence and absence of social support. The aim of this study was to evaluate the effects of oxytocin on the experience of recalling emotional autobiographical memories in two contexts-with and without social contact with an experimenter. Sixty-three individuals (32 female) participated in this randomized, double-blind, placebo-controlled, and within-subject study. During recall of negative memories in the absence of social contact, oxytocin decreased perceived emotional support relative to placebo F(1,62)=10.75, p=0.002. In this same context, women who were motivated to affiliate with the experimenter following oxytocin administration showed this effect in greater magnitude t(57)=-2.04, p=0.047, but showed the reverse effect (i.e. increased perceived support in response to oxytocin) when social contact with the experimenter was available t(57)=2.78, p=0.007. Male participants did not evidence this pattern. These findings support the role of oxytocin in social support seeking in distressed women, and highlight the negative consequences of increasing oxytocin bioavailability in the absence of social support. Supportive relationships may be necessary to elicit the prosocial effects oxytocin. Copyright © 2016 Elsevier Ltd. All rights reserved.

Low Fasting Oxytocin Levels Are Associated With Psychopathology in Anorexia Nervosa in Partial Recovery.

PubMed

Afinogenova, Yuliya; Schmelkin, Cindy; Plessow, Franziska; Thomas, Jennifer J; Pulumo, Reitumetse; Micali, Nadia; Miller, Karen K; Eddy, Kamryn T; Lawson, Elizabeth A

2016-11-01

Anorexia nervosa (AN), a psychiatric disorder characterized by restriction of food intake despite severe weight loss, is associated with increased comorbid anxiety and depression. Secretion of oxytocin, an appetite-regulating neurohormone with anxiolytic and antidepressant properties, is abnormal in AN. The link between oxytocin levels and psychopathology in AN has not been well explored. We performed a cross-sectional study of 79 women aged 18-45 years (19 AN, 26 AN in partial recovery [ANPR], and 34 healthy controls [HC]) investigating the relationship between basal oxytocin levels and disordered eating psychopathology, anxiety, and depressive symptoms. AN diagnoses were based on DSM-5 criteria. Data acquisition took place between December 2008 and March 2014. Fasting serum oxytocin levels were obtained, and the following self-report measures were used to assess psychopathology: Eating Disorder Examination Questionnaire, State-Trait Anxiety Inventory, and Beck Depression Inventory-II. Fasting oxytocin levels were low in ANPR compared to HC (P = .0004). In ANPR but not AN, oxytocin was negatively associated with disordered eating psychopathology (r = -0.39, P = .0496) and anxiety symptoms (state anxiety: r = -0.53, P = .006; trait anxiety: r = -0.49, P = .01). Furthermore, ANPR with significant disordered eating psychopathology, anxiety symptoms, or depressive symptoms had lower oxytocin levels compared to those with minimal or no symptoms (P = .04, .02, and .007, respectively). We speculate that a dysregulation of oxytocin pathways may contribute to persistent psychopathology after partial weight recovery from anorexia nervosa. © Copyright 2016 Physicians Postgraduate Press, Inc.

Oxytocin and Serotonin Brain Mechanisms in the Nonhuman Primate.

PubMed

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

Effects of acute doses of prosocial drugs methamphetamine and alcohol on plasma oxytocin levels.

PubMed

Bershad, Anya K; Kirkpatrick, Matthew G; Seiden, Jacob A; de Wit, Harriet

2015-06-01

Many drugs, including alcohol and stimulants, demonstrably increase sociability and verbal interaction and are recreationally consumed in social settings. One drug, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), seems to produce its prosocial effects by increasing plasma oxytocin levels, and the oxytocin system has been implicated in responses to several other drugs of abuse. Here, we sought to investigate the effects of 2 other "social" drugs on plasma oxytocin levels--methamphetamine and alcohol. Based on their shared capacity to enhance sociability, we hypothesized that both methamphetamine and alcohol would increase plasma oxytocin levels. In study 1, 11 healthy adult volunteers attended 3 sessions during which they received methamphetamine (10 mg or 20 mg) or placebo under double-blind conditions. Subjective drug effects, cardiovascular effects, and plasma oxytocin levels were measured at regular intervals throughout the sessions. In study 2, 8 healthy adult volunteers attended a single session during which they received 1 beverage containing placebo, and then a beverage containing alcohol (0.8 g/kg). Subjective effects, breath alcohol levels, and plasma oxytocin levels were measured at regular intervals. Both methamphetamine and alcohol produced their expected physiological and subjective effects, but neither of these drugs increased plasma oxytocin levels. The neurobiological mechanisms mediating the prosocial effects of drugs such as alcohol and methamphetamine remain to be identified.

Effects of MDMA and Intranasal Oxytocin on Social and Emotional Processing

PubMed Central

Kirkpatrick, Matthew G; Lee, Royce; Wardle, Margaret C; Jacob, Suma; de Wit, Harriet

2014-01-01

MDMA (±3,4-methylenedioxymethamphetamine, ‘ecstasy') is used recreationally, reportedly because it increases feelings of empathy, sociability, and interpersonal closeness. One line of evidence suggests that MDMA produces these effects by releasing oxytocin, a peptide involved in social bonding. In the current study, we investigated the acute effects of MDMA and oxytocin on social and emotional processing in healthy human volunteers. MDMA users (N=65) participated in a 4-session, within-between-subjects study in which they received oral MDMA (0.75, 1.5 mg/kg), intranasal oxytocin (20 or 40 IU), or placebo under double-blind conditions. The primary outcomes included measures of emotion recognition and sociability (desire to be with others). Cardiovascular and subjective effects were also assessed. As expected, MDMA dose-dependently increased heart rate and blood pressure and feelings of euphoria (eg, ‘High' and ‘Like Drug'). On measures of social function, MDMA impaired recognition of angry and fearful facial expressions, and the larger dose (1.5 mg/kg) increased desire to be with others, compared with placebo. Oxytocin produced small but significant increases in feelings of sociability and enhanced recognition of sad facial expressions. Additionally, responses to oxytocin were related to responses to MDMA with subjects on two subjective measures of sociability. Thus, MDMA increased euphoria and feelings of sociability, perhaps by reducing sensitivity to subtle signs of negative emotions in others. The present findings provide only limited support for the idea that oxytocin produces the prosocial effects of MDMA. PMID:24448644

A matter of distance-The effect of oxytocin on social discounting is empathy-dependent.

PubMed

Strang, Sabrina; Gerhardt, Holger; Marsh, Nina; Oroz Artigas, Sergio; Hu, Yang; Hurlemann, René; Park, Soyoung Q

2017-04-01

Generosity is an important behavior enriching human society and can be observed across cultures. However, generosity has been shown to be modulated as a function of social distance, also referred to as social discounting. Oxytocin and empathy are other factors that have been shown to play an important role in generous behavior. However, how exactly oxytocin and empathy impact social discounting is yet unknown. Here, we administered oxytocin or placebo in a double-blind design, and measured social discounting behavior. Additionally, individual differences in empathy were assessed. Our results show that the effect of oxytocin on generous behavior is modulated by trait empathy; only for those subjects who received oxytocin there was a positive correlation between individual trait empathy and their generous behavior towards close others. Copyright © 2017 Elsevier Ltd. All rights reserved.

Oral misoprostol versus oxytocin in the management of the third stage of labour.

PubMed

Parsons, Steven M; Walley, Robert L; Crane, Joan M G; Matthews, Kay; Hutchens, Donna

2006-01-01

To compare the effects of oral misoprostol 800 mug with intramuscular oxytocin 10 IU in routine management of the third stage of labour. This randomized controlled trial was performed in a rural district hospital in Ghana, West Africa, and enrolled women in labour with anticipated vaginal delivery and no known medical contraindication to prostaglandin administration. Women were randomized to receive oral misoprostol 800 mug or intramuscular oxytocin 10 IU. Blood samples were taken to determine hemoglobin concentration before delivery and at 12 hours post partum. Treatment was administered at delivery of the anterior shoulder. The primary outcome was the change in hemoglobin concentration from before to after delivery. Secondary outcomes included other measures of blood loss and presumed medication side effects. In total, 450 women were enrolled in the study. Their baseline characteristics were similar. There was no significant difference between the groups in the change in hemoglobin concentration (misoprostol 1.07 g/dL and oxytocin 1.00 g/dL). The only significant secondary outcomes were shivering (80.7% with misoprostol vs. 3.6% with oxytocin) and pyrexia (11.4% with misoprostol, none with oxytocin). Routine use of oral misoprostol 800 microg appears to be as effective as 10 IU parenteral oxytocin in minimizing blood loss during the third stage of labour, as determined by change in hemoglobin concentration. Misoprostol appears to be a safe, inexpensive, and effective uterotonic for use in rural and remote areas, where intravenous oxytocin may be unavailable.

Working hard for oneself or others: Effects of oxytocin on reward motivation in social anxiety disorder.

PubMed

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.

Postprandial oxytocin secretion is associated with severity of anxiety and depressive symptoms in anorexia nervosa

PubMed Central

Lawson, Elizabeth A.; Holsen, Laura M.; Santin, McKale; DeSanti, Rebecca; Meenaghan, Erinne; Eddy, Kamryn T.; Herzog, David B.; Goldstein, Jill M.; Klibanski, Anne

2013-01-01

Objective 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 (AN), and decreased levels in weight-recovered women with anorexia nervosa (ANWR) compared to healthy controls (HC). A meal may represent a significant source of stress in patients with disordered eating. We therefore investigated the association between post-prandial oxytocin secretion and symptoms of anxiety and depression in anorexia nervosa. Method We performed a cross-sectional study of 35 women (13 AN, 9 ANWR and 13 HC). Serum oxytocin and cortisol and plasma leptin levels were measured fasting and 30, 60, and 120min 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). Results In women with anorexia nervosa, oxytocin AUC and post-prandial nadir and peak levels were positively associated with STAI scores. Oxytocin AUC and nadir levels were positively associated with BDI-II scores. After controlling for cortisol AUC, most relationships remained significant. After controlling for leptin AUC, all of the relationships remained significant. Oxytocin secretion explained up to 51% of the variance in STAI trait and 24% of BDI-II scores. Conclusions Abnormal post-prandial oxytocin secretion in women with anorexia nervosa is associated with increased symptoms of anxiety and depression. This may represent an adaptive response of oxytocin secretion to food-related symptoms of anxiety and depression. PMID:23759466

Effects of oxytocin on high intensity focused ultrasound (HIFU) ablation of adenomysis: a prospective study.

PubMed

Zhang, Xin; Zou, Min; Zhang, Cai; He, Jia; Mao, Shihua; Wu, Qingrong; He, Min; Wang, Jian; Zhang, Ruitao; Zhang, Lian

2014-09-01

To investigate the effects of oxytocin on high-intensity focused ultrasound (HIFU) ablation for the treatment of adenomyosis. Eighty-six patients with adenomyosis from three hospitals were randomly assigned to the oxytocin group or control group for HIFU treatment. During HIFU treatment, 80 units of oxytocin was added in 500ml of 0.9% normal saline running at the rate of 2ml/min (0.32U/min) in the oxytocin group, while 0.9% normal saline was used in the control group. Both patients and HIFU operators were blinded to oxytocin or saline application. Treatment results, adverse effects were compared. When using oxytocin, the non-perfused volume (NPV) ratio was 80.7±11.6%, the energy-efficiency factor (EEF) was 8.1±9.9J/mm(3), and the sonication time required to ablate 1cm(3) was 30.0±36.0s/cm(3). When not using oxytocin, the non-perfused volume ratio was 70.8±16.7%, the EEF was 15.8±19.6J/mm(3), and the sonication time required to ablate 1cm(3) was 58.2±72.7S/cm(3). Significant difference in the NPV ratio, EEF, and the sonication time required to ablate 1cm(3) between the two groups was observed. No oxytocin related adverse effects occurred. Oxytocin could significantly decrease the energy for ablating adenomyosis with HIFU, safely enhance the treatment efficiency. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Off-label intranasal oxytocin use in adults is associated with increased amygdala-cingulate resting-state connectivity.

PubMed

Kovács, B; Kéri, S

2015-06-01

Intranasally administered oxytocin gained popularity as a hormone facilitating trust, cooperation, and affiliation. However, the long-term consequences of oxytocin use are not known. Given that intensive media attention and advertisements of the "love hormone" might lead to a new form of misuse, we conducted an online survey and identified 41 individuals with oxytocin misuse. Misuse will be proposed throughout the manuscript instead of the more accurate "off-label use" for reasons of simplicity. We compared the social functions of oxytocin users with that of 41 matched control volunteers. We administered the "Reading the Mind in the Eyes Test" (RMET) and the National Institute of Health (NIH) Toolbox Adult Social Relationship Scales (NIH-ASRS) to delineate affective "theory of mind" and real-life social functions, respectively. Resting-state functional brain connectivity analyses were also carried out. Results revealed no significant differences between individuals with oxytocin misuse and control participants on the RMET and NIH-ASRS. However, individuals with oxytocin misuse showed an increased connectivity between the right amygdala and dorsal anterior cingulate cortex relative to the control group. Higher estimated cumulative doses of oxytocin were associated with enhanced amygdala-cingulate connectivity. These results show that individuals who have self-selected for and pursued oxytocin use have increased amygdala-cingulate resting connectivity, compared to individuals who have not used oxytocin, despite the lack of differences in RMET and NIH-ASRS scores. Further longitudinal studies are warranted to investigate the cause-effect relationship between oxytocin use and brain connectivity. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Serum Irisin and Oxytocin Levels as Predictors of Metabolic Parameters in Obese Children.

PubMed

Binay, Çiğdem; Paketçi, Cem; Güzel, Savaş; Samancı, Nedim

2017-06-01

Irisin and oxytocin can affect energy homeostasis and it has been suggested that they may play an important role in reducing obesity and diabetes. In this study, we aimed to determine the relationship between metabolic parameters (including irisin and oxytocin levels) and anthropometric parameters in obese children. Ninety obese children (mean age, 13.85±1.63 years) and 30 healthy controls (mean age, 14.32±1.58 years) were enrolled in this study. Anthropometric and laboratory parameters (glucose, insulin, lipid, oxytocin, and irisin levels) were analyzed. The serum irisin and oxytocin levels were measured by enzyme-linked immunosorbent assay. Bioelectrical impedance was used to determine body composition. Irisin level was higher in the patients than in the controls (p=0.018), and this higher irisin level was correlated with increased systolic blood pressure, body mass index, waist/hip ratio, fat percentage, fat mass, glucose level, insulin level, and homeostasis model assessment of insulin resistance. Serum oxytocin level was significantly decreased in obese children compared to the controls (p=0.049). Also, among the 60 obese patients, oxytocin level was significantly lower in patients with than in those without metabolic syndrome (8.65±2.69 vs. 10.87±5.93 ng/L, respectively), while irisin levels were comparable (p=0.049 and p=0.104, respectively). There were no statistically significant relationships between oxytocin or irisin levels and lipid levels (p>0.05). Obese children had significantly higher irisin levels than the healthy controls. Additionally, this study shows for the first time that oxytocin level is significantly lower in obese compared with non-obese children and also lower in obese children with metabolic syndrome compared to those without.

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

PubMed

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

Effects of oxytocin on background anxiety in rats with high or low baseline startle

PubMed Central

Ayers, Luke; Agostini, Andrew; Schulkin, Jay; Rosen, Jeffrey B.

2016-01-01

Rationale Oxytocin has antianxiety properties in humans and rodents. However, the antianxiety effects have been variable. Objectives To reduce variability and strengthen to the antianxiety effect of oxytocin in fear-potentiated startle, two experiments were performed. First, different amounts of light-shock pairings were given to determine the optimal levels of cue-specific fear conditioning and non-predictable startle (background anxiety). Second, the antianxiety effects of oxytocin were examined in rats with high and low pre-fear conditioning baseline startle to determine if oxytocin differentially affects high and low trait anxiety rats. Methods Baseline pre-fear conditioning startle responses were first measured. Rats then received 1, 5 or 10 light-shock pairings. Fear-potentiated startle was then tested with two trial types: light-cued startle and non-cued startle trials. In the second experiment, rats fear conditioned with 10 light-shock pairings were administered either saline or oxytocin before a fear-potentiated startle test. Rats were categorized as low or high startlers by their pre-fear conditioning startle amplitude. Results Ten shock-pairings produced the largest non-cued startle responses (background anxiety), without increasing cue-specific fear-potentiated startle compared to 1 and 5 light-shock pairings. Cue-specific fear-potentiated startle was unaffected by oxytocin. Oxytocin reduced background anxiety only in rats with low pre-fear startle responses. Conclusions Oxytocin has population selective antianxiety effects on non-cued unpredictable threat, but only in rats with low pre-fear baseline startle responses. The low startle responses are reminiscent of humans with low startle responses and high trait anxiety. PMID:27004789

A single dose of oxytocin nasal spray improves higher-order social cognition in schizophrenia.

PubMed

Guastella, Adam J; Ward, Philip B; Hickie, Ian B; Shahrestani, Sara; Hodge, Marie Antoinette Redoblado; Scott, Elizabeth M; Langdon, Robyn

2015-11-01

Schizophrenia is associated with significant impairments in both higher and lower order social cognitive performance and these impairments contribute to poor social functioning. People with schizophrenia report poor social functioning to be one of their greatest unmet treatment needs. Recent studies have suggested the potential of oxytocin as such a treatment, but mixed results render it uncertain what aspects of social cognition are improved by oxytocin and, subsequently, how oxytocin might best be applied as a therapeutic. The aim of this study was to determine whether a single dose of oxytocin improved higher-order and lower-order social cognition performance for patients with schizophrenia across a well-established battery of social cognition tests. Twenty-one male patients received both a single dose of oxytocin nasal spray (24IU) and a placebo, two weeks apart in a randomized within-subjects placebo controlled design. Following each administration, participants completed the social cognition tasks, as well as a test of general neurocognition. Results revealed that oxytocin particularly enhanced performance on higher order social cognition tasks, with no effects on general neurocognition. Results for individual tasks showed most improvement on tests measuring appreciation of indirect hints and recognition of social faux pas. These results suggest that oxytocin, if combined to enhance social cognition learning, may be beneficial when targeted at higher order social cognition domains. This study also suggests that these higher order tasks, which assess social cognitive processing in a social communication context, may provide useful markers of response to oxytocin in schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

Oxytocin course over pregnancy and postpartum period and the association with postpartum depressive symptoms.

PubMed

Jobst, Andrea; Krause, Daniela; Maiwald, Carina; Härtl, Kristin; Myint, Aye-Mu; Kästner, Ralph; Obermeier, Michael; Padberg, Frank; Brücklmeier, Benedikt; Weidinger, Elif; Kieper, Susann; Schwarz, Markus; Zill, Peter; Müller, Norbert

2016-08-01

During the postpartum period, women are at higher risk of developing a mental disorder such as postpartum depression (PPD), a disorder that associates with mother-infant bonding and child development. Oxytocin is considered to play a key role in mother-infant bonding and social interactions and altered oxytocin plasma concentrations were found to be associated with PPD. In the present study, we evaluated oxytocin plasma levels and depressive symptoms during pregnancy and the postpartum period in healthy women. We evaluated 100 women twice during pregnancy (weeks 35 and 38) and three times in the postpartum period (within 2 days and 7 weeks and 6 months after delivery) by measuring oxytocin plasma levels with enzyme-linked immunosorbent assay (ELISA) and assessing depressive symptoms with the Montgomery-Asberg Depression Rating Scale. Oxytocin plasma levels significantly increased from the 35th week of gestation to 6 months postpartum in all women. However, levels decreased from the 38th week of gestation to 2 days after delivery in participants with postpartum depressive symptoms, whereas they continuously increased in the group without postpartum depressive symptoms; the difference between the course of oxytocin levels in the two groups was significant (Δt2-t3: t = 2.14; p = 0.036*). Previous depressive episodes and breastfeeding problems predicted postpartum depressive symptoms. Our results indicate that alterations in the oxytocin system during pregnancy might be specific for women who develop postpartum depressive symptoms. Future studies should investigate whether oxytocin plasma levels might have predictive value in women at high risk for PPD.

Involvement of histaminergic and noradrenergic receptors in the oxytocin-induced food intake in neonatal meat-type chicks.

PubMed

Mirnaghizadeh, Seyed Vahid; Zendehdel, Morteza; Babapour, Vahab

2017-03-01

Oxytocin neurons have a physiological role in food intake and energy balance. Several studies have shown that central histaminergic and adrenergic systems synapse on oxytocin neurons but there is no information for their interaction on food intake regulation in birds. The purpose of this study was to examine the effects of intracerebroventricular (ICV) injection of α-fluoromethylhistidine (α-FMH, histidine decarboxylase inhibitor), chlorpheniramine (histamine H1 receptors antagonist), famotidine (histamine H2 receptors antagonist), thioperamide (histamine H3 receptors antagonist), prazosin (α1 receptor antagonist), yohimbine (α2 receptor antagonist), metoprolol (β1 adrenergic receptor antagonist), ICI 118,551 (β2 adrenergic receptor antagonist) and SR59230R (β3 adrenergic receptor antagonist) on oxytocin-induced hypophagia in 3-h food-deprived (FD 3 ) neonatal broiler chicken. In Experiment 1, 3 h-fasted chicks were given an ICV injection of saline, α-FMH (250 nmol), oxytocin (10 μg) and co-injection of α-FMH + oxytocin. Experiments 2-9 were similar to experiment 1 except birds were injected with chlorpheniramine (300 nmol), famotidine (82 nmol), thioperamide (300 nmol), prazosin (10 nmol), yohimbine (13 nmol), metoprolol (24 nmol), ICI 118,551(5 nmol) and SR59230R (20 nmol) instead of α-FMH, respectively. After injection cumulative food intake was measured until 120 min post injection. According to the results, ICV injection of oxytocin significantly decreased food intake in broiler chickens (P < 0.001). ICV injection of α-FMH significantly attenuated hypophagic effect of oxytocin (P < 0.001). Also, co-injection of chlorpheniramine plus oxytocin significantly decreased the effect of oxytocin on food intake (P < 0.001). Co-administration of thioperamide and oxytocin significantly amplified hypophagic effect of oxytocin in chickens (P < 0.001). In addition, ICI 118,551 attenuated hypophagic effect of oxytocin (P < 0.001); while

Ameliorating Impact of Prophylactic Intranasal Oxytocin on Signs of Fear in a Rat Model of Traumatic Stress

PubMed Central

Renicker, Micah D.; Cysewski, Nicholas; Palmer, Samuel; Nakonechnyy, Dmytro; Keef, Andrew; Thomas, Morgan; Magori, Krisztian; Daberkow, David P.

2018-01-01

Oxytocin treatment reduces signs of long-term emotional stress after exposure to trauma; however, little is known about the potential protective effects of oxytocin treatment on behavioral and physiological changes associated with extreme stress exposure. The objective of this study was to investigate oxytocin treatment as a prophylactic measure against rat signs of fear. Two separate experiments were conducted in which the time of intranasal oxytocin administration differed. Intranasal oxytocin (1.0 μg/kg) was administered 5 min after daily exposure to foot shock in Experiment #1 and 1 h before foot shock in Experiment #2. In Experiment #1, possible massage-evoked oxytocin release (5 min after foot shock) was also investigated. In both experiments, a contextual fear conditioning procedure was employed in which stress was induced via inescapable foot shock (3 days, 40 shocks/day, 8 mA/shock) in a fear conditioning chamber. Male Sprague-Dawley rats (n = 24) were divided into four groups (n = 6, per group) for each experiment. Experiment #1 groups: Control Exp#1 (intranasal saline and no foot shock); Stress Exp#1 (intranasal saline 5 min after foot shock); Massage+Stress Exp#1 (massage-like stroking and intranasal saline 5 min after foot shock); Oxytocin+Stress Exp#1 (intranasal oxytocin 5 min after foot shock). Experiment #2 groups: Control Exp#2 (intranasal saline and no foot shock); Stress Exp#2 (intranasal saline 1 h before foot shock); Oxytocin Exp#2 (intranasal oxytocin and no foot shock); Oxytocin+Stress Exp#2 (intranasal oxytocin 1 h before foot shock). One week after fear conditioning (and other treatments), rats were independently evaluated for behavioral signs of fear. Two weeks after conditioning, physiological signs of fear were also assessed (Experiment #1). Relative to controls, rats treated with intranasal oxytocin 5 min after daily foot shock sessions exhibited significantly less immobility upon re-exposure to the shock chamber and attenuated

Unsupportive social interactions and affective states: examining associations of two oxytocin-related polymorphisms.

PubMed

McInnis, Opal A; McQuaid, Robyn J; Matheson, Kimberly; Anisman, Hymie

2017-01-01

Two single-nucleotide polymorphisms (SNPs) on oxytocin-related genes, specifically the oxytocin receptor (OXTR) rs53576 and the CD38 rs3796863 variants, have been associated with alterations in prosocial behaviors. A cross-sectional study was conducted among undergraduate students (N = 476) to examine associations between the OXTR and CD38 polymorphisms and unsupportive social interactions and mood states. Results revealed no association between perceived levels of unsupportive social interactions and the OXTR polymorphism. However, A carriers of the CD38 polymorphism, a variant previously associated with elevated oxytocin, reported greater perceived peer unsupportive interactions compared to CC carriers. As expected, perceived unsupportive interactions from peers was associated with greater negative affect, which was moderated by the CD38 polymorphism. Specifically, this relation was stronger among CC carriers of the CD38 polymorphism (a variant thought to be linked to lower oxytocin). When examining whether the OXTR polymorphism moderated the relation between unsupportive social interactions from peers and negative affect there was a trend toward significance, however, this did not withstand multiple testing corrections. These findings are consistent with the perspective that a variant on an oxytocin polymorphism that may be tied to lower oxytocin is related to poor mood outcomes in association with negative social interactions. At the same time, having a genetic constitution presumed to be associated with higher oxytocin was related to increased perceptions of unsupportive social interactions. These seemingly paradoxical findings could be related to previous reports in which variants associated with prosocial behaviors were also tied to relatively more effective coping styles to deal with challenges.

Oxytocin Experiments Shed Light on Mechanisms Shaping Prosocial and Antisocial Behaviors in Non-human Mammals.

PubMed

Smith, Jennifer E; Petelle, Matthew B; Jerome, Emily L; Cristofari, Hélène; Blumstein, Daniel T

2017-09-01

Oxytocin has gained a reputation in popular culture as a simple "love drug" or "cuddle hormone", yet emerging biological evidence indicates that the effects of oxytocin are complex, mediating a suite of behavioral traits that range from ultrasocial to antisocial. Here we provide a comprehensive review to assess the salience of oxytocin in the lives of free-living social mammals. We reviewed the literature to understand the potential effects of oxytocin in promoting prosocial and antisocial behaviors in non-human mammals. Our review highlights a strong bias for studies of model organisms in highly-controlled settings, and emerging evidence for oxytocin's antisocial, context-specific and sex-specific effects. We discuss the results of the review in the context of insights gained from a pilot study aimed to investigate the potential for oxytocin to promote social cohesion in free-living yellow-bellied marmots (Marmota flaviventer). Our field experiment offers an example of the diverse issues that arise when conducting oxytocin manipulations in ecologically relevant contexts. Our synthesis highlights the challenges associated with acquiring adequate sample sizes for field-based, manipulative studies that require standardized measures of social behavior. Taken together, our findings lead us to join others in calling for revision of a simplistic view of oxytocin's role in regulating patterns of behavior. We draw from classical approaches used to study the mechanistic basis of behavior and offer a useful guide for disentangling these effects while appreciating the complex actions of oxytocin in shaping mammalian social behavior. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Severity of Withdrawal Symptoms, Plasma Oxytocin Levels, and Treatment Outcome in Heroin Users Undergoing Acute Withdrawal.

PubMed

Nikolaou, Kakia; Kapoukranidou, Dorothea; Ndungu, Samuel; Floros, Georgios; Kovatsi, Leda

2017-01-01

Pre-clinical studies show that, following chronic opioid exposure, oxytocin neurons exhibit over-excitation upon withdrawal, causing an increase in oxytocin brain and plasma levels. Relevant clinical data on humans are scarce. This study investigates the opioid withdrawal stress effect on oxytocin plasma levels in humans. We evaluated 57 male chronic heroin users in a residential detoxification program. We determined plasma oxytocin levels by ELISA and measured the stress effects of withdrawal using the COWS scale for opioid withdrawal, the VAS scale for craving, and the Hamilton scales for anxiety and depression on the second day of admission. Out of the 57 patients enrolled in the study, 27 completed the 21-day program, while the remaining 30 dropped out prior to completion. Plasma oxytocin levels were significantly higher in those individuals who dropped out than in those who completed the program. Participants who dropped out at some stage scored higher in the COWS, VAS-Craving, and Hamilton-anxiety scales, indicating a higher stress and explaining the higher oxytocin levels. In addition, plasma oxytocin levels correlated positively with the scores achieved in the COWS and Hamilton-anxiety scales. Higher withdrawal stress levels are associated with higher plasma oxytocin levels and early treatment discharge.

Oxytocin does not make a face appear more trustworthy but improves the accuracy of trustworthiness judgments.

PubMed

Lambert, Bruno; Declerck, Carolyn H; Boone, Christophe

2014-02-01

Previous research on the relation between oxytocin and trustworthiness evaluations has yielded inconsistent results. The current study reports an experiment using artificial faces which allows manipulating the dimension of trustworthiness without changing factors like emotions or face symmetry. We investigate whether (1) oxytocin increases the average trustworthiness evaluation of faces (level effect), and/or whether (2) oxytocin improves the discriminatory ability of trustworthiness perception so that people become more accurate in distinguishing faces that vary along a gradient of trustworthiness. In a double blind oxytocin/placebo experiment (N=106) participants conducted two judgement tasks. First they evaluated the trustworthiness of a series of pictures of artificially generated faces, neutral in the trustworthiness dimension. Next they compared neutral faces with artificially generated faces that were manipulated to vary in trustworthiness. The results indicate that oxytocin (relative to a placebo) does not affect the evaluation of trustworthiness in the first task. However, in the second task, misclassification of untrustworthy faces as trustworthy occurred significantly less in the oxytocin group. Furthermore, oxytocin improved the discriminatory ability of untrustworthy, but not trustworthy faces. We conclude that oxytocin does not increase trustworthiness judgments on average, but that it helps people to more accurately recognize an untrustworthy face. Copyright © 2013 Elsevier Ltd. All rights reserved.

Recognition of oxytocin by capillary electrochromatography with monolithic tetrapeptide-imprinted polymer used as the stationary phase.

PubMed

Zheng, Chao; Liu, Zhaosheng; Gao, Ruyu; Zhang, Lihua; Zhang, Yukui

2007-07-01

Using YPLG (Tyr-Pro-Leu-Gly), a tetrapeptide, as the template, an imprinted monolithic column was prepared and applied to the selective recognition of oxytocin based on the epitope approach and capillary electrochromatography (CEC). By optimizing the polymerization solution in terms of functional monomer, cross-linking reagent, porogen, and imprinted template via CEC evaluations of synthesized columns, an imprinted monolith with good recognition capacity (the imprinting factors for YPLG and oxytocin were 4.499 and 4.013, respectively) and high column efficiency (theoretical plates for YPLG and oxytocin were 22,995 plates/m and 16,952 plates/m, respectively) was achieved. In addition, the effects of various experimental parameters on the recognition of oxytocin, including the organic modifier content, the buffer concentration, and the pH value, were studied systematically. Furthermore, a mixture of oxytocin and other proteins was analyzed using this monolithic CEC column, and oxytocin was eluted much more slowly than other large biomolecules, which demonstrated the high selective recognition ability of such an imprinted monolith for oxytocin with PLG (Pro-Leu-Gly) as the epitope. Figure Separation of a mixture of oxytocin, BSA, bovine hemoglobin, ovalbumin, and lysozyme on the open column, the blank monolithic column, and the monolithic YPLG-imprinted column.

Role of Prophylactic Oxytocin in the Third Stage of Labor: Physiologic Versus Pharmacologically Influenced Labor and Birth.

PubMed

Erickson, Elise N; Lee, Christopher S; Emeis, Cathy L

2017-07-01

Maternity care providers administer oxytocin prophylactically to prevent postpartum hemorrhage (PPH). Prophylactic oxytocin is generally considered effective and safe and is promoted by national organizations for standardized use. In this article, the evidence supporting prophylactic oxytocin administration for women undergoing spontaneous labor and birth compared with women whose labors included administration of exogenous oxytocin for induction or augmentation is explored. Using data from randomized controlled trials included in 2 recent Cochrane meta-analyses papers, only studies with women in spontaneous labor were selected for inclusion (N = 4 studies). Outcomes of immediate postpartum bleeding volumes (≥ 500 mL or 1000 mL), risk for blood transfusion, and risk for administration of more uterotonic medication were pooled from these 4 studies. Focused random effects meta-analytics were used. Compared to women without prophylactic oxytocin, women who received prophylactic oxytocin had a lower risk of having a 500 mL or higher blood loss. However, prophylactic oxytocin did not lower risk of PPH (≥ 1000 mL), blood transfusion, or need for additional uterotonic treatment. Prophylactic oxytocin may not confer the same benefits to women undergoing spontaneous labor and birth compared to women laboring with oxytocin infusion. Reasons for this difference are explored from a pharmacologic perspective. In addition, the value of prophylactic oxytocin given recent changes in the definition of PPH from greater than or equal to 500 mL to 1000 mL or more after birth is discussed. Finally, gaps in research on adverse effects of prophylactic oxytocin are presented. More research is needed on reducing risk of PPH for women in spontaneous labor. © 2017 by the American College of Nurse-Midwives.

Intranasal oxytocin in the treatment of autism spectrum disorders: a review of literature and early safety and efficacy data in youth.

PubMed

Anagnostou, Evdokia; Soorya, Latha; Brian, Jessica; Dupuis, Annie; Mankad, Deepali; Smile, Sharon; Jacob, Suma

2014-09-11

There is a paucity of treatments targeting core symptom domains in Autism Spectrum Disorder (ASD). Several animal models and research in typically developing volunteers suggests that manipulation of the oxytocin system may have therapeutic potential for the treatment of social deficits. We review the literature for oxytocin and ASD and report on early dosing, safety and efficacy data of multi-dose oxytocin on aspects of social cognition/function, as well as repetitive behaviors and co-occurring anxiety within ASD. Fifteen children and adolescents with verbal IQs≥70 were diagnosed with ASD using the ADOS and the ADI-R. They participated in a modified maximum tolerated dose study of intranasal oxytocin (Syntocinon). Data were modeled using repeated measures regression analysis controlling for week, dose, age, and sex. Among 4 doses tested, the highest dose evaluated, 0.4 IU/kg/dose, was found to be well tolerated. No serious or severe adverse events were reported and adverse events reported/observed were mild to moderate. Over 12 weeks of treatment, several measures of social cognition/function, repetitive behaviors and anxiety showed sensitivity to change with some measures suggesting maintenance of effect 3 months past discontinuation of intranasal oxytocin. This pilot study suggests that daily administration of intranasal oxytocin at 0.4 IU/kg/dose in children and adolescents with ASD is safe and has therapeutic potential. Larger studies are warranted. This article is part of a Special Issue entitled Oxytocin and Social Behav. Copyright © 2014 Elsevier B.V. All rights reserved.

Augmenting Prolonged Exposure therapy for PTSD with intranasal oxytocin: A randomized, placebo-controlled pilot trial.

PubMed

Flanagan, Julianne C; Sippel, Lauren M; Wahlquist, Amy; Moran-Santa Maria, Megan M; Back, Sudie E

2018-03-01

Posttraumatic stress disorder (PTSD) is a chronic, debilitating condition for which Prolonged Exposure (PE) therapy is highly efficacious. However, for some individuals, premature dropout and residual PTSD symptoms remain obstacles. The neuropeptide oxytocin is a promising candidate to enhance PE due to its ability to enhance 1) prosocial cognition and behavior, which are theorized to promote positive working alliance, and 2) extinction learning, which is the central mechanism of action underlying successful PE treatment. Despite a robust theoretical rationale, no studies to date have combined evidence-based psychotherapy for PTSD with oxytocin. This randomized, placebo-controlled, double-blind pilot trial examined the feasibility, safety, and preliminary efficacy of augmenting PE with oxytocin. Participants were 17 individuals with diverse index traumas. Participants self-administered intranasal oxytocin (40 IU) or matching placebo 45 min prior to each weekly PE therapy session. One adverse event occurred in the placebo group and three individuals dropped out (17.6%; 2 oxytocin group and 1 placebo group). The oxytocin group demonstrated lower PTSD and depression symptoms during PE, and had higher working alliance scores, although these differences did not reach statistical significance. Although preliminary, the findings support the feasibility of oxytocin combined with PE. Adequately powered studies are necessary to determine whether oxytocin enhances PE treatment outcomes and to examine potential mechanisms, such as accelerating extinction learning, enhancing early response, and preventing premature dropout. NCT03238924. Copyright © 2017. Published by Elsevier Ltd.

Effects of intranasal oxytocin on amygdala reactivity to emotional faces in recently trauma-exposed individuals.

PubMed

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

2016-02-01

There is a need for effective, early post-trauma preventive interventions for post-traumatic stress disorder (PTSD). Attenuating amygdala hyperreactivity early post-trauma, a likely PTSD vulnerability factor, may decrease PTSD risk. Since oxytocin modulates amygdala reactivity to emotional stimuli, oxytocin administration early post-trauma may be a promising candidate for PTSD prevention. In a randomized double-blind placebo-controlled fMRI study, we investigated effects of a single intranasal oxytocin administration (40 IU) on amygdala reactivity to happy, neutral and fearful faces in 41 recently trauma-exposed men and women showing moderate to high distress after initial post-trauma screening. We explored treatment interactions with sex. Participants were scanned within 11 days post-trauma. Compared with placebo, oxytocin significantly increased right amygdala reactivity to fearful faces. There was a significant treatment by sex interaction on amygdala reactivity to neutral faces, with women showing increased left amygdala reactivity after oxytocin. These findings indicate that a single oxytocin administration may enhance fearful faces processing in recently trauma-exposed individuals and neutral faces processing in recently trauma-exposed women. These observations may be explained by oxytocin-induced increased salience processing. Clinical implications of these findings for PTSD prevention should be further investigated. Netherlands Trial Registry; Boosting Oxytocin after trauma: Neurobiology and the Development of Stress-related psychopathology (BONDS); NTR3190; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC = 3190. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

The Relationship of the Administration of Intrapartum Synthetic Oxytocin and Breastfeeding Initiation and Duration Rates.

PubMed

Fernández-Cañadas Morillo, Aurora; Marín Gabriel, Miguel A; Olza Fernández, Ibone; Martínez Rodríguez, Begoña; Durán Duque, Modesto; Malalana Martínez, Ana M; Gonzalez Armengod, Carmen; Pérez Riveiro, Pilar; García Murillo, Lourdes

2017-03-01

The consequences that intrapartum administration of hormones can have on breastfeeding are unclear. The aim of the study is to determine if synthetic intrapartum oxytocin, used routinely for induction/stimulation, has a relationship to initiation/duration of breastfeeding. We conducted a cohort study that was carried out in a tertiary university hospital distinguished by WHO-UNICEF as a BFHI (Baby-Friendly Hospital Initiative). A group of 53 mother and newborn dyads who had been exposed to intrapartum synthetic oxytocin were compared with 45 nonexposed dyads. A breastfeeding questionnaire was administered by a midwife blind to patient group through phone calls 3 and 6 months after delivery. No statistically significant differences were observed between the two groups in the rates of mothers exclusively breastfeeding (EBF) or nonexclusively breastfeeding. The percentage of those who were EBF when discharged was 97.3% in the oxytocin-nonexposed group and 87.1% in the oxytocin-exposed group (p = 0.14). At 3 months, the group rates of exclusive breastfeeding were 72.5% in the nonoxytocin-exposed group versus 65.9% in the oxytocin-exposed group (p = 0.71). At 6 months, rates of breastfeeding were 31.4% versus 27.9% (p = 0.53) in the oxytocin-nonexposed and oxytocin-exposed groups, respectively. In this study, no statistically significant effect of intrapartum synthetic oxytocin administration was observed pertaining to the initiation or duration of breastfeeding.

Genetic variation in the oxytocin receptor (OXTR) gene is associated with Asperger Syndrome.

PubMed

Di Napoli, Agnese; Warrier, Varun; Baron-Cohen, Simon; Chakrabarti, Bhismadev

2014-01-01

Autism Spectrum Conditions (ASC) are a group of neurodevelopmental conditions characterized by impairments in communication and social interaction, alongside unusually repetitive behaviors and narrow interests. ASC are highly heritable and have complex patterns of inheritance where multiple genes are involved, alongside environmental and epigenetic factors. Asperger Syndrome (AS) is a subgroup of these conditions, where there is no history of language or cognitive delay. Animal models suggest a role for oxytocin (OXT) and oxytocin receptor (OXTR) genes in social-emotional behaviors, and several studies indicate that the oxytocin/oxytocin receptor system is altered in individuals with ASC. Previous studies have reported associations between genetic variations in the OXTR gene and ASC. The present study tested for an association between nine single nucleotide polymorphisms (SNPs) in the OXTR gene and AS in 530 individuals of Caucasian origin, using SNP association test and haplotype analysis. There was a significant association between rs2268493 in OXTR and AS. Multiple haplotypes that include this SNP (rs2268493-rs2254298, rs2268490-rs2268493-rs2254298, rs2268493-rs2254298-rs53576, rs237885-rs2268490-rs2268493-rs2254298, rs2268490-rs2268493-rs2254298-rs53576) were also associated with AS. rs2268493 has been previously associated with ASC and putatively alters several transcription factor-binding sites and regulates chromatin states, either directly or through other variants in linkage disequilibrium (LD). This study reports a significant association of the sequence variant rs2268493 in the OXTR gene and associated haplotypes with AS.

The Williams syndrome prosociality gene GTF2I mediates oxytocin reactivity and social anxiety in a healthy population.

PubMed

Procyshyn, Tanya L; Spence, Jason; Read, Silven; Watson, Neil V; Crespi, Bernard J

2017-04-01

The neurohormone oxytocin plays a central role in human social behaviour and cognition, and oxytocin dysregulation may contribute to psychiatric disorders. However, genetic factors influencing individual variation in the oxytocinergic system remain poorly understood. We genotyped 169 healthy adults for a functional polymorphism in GTF2I ( general transcription factor II-I ), a gene associated with high prosociality and reduced social anxiety in Williams syndrome, a condition reported to involve high oxytocin levels and reactivity. Participants' salivary oxytocin levels were measured before and after watching a validated empathy-inducing video. Oxytocin reactivity, defined as pre- to post-video percentage change in salivary oxytocin, varied substantially and significantly between individuals with different GTF2I genotypes, with, additionally, a trend towards an interaction between genotype and sex. Individuals with more oxytocin-reactive genotypes also reported significantly lower social anxiety. These findings suggest a model whereby GTF2I has a continuum of effects on human sociality, from the extreme social phenotypes and oxytocin dysregulation associated with gene deletion in Williams syndrome, to individual differences in oxytocin reactivity and sociality associated with common polymorphisms in healthy populations. © 2017 The Author(s).

Chemical identification of the mammalian oxytocin in a holocephalian fish, the ratfish (Hydrolagus colliei).

PubMed

Michel, G; Chauvet, J; Chauvet, M T; Clarke, C; Bern, H; Acher, R

1993-11-01

The neurohypophysial hormones of the ratfish (Hydrolagus colliei), a species belonging to the subclass Holocephali of cartilaginous fishes, have been investigated. An oxytocin-like hormone has been isolated from acetone-desiccated pituitary glands by using successively molecular sieving and high-pressure liquid chromatography. The peptide has been identified as oxytocin by coelution with synthetic oxytocin in HPLC, amino acid sequencing, mass spectrometry, and C-terminal sequencing through carboxypeptidase Y. Vasotocin may be present in a very small amount. Cartilaginous fishes appear to display a great diversity in their oxytocin-like hormones since five different peptides have been identified in rays and sharks that belong to the second subclass Selachii.

Interactions between dopamine and oxytocin in the control of sexual behaviour.

PubMed

Baskerville, Tracey A; Douglas, Alison J

2008-01-01

Dopamine and oxytocin are two key neuromodulators involved in reproductive behaviours, such as mating and maternal care. Much evidence underlies their separate roles in such behaviours, but particularly in sexual behaviour. It is generally believed that central dopaminergic and oxytocinergic systems work together to regulate the expression of penile erection, but relatively little is known regarding how they interact. Thus, this review aims to discuss neuroanatomical proof, neuromodulator secretory profiles in the hypothalamus and behavioural pharmacological evidence which support a dopamine-oxytocin link in three hypothalamic nuclei that have been implicated in sexual behaviour, namely the medial preoptic nucleus, supraoptic nucleus and paraventricular nucleus (PVN). We also aim to provide an overview of potential dopamine-mediated transduction pathways that occur within these nuclei and are correlated with the exhibition of penile erection. The PVN provides the most convincing evidence for a dopamine-oxytocin link and it is becoming increasingly apparent that parvocellular oxytocinergic neurons in the PVN, in part, mediate the effects of dopamine to elicit penile erection. However, while we show that oxytocin neurons express dopamine receptors, other evidence on whether dopaminergic activation of PVN oxytocin cells involves a direct and/or indirect mechanism is inconclusive and further evidence is required to establish whether the two systems interact synergistically or sequentially in the regulation of penile erection.

Endogenous testosterone and exogenous oxytocin influence the response to baby schema in the female brain.

PubMed

Holtfrerich, Sarah K C; Pfister, Roland; El Gammal, Alexander T; Bellon, Eugen; Diekhof, Esther K

2018-05-16

Nurturing behavior may be critically influenced by the interplay of different hormones. The neuropeptide oxytocin is known to promote maternal behavior and its reduction has been associated with postpartum depression risk and child neglect. Contrariwise, the observed decrease in testosterone level during early parenthood may benefit caretaking behavior, whereas increased testosterone may reduce attention to infants. Here we used functional magnetic resonance imaging to investigate the interactive influence of testosterone and oxytocin on selective attention to and neural processing of the baby schema (BS). 57 nulliparous women performed a target detection task with human faces with varying degree of BS following double-blinded placebo-controlled oxytocin administration in a between-subjects design. Our results support the idea that oxytocin enhances attention to the BS. Oxytocin had a positive effect on activation of the inferior frontal junction during identification of infant targets with a high degree of BS that were presented among adult distractors. Further, activation of the putamen was positively correlated with selective attention to the BS, but only in women with high endogenous testosterone who received oxytocin. These findings provide initial evidence for the neural mechanism by which oxytocin may counteract the negative effects of testosterone in the modulation of nurturing behavior.

Postprandial oxytocin secretion is associated with severity of anxiety and depressive symptoms in anorexia nervosa.

PubMed

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

Oxytocin Promotes Facial Emotion Recognition and Amygdala Reactivity in Adults with Asperger Syndrome

PubMed Central

Domes, Gregor; Kumbier, Ekkehardt; Heinrichs, Markus; Herpertz, Sabine C

2014-01-01

The neuropeptide oxytocin has recently been shown to enhance eye gaze and emotion recognition in healthy men. Here, we report a randomized double-blind, placebo-controlled trial that examined the neural and behavioral effects of a single dose of intranasal oxytocin on emotion recognition in individuals with Asperger syndrome (AS), a clinical condition characterized by impaired eye gaze and facial emotion recognition. Using functional magnetic resonance imaging, we examined whether oxytocin would enhance emotion recognition from facial sections of the eye vs the mouth region and modulate regional activity in brain areas associated with face perception in both adults with AS, and a neurotypical control group. Intranasal administration of the neuropeptide oxytocin improved performance in a facial emotion recognition task in individuals with AS. This was linked to increased left amygdala reactivity in response to facial stimuli and increased activity in the neural network involved in social cognition. Our data suggest that the amygdala, together with functionally associated cortical areas mediate the positive effect of oxytocin on social cognitive functioning in AS. PMID:24067301

Oxytocin promotes facial emotion recognition and amygdala reactivity in adults with asperger syndrome.

PubMed

Domes, Gregor; Kumbier, Ekkehardt; Heinrichs, Markus; Herpertz, Sabine C

2014-02-01

The neuropeptide oxytocin has recently been shown to enhance eye gaze and emotion recognition in healthy men. Here, we report a randomized double-blind, placebo-controlled trial that examined the neural and behavioral effects of a single dose of intranasal oxytocin on emotion recognition in individuals with Asperger syndrome (AS), a clinical condition characterized by impaired eye gaze and facial emotion recognition. Using functional magnetic resonance imaging, we examined whether oxytocin would enhance emotion recognition from facial sections of the eye vs the mouth region and modulate regional activity in brain areas associated with face perception in both adults with AS, and a neurotypical control group. Intranasal administration of the neuropeptide oxytocin improved performance in a facial emotion recognition task in individuals with AS. This was linked to increased left amygdala reactivity in response to facial stimuli and increased activity in the neural network involved in social cognition. Our data suggest that the amygdala, together with functionally associated cortical areas mediate the positive effect of oxytocin on social cognitive functioning in AS.

Polymorphism and genetic mapping of the human oxytocin receptor gene on chromosome 3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Michelini, S.; Urbanek, M.; Goldman, D.

1995-06-19

Centrally administered oxytocin has been reported to facilitate affiliative and social behaviors, in functional harmony with its well-known peripheral effects on uterine contraction and milk ejection. The biological effects of oxytocin could be perturbed by mutations occurring in the sequence of the oxytocin receptor gene, and it would be of interest to establish the position of this gene on the human linkage map. Therefore we identified a polymorphism at the human oxytocin receptor gene. A portion of the 3{prime} untranslated region containing a 30 bp CA repeat was amplified by polymerase chain reaction (PCR), revealing a polymorphism with two allelesmore » occurring with frequencies of 0.77 and 0.23 in a sample of Caucasian CEPH parents (n = 70). The CA repeat polymorphism we detected was used to map the human oxytocin receptor to chromosome 3p25-3p26, in a region which contains several important genes, including loci for Von Hippel-Lindau disease (VHL) and renal cell carcinoma. 53 refs., 2 figs., 1 tab.« less

Exploring dissociation and oxytocin as pathways between trauma exposure and trauma-related hyperemesis gravidarum: a test-of-concept pilot

PubMed Central

SENG, JULIA; MILLER, JANIS; SPERLICH, MICKEY; VAN DE VEN, COSMAS J. M.; BROWN, STEPHANIE; CARTER, C. SUE; LIBERZON, ISRAEL

2012-01-01

Posttraumatic stress disorder (PTSD) is associated with gastrointestinal and genitourinary comorbidities. These map onto the somatization disorder symptoms in the Diagnostic and Statistical Manual of Mental Disorders (APA, 1994) and the dissociative [conversion] disorders symptoms in the International Classification of Diseases taxonomy (WHO, 2007). Hyperemesis gravidarum (HG) is one of these symptoms and a gastrointestinal comorbidity of PTSD occurring in pregnancy. It is an idiopathic condition defined as severe vomiting with dehydration, metabolic imbalance, wasting, and hospital care-seeking. HG is more severe than the normative phenomenon of nausea and vomiting of pregnancy (NV). This test-of-concept pilot (N=25) explored the hypothesis that there is a trauma-related subtype of HG characterized by (1) high levels of dissociative symptoms and (2) altered plasma concentrations of oxytocin. This hypothesis is informed by a theory of posttraumatic oxytocin dysregulation positing altered oxytocin function as a mechanism of gut smooth muscle peristalsis dysfunction. A four-group analysis compared controls with nausea and vomiting of pregnancy (NV only) and cases with HG only, NV and PTSD, or HG and PTSD. Oxytocin was correlated with nausea and vomiting symptom severity score (r = .464, p = .019) and with the dissociation symptom score (r = .570, p = .003). Women in the group with both PTSD and HG (the “trauma-related HG subtype”) had the highest levels of dissociation and the highest levels of oxytocin. A linear regression model indicated that the independent association of the trauma-related HG subtype with oxytocin level was mediated by high levels of dissociative symptoms. PMID:23282046

Role of oxytocin signaling in the regulation of body weight.

PubMed

Blevins, James E; Ho, Jacqueline M

2013-12-01

Obesity and its associated metabolic disorders are growing health concerns in the US and worldwide. In the US alone, more than two-thirds of the adult population is classified as either overweight or obese [1], highlighting the need to develop new, effective treatments for these conditions. Whereas the hormone oxytocin is well known for its peripheral effects on uterine contraction during parturition and milk ejection during lactation, release of oxytocin from somatodendrites and axonal terminals within the central nervous system (CNS) is implicated in both the formation of prosocial behaviors and in the control of energy balance. Recent findings demonstrate that chronic administration of oxytocin reduces food intake and body weight in diet-induced obese (DIO) and genetically obese rodents with impaired or defective leptin signaling. Importantly, chronic systemic administration of oxytocin out to 6 weeks recapitulates the effects of central administration on body weight loss in DIO rodents at doses that do not result in the development of tolerance. Furthermore, these effects are coupled with induction of Fos (a marker of neuronal activation) in hindbrain areas (e.g. dorsal vagal complex (DVC)) linked to the control of meal size and forebrain areas (e.g. hypothalamus, amygdala) linked to the regulation of food intake and body weight. This review assesses the potential central and peripheral targets by which oxytocin may inhibit body weight gain, its regulation by anorexigenic and orexigenic signals, and its potential use as a therapy that can circumvent leptin resistance and reverse the behavioral and metabolic abnormalities associated with DIO and genetically obese models.

Role of oxytocin signaling in the regulation of body weight

PubMed Central

Blevins, James E.; Ho, Jacqueline M.

2014-01-01

Obesity and its associated metabolic disorders are growing health concerns in the US and worldwide. In the US alone, more than two-thirds of the adult population is classified as either overweight or obese [1], highlighting the need to develop new, effective treatments for these conditions. Whereas the hormone oxytocin is well known for its peripheral effects on uterine contraction during parturition and milk ejection during lactation, release of oxytocin from somatodendrites and axonal terminals within the central nervous system (CNS) is implicated in both the formation of prosocial behaviors and in the control of energy balance. Recent findings demonstrate that chronic administration of oxytocin reduces food intake and body weight in diet-induced obese (DIO) and genetically obese rodents with impaired or defective leptin signaling. Importantly, chronic systemic administration of oxytocin out to 6 weeks recapitulates the effects of central administration on body weight loss in DIO rodents at doses that do not result in the development of tolerance. Furthermore, these effects are coupled with induction of Fos (a marker of neuronal activation) in hindbrain areas (e.g. dorsal vagal complex (DVC)) linked to the control of meal size and forebrain areas (e.g. hypothalamus, amygdala) linked to the regulation of food intake and body weight. This review assesses the potential central and peripheral targets by which oxytocin may inhibit body weight gain, its regulation by anorexigenic and orexigenic signals, and its potential use as a therapy that can circumvent leptin resistance and reverse the behavioral and metabolic abnormalities associated with DIO and genetically obese models. PMID:24065622

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

PubMed Central

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

Low oxytocin and melatonin levels and their possible role in the diagnosis and prognosis in Iraqi autistic children.

PubMed

Abdulamir, Haidar A; Abdul-Rasheed, Omar F; Abdulghani, Emad A

2016-01-01

  To test the possible association between oxytocin and melatonin levels with the severity of social and cognitive dysfunctions, and to study the correlation between these parameters in children with autism. A case-control study was carried out in the Department of Chemistry and Biochemistry, College of Medicine, Al-Nahrain University, Baghdad, Iraq. The study was performed on 60 male autistic patients recruited from the Pediatric Department of Al-Sader General Hospital, Baghdad, Iraq between November 2014 and April 2015. The levels of oxytocin and melatonin were measured in the serum of these autistic male patients, and categorized as mild, moderate, and severe (20 patients each), and was compared with 26 age- and gender-matched control subjects. The data indicated that the levels of oxytocin (44.72 ± 36.1 μIU/mL) and melatonin in patients (23.08 ± 10.41 pg/mL) were significantly lower (p less than 0.05) than that of age-matched (102.1 ± 34.31 μIU/mL) and gender-matched controls (53.05 ± 38.38 pg/mL). These parameters were remarkably associated with the severity of the disease that was indicated by the significant decrease in the levels of oxytocin (47 ± 25.47 μIU/mL) and melatonin in moderate (20 ± 6.14 pg/mL), and patients with severe oxytocin (27.92 ± 10.23 μIU/mL) and patients with severe melatonin (21.69 ± 7.02 pg/mL) when compared with mild autistic patients with oxytocin (59.22 ± 27.32 μIU/mL) and melatonin (27.55 ± 14.71 pg/mL). These 2 parameters showed a significant positive correlation with each other in moderate (r=0.513; p=0.021), and severe patients (r=0.598; p=0.005).  Receiver operating characteristic analysis revealed that oxytocin can be considered as a good diagnostic marker in severe autistic patients while melatonin can be considered as a good diagnostic marker in all autistic subgroups. This study proves the possibility of using oxytocin and melatonin in the diagnosis, and as markers of autism severity.

Low oxytocin and melatonin levels and their possible role in the diagnosis and prognosis in Iraqi autistic children

PubMed Central

Abdulamir, Haidar A.; Abdul-Rasheed, Omar F.; Abdulghani, Emad A.

2016-01-01

Objectives: To test the possible association between oxytocin and melatonin levels with the severity of social and cognitive dysfunctions, and to study the correlation between these parameters in children with autism. Methods: A case-control study was carried out in the Department of Chemistry and Biochemistry, College of Medicine, Al-Nahrain University, Baghdad, Iraq. The study was performed on 60 male autistic patients recruited from the Pediatric Department of Al-Sader General Hospital, Baghdad, Iraq between November 2014 and April 2015. The levels of oxytocin and melatonin were measured in the serum of these autistic male patients, and categorized as mild, moderate, and severe (20 patients each), and was compared with 26 age- and gender-matched control subjects. Results: The data indicated that the levels of oxytocin (44.72 ± 36.1 µIU/mL) and melatonin in patients (23.08 ± 10.41 pg/mL) were significantly lower (p<0.05) than that of age-matched (102.1 ± 34.31 µIU/mL) and gender-matched controls (53.05 ± 38.38 pg/mL). These parameters were remarkably associated with the severity of the disease that was indicated by the significant decrease in the levels of oxytocin (47 ± 25.47 µIU/mL) and melatonin in moderate (20 ± 6.14 pg/mL), and patients with severe oxytocin (27.92 ± 10.23 µIU/mL) and patients with severe melatonin (21.69 ± 7.02 pg/mL) when compared with mild autistic patients with oxytocin (59.22 ± 27.32 µIU/mL) and melatonin (27.55 ± 14.71 pg/mL). These 2 parameters showed a significant positive correlation with each other in moderate (r=0.513; p=0.021), and severe patients (r=0.598; p=0.005). Conclusion: Receiver operating characteristic analysis revealed that oxytocin can be considered as a good diagnostic marker in severe autistic patients while melatonin can be considered as a good diagnostic marker in all autistic subgroups. This study proves the possibility of using oxytocin and melatonin in the diagnosis, and as markers of autism

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

PubMed

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.

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

PubMed

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.

"The role of oxytocin in psychiatric disorders: A review of biological and therapeutic research findings"

PubMed Central

Cochran, David; Fallon, Daniel; Hill, Michael; Frazier, Jean A.

2014-01-01

Oxytocin is a peptide hormone integral in parturition, milk let-down, and maternal behaviors that has been demonstrated in animal studies to be important in the formation of pair bonds and in social behaviors. This hormone is increasingly recognized as an important regulator of human social behaviors, including social decision making, evaluating and responding to social stimuli, mediating social interactions, and forming social memories. In addition, oxytocin is intricately involved in a broad array of neuropsychiatric functions, and may be a common factor important in multiple psychiatric disorders such as autism, schizophrenia, mood and anxiety disorders. This review article examines the extant literature on the evidence for oxytocin dysfunction in a variety of psychiatric disorders and highlights the need for further research to understand the complex role of the oxytocin system in psychiatric disease to pave the way for developing new therapeutic modalities. Articles were selected that involved human participants with various psychiatric disorders, either comparing oxytocin biology to healthy controls or examining the effects of exogenous oxytocin administration. PMID:24651556

Oxytocin decreases handgrip force in reaction to infant crying in females without harsh parenting experiences.

PubMed

Bakermans-Kranenburg, Marian J; van Ijzendoorn, Marinus H; Riem, Madelon M E; Tops, Mattie; Alink, Lenneke R A

2012-11-01

Infant crying can elicit sensitive caregiving as well as hostility and harsh parenting responses. In the current study (N = 42 females) with a double-blind experimental design, we tested the effect of intranasal oxytocin administration on the use of excessive force using a hand-grip dynamometer during listening to infant cry sounds. Participants' experiences with harsh parental discipline during childhood were found to moderate the effect of oxytocin administration on the use of excessive force. Participants' whose parents did not discipline them harshly used less excessive force in the oxytocin condition, but for participants who were disciplined harshly there was no difference between the oxytocin and placebo condition. Such effects were not found during listening to infant laughter. We conclude that early caregiving experiences constitute an important moderator of the prosocial and/or stress-reducing effects of oxytocin. Oxytocin administration may increase trust and cooperation in individuals with supportive backgrounds, but not generate this effect in individuals who as a consequence of unfavorable early caregiving experiences may have a bias toward negative interpretation of social cues.

The influence of oxytocin administration on responses to infant faces and potential moderation by OXTR genotype.

PubMed

Marsh, Abigail A; Yu, Henry H; Pine, Daniel S; Gorodetsky, Elena K; Goldman, David; Blair, R J R

2012-12-01

Oxytocin is a neuropeptide that is associated with increases in social affiliative behaviors, particularly toward infants. However, no previous study has investigated healthy adults' responses to infant faces following oxytocin administration. In addition, given that preliminary evidence suggests that a single-nucleotide polymorphism of the oxytocin receptor (OXTR) gene, rs53576, may influence behaviors associated with parental sensitivity, we assessed whether such responses vary according to OXTR rs53576 genotype. The present study assessed the effects of intranasally administered oxytocin and OXTR genotype on human adults' preferences for infant faces. A double-blind, between-groups design was used, with 57 genotyped volunteers randomly assigned to receive intranasally administered oxytocin or placebo. Fifty minutes following the administration of oxytocin or placebo, participants viewed infants' and adults' faces showing neutral expressions and assessed how appealing they found each face. Infants' faces were more strongly preferred following oxytocin inhalation relative to placebo. When participants were separated according to genotype, this effect was only observed for participants homozygous for the rs53576G allele. Parallel effects were not seen for adults' faces. The present results are consistent with the hypothesis that acute oxytocin administration increases sensitivity to reward-relevant features of infants and/or reduces sensitivity to their aversive properties. The results are also consistent with suggestions of more efficient oxytocinergic function in rs53576G homozygotes.

Examination of the Pharmacology of Oxytocin and Clinical Guidelines for Use in Labor.

PubMed

Page, Katie; McCool, William F; Guidera, Mamie

2017-07-01

The use of exogenous oxytocin to induce or augment labor has increased in recent years. This literature-informed review examines the action of this medication and the potential associated complications, with an evaluation of current professional practice guidelines. A brief history of the use of exogenous oxytocin for labor induction or augmentation is presented. In addition, risk management strategies for the prevention of oxytocin-related adverse outcomes and subsequent litigation are identified. © 2017 by the American College of Nurse-Midwives.

Pupil-mimicry conditions trust in partners: moderation by oxytocin and group membership

PubMed Central

De Dreu, Carsten K. W.

2017-01-01

Across species, oxytocin, an evolutionarily ancient neuropeptide, facilitates social communication by attuning individuals to conspecifics' social signals, fostering trust and bonding. The eyes have an important signalling function; and humans use their salient and communicative eyes to intentionally and unintentionally send social signals to others, by contracting the muscles around their eyes and pupils. In our earlier research, we observed that interaction partners with dilating pupils are trusted more than partners with constricting pupils. But over and beyond this effect, we found that the pupil sizes of partners synchronize and that when pupils synchronously dilate, trust is further boosted. Critically, this linkage between mimicry and trust was bound to interactions between ingroup members. The current study investigates whether these findings are modulated by oxytocin and sex of participant and partner. Using incentivized trust games with partners from ingroup and outgroup whose pupils dilated, remained static or constricted, this study replicates our earlier findings. It further reveals that (i) male participants withhold trust from partners with constricting pupils and extend trust to partners with dilating pupils, especially when given oxytocin rather than placebo; (ii) female participants trust partners with dilating pupils most, but this effect is blunted under oxytocin; (iii) under oxytocin rather than placebo, pupil dilation mimicry is weaker and pupil constriction mimicry stronger; and (iv) the link between pupil constriction mimicry and distrust observed under placebo disappears under oxytocin. We suggest that pupil-contingent trust is parochial and evolved in social species in and because of group life. PMID:28250181

Pupil-mimicry conditions trust in partners: moderation by oxytocin and group membership.

PubMed

Kret, Mariska E; De Dreu, Carsten K W

2017-03-15

Across species, oxytocin, an evolutionarily ancient neuropeptide, facilitates social communication by attuning individuals to conspecifics' social signals, fostering trust and bonding. The eyes have an important signalling function; and humans use their salient and communicative eyes to intentionally and unintentionally send social signals to others, by contracting the muscles around their eyes and pupils. In our earlier research, we observed that interaction partners with dilating pupils are trusted more than partners with constricting pupils. But over and beyond this effect, we found that the pupil sizes of partners synchronize and that when pupils synchronously dilate, trust is further boosted. Critically, this linkage between mimicry and trust was bound to interactions between ingroup members. The current study investigates whether these findings are modulated by oxytocin and sex of participant and partner. Using incentivized trust games with partners from ingroup and outgroup whose pupils dilated, remained static or constricted, this study replicates our earlier findings. It further reveals that (i) male participants withhold trust from partners with constricting pupils and extend trust to partners with dilating pupils, especially when given oxytocin rather than placebo; (ii) female participants trust partners with dilating pupils most, but this effect is blunted under oxytocin; (iii) under oxytocin rather than placebo, pupil dilation mimicry is weaker and pupil constriction mimicry stronger; and (iv) the link between pupil constriction mimicry and distrust observed under placebo disappears under oxytocin. We suggest that pupil-contingent trust is parochial and evolved in social species in and because of group life. © 2017 The Authors.

Oxytocin facilitation of acceptance of social advice is dependent upon the perceived trustworthiness of individual advisors.

PubMed

Luo, Ruixue; Xu, Lei; Zhao, Weihua; Ma, Xiaole; Xu, Xiaolei; Kou, Juan; Gao, Zhao; Becker, Benjamin; Kendrick, Keith M

2017-09-01

The neuropeptide oxytocin may increase social cohesion by making us more willing to trust others and/or to conform to their opinions. Here we investigated whether intranasal oxytocin can influence acceptance of advice given on solving everyday social problems by either individual expert (psychologist) or non-expert advisors with or without influencing their perceived likeability or trustworthiness. In a double-blind, between-subject, placebo-control design study in 160 male and female subjects, intranasal oxytocin (24IU) only significantly enhanced acceptance of advice given by female psychologists who were rated as the most trustworthy advisors. However, oxytocin itself did not alter either trustworthiness or likeability ratings. The oxytocin effect on acceptance of the female psychologist's advice was not maintained after a week, with subjects mainly reverting to their original solutions. These findings suggest that while oxytocin can transiently increase acceptance of advice from the most trustworthy individuals this is because it makes subjects more likely to conform to their opinions rather than enhancing their perceived trustworthiness or likeability. Thus in every day contexts oxytocin may primarily promote social cohesion by facilitating conformity towards the opinions of the most trusted individuals. Copyright © 2017. Published by Elsevier Ltd.

The effects of intranasal oxytocin on smoothie intake, cortisol and attentional bias in anorexia nervosa.

PubMed

Leppanen, Jenni; Cardi, Valentina; Ng, Kah Wee; Paloyelis, Yannis; Stein, Daniel; Tchanturia, Kate; Treasure, Janet

2017-05-01

Anorexia nervosa (AN) is characterised by severe malnutrition as well as intense fear and anxiety around food and eating with associated anomalies in information processing. Previous studies have found that the neuropeptide, oxytocin, can influence eating behaviour, lower the neurobiological stress response and anxiety among clinical populations, and alter attentional processing of food and eating related images in AN. Thirty adult women with AN and twenty-nine healthy comparison (HC) women took part in the current study. The study used double blind, placebo controlled, crossover design to investigate the effects of a single dose of intranasal oxytocin (40 IU) on a standard laboratory smoothie challenge, and on salivary cortisol, anxiety, and attentional bias towards food images before and after the smoothie challenge in AN and HC participants. Attentional bias was assessed using a visual probe task. Relative to placebo intranasal oxytocin reduced salivary cortisol and altered anomalies in attentional bias towards food images in the AN group only. The oxytocin-induced reduction in attentional avoidance of food images correlated with oxytocin induced reduction in salivary cortisol in the AN group before the smoothie challenge. Intranasal oxytocin did not significantly alter subjective feelings of anxiety or intake during the smoothie challenge in the AN or HC groups. Intranasal oxytocin may moderate the automated information processing biases in AN and reduce neurobiological stress. Further investigation of the effects of repeated administration of oxytocin on these processes as well as on eating behaviour and subjective anxiety would be of interest. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Associations between oxytocin receptor gene (OXTR) methylation, plasma oxytocin, and attachment across adulthood.

PubMed

Ebner, Natalie C; Lin, Tian; Muradoglu, Melis; Weir, Devon H; Plasencia, Gabriela M; Lillard, Travis S; Pournajafi-Nazarloo, Hossein; Cohen, Ronald A; Sue Carter, C; Connelly, Jessica J

2018-02-02

The neuropeptide oxytocin (OT) has been implicated in a wide range of affiliative processes. OT exerts its functions via OT receptors, which are encoded by the oxytocin receptor gene (OXTR). Epigenetic modification of OXTR through the process of DNA methylation has been associated with individual differences in behavioral phenotypes. Specifically, lower levels of OXTR methylation have been linked to better social and affective functioning. However, research on epigenetic mechanisms of OXTR is scarce in non-clinical populations, and even less is known about epigenetic variability across adulthood. The present study assessed methylation levels at OXTR CpG site -934 and plasma OT levels in 22 young (20-31 years, M = 23.6) and 34 older (63-80 years, M = 71.4) participants. Lower levels of OXTR methylation and higher plasma OT levels were associated with less self-reported attachment anxiety in young but not older participants, with largely independent contributions of OXTR methylation and plasma OT levels. In contrast, in the overall sample, lower levels of OXTR methylation were associated with higher self-reported attachment avoidance. Age analysis suggested that these results were largely driven by young adults. Plasma OT levels were unrelated to attachment avoidance. Taken together, these findings support the emerging notion in the literature that epigenetic properties of OXTR, in addition to endogenous OT levels, are related to adult attachment. Further, the age effects observed in the associations between OXTR methylation, plasma OT, and adult attachment emphasize the importance of adopting a developmental perspective when studying properties of the OT system and their relation to affiliative processes. Findings contribute to growing evidence suggesting that epigenetic modification of genes regulating OT pathways and endogenous OT levels are associated with the way people form and maintain intimate social relationships. Copyright © 2018 Elsevier B

Oxytocin-secreting system: A major part of the neuroendocrine center regulating immunologic activity.

PubMed

Wang, Ping; Yang, Hai-Peng; Tian, Shujun; Wang, Liwei; Wang, Stephani C; Zhang, Fengmin; Wang, Yu-Feng

2015-12-15

Interactions between the nervous system and immune system have been studied extensively. However, the mechanisms underlying the neural regulation of immune activity, particularly the neuroendocrine regulation of immunologic functions, remain elusive. In this review, we provide a comprehensive examination of current evidence on interactions between the immune system and hypothalamic oxytocin-secreting system. We highlight the fact that oxytocin may have significant effects in the body, beyond its classical functions in lactation and parturition. Similar to the hypothalamo-pituitary-adrenal axis, the oxytocin-secreting system closely interacts with classical immune system, integrating both neurochemical and immunologic signals in the central nervous system and in turn affects immunologic defense, homeostasis, and surveillance. Lastly, this review explores therapeutic potentials of oxytocin in treating immunologic disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

The Association between the Level of Plasma Oxytocin and Craving among Former Heroin Users.

PubMed

Lin, Shih-Hsien; Chen, Po See; Lee, Lan-Ting; Lee, Sheng-Yu; Tsai, Hsin Chun; Chen, Wei Tseng; Chen, Kao Chin; Lee, I Hui; Lu, Ru-Band; Yang, Yen Kuang

2018-06-14

Animal studies have demonstrated that oxytocin can influence addiction behaviors and might interact with the dopaminergic system, which is a key component of addiction behaviors. However, related evidence from clinical studies is scarce. The aim of our study was to explore the relationship between plasma oxytocin level and heroin craving among patients receiving methadone maintenance treatment, and to ascertain whether this relationship is moderated by novelty-seeking. The study was conducted in a methadone maintenance therapy clinic of a medical center in Taiwan. Seventy-seven patients with heroin addiction were enrolled. Plasma oxytocin was measured using an ELISA kit. Craving was assessed using an established instrument, the Chinese Craving Scale. A significant negative association was found between the plasma oxytocin level and craving score, which remained robust after controlling the effects of social support and low-density lipoprotein cholesterol. An interaction between oxytocin and novelty-seeking indicated that this relationship was stronger among patients with a lower level of novelty-seeking. This finding may be taken into account in future studies and may provide a basis for the development of potential treatment for addiction. The effect of oxytocin for the treatment of opioid dependence might be modulated by some psychological factors. © 2018 S. Karger AG, Basel.

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

ERIC Educational Resources Information Center

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…

Oxytocin effects on mind-reading are moderated by experiences of maternal love withdrawal: an fMRI study.

PubMed

Riem, Madelon M E; Bakermans-Kranenburg, Marian J; Voorthuis, Alexandra; van IJzendoorn, Marinus H

2014-06-03

The neuropeptide oxytocin has been shown to stimulate a range of social behaviors. However, recent studies indicate that the effects of intranasal oxytocin are more nuanced than previously thought and that contextual factors and individual characteristics moderate the beneficiary oxytocin effects. In this randomized-controlled trial we examine the influence of intranasally administered oxytocin on neural activity during mind-reading with fMRI, taking into account harsh caregiving experiences as a potential moderator. Participants were 50 women who received a nasal spray containing either 16 IU of oxytocin or a placebo and had reported how often their mother used love withdrawal as a disciplinary strategy. Participants performed an adapted version of the Reading the Mind in the Eyes Test (RMET), a task which requires individuals to infer mental states by looking at photographs of the eye region of faces. We found that oxytocin enhanced neural activation in the superior temporal gyrus (STG) and insula during the RMET. Moreover, oxytocin increased RMET performance outside the scanner. However, the oxytocin induced changes in STG activation and RMET performance were only brought about in potentially less socially proficient individuals who had low RMET performance, that is, participants reporting higher levels of maternal love withdrawal. Copyright © 2014 Elsevier Inc. All rights reserved.

Emotional maltreatment is associated with atypical responding to stimulation of endogenous oxytocin release through mechanically-delivered massage in males.

PubMed

Riem, Madelon M E; De Carli, Pietro; van IJzendoorn, Marinus H; Linting, Marielle; Grewen, Karen M; Bakermans-Kranenburg, Marian J

2017-11-01

The neuropeptide oxytocin plays an important role in social behavior, parenting, and affectionate touch and there is some evidence that oxytocin release can be stimulated by massage or affectionate touch. We examined the effects of massage applied by a massage seat cover on salivary oxytocin levels in two exploratory studies using within-subject designs. In Study 1 massage effects on oxytocin levels were examined in a sample of N=20 healthy female participants. Effects of a 15-min massage session were compared to a control condition during which participants sat on a comfortable chair without a massage seat cover. Salivary oxytocin levels were measured at baseline and up to three hours after the session. We found that massage attenuated oxytocin decreases over time, indicating that massage stimulates oxytocin release. In Study 2, we examined whether effects of massage in N=46 healthy male participants depend on experiences of emotional maltreatment. In addition, we examined whether enhanced oxytocin levels after massage affect the use of excessive handgrip force in response to infant crying and laughter as measured with a handgrip dynamometer. Our findings show that massage results in elevated oxytocin levels compared to a control condition, but that the effects of massage are dependent on experiences of emotional maltreatment. Men with experiences of emotional maltreatment showed lower oxytocin levels, which did not increase after massage. Furthermore, we found that high oxytocin levels after massage were related to reduced handgrip force during exposure to infant crying and laughter, indicating that massage stimulates a sensitive response to infant signals by stimulating oxytocin release. Although massage did not affect oxytocin levels in individuals with experiences of maltreatment, it reduced the use of handgrip force in response to infant crying and laughter in these individuals. Our findings indicate that emotional maltreatment is associated with atypical

Perception of social interaction compresses subjective duration in an oxytocin-dependent manner

PubMed Central

2018-01-01

Communication through body gestures permeates our daily life. Efficient perception of the message therein reflects one’s social cognitive competency. Here we report that such competency is manifested temporally as shortened subjective duration of social interactions: motion sequences showing agents acting communicatively are perceived to be significantly shorter in duration as compared with those acting noncommunicatively. The strength of this effect is negatively correlated with one’s autistic-like tendency. Critically, intranasal oxytocin administration restores the temporal compression effect in socially less proficient individuals, whereas the administration of atosiban, a competitive antagonist of oxytocin, diminishes the effect in socially proficient individuals. These findings indicate that perceived time, rather than being a faithful representation of physical time, is highly idiosyncratic and ingrained with one’s personality trait. Moreover, they suggest that oxytocin is involved in mediating time perception of social interaction, further supporting the role of oxytocin in human social cognition. PMID:29784084

Perception of social interaction compresses subjective duration in an oxytocin-dependent manner.

PubMed

Liu, Rui; Yuan, Xiangyong; Chen, Kepu; Jiang, Yi; Zhou, Wen

2018-05-22

Communication through body gestures permeates our daily life. Efficient perception of the message therein reflects one's social cognitive competency. Here we report that such competency is manifested temporally as shortened subjective duration of social interactions: motion sequences showing agents acting communicatively are perceived to be significantly shorter in duration as compared with those acting noncommunicatively. The strength of this effect is negatively correlated with one's autistic-like tendency. Critically, intranasal oxytocin administration restores the temporal compression effect in socially less proficient individuals, whereas the administration of atosiban, a competitive antagonist of oxytocin, diminishes the effect in socially proficient individuals. These findings indicate that perceived time, rather than being a faithful representation of physical time, is highly idiosyncratic and ingrained with one's personality trait. Moreover, they suggest that oxytocin is involved in mediating time perception of social interaction, further supporting the role of oxytocin in human social cognition. © 2018, Liu et al.

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

PubMed Central

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

2009-01-01

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. PMID:19934046

Lack of Association between Human Plasma Oxytocin and Interpersonal Trust in a Prisoners Dilemma Paradigm

DTIC Science & Technology

2014-12-30

light of these findings, previous published work that used oxytocin immunoassays without sample extraction should be reexamined and future research... immunoassays without sample extraction should be reexamined and future research exploring links between endogenous human oxytocin and trust or social...oxytocin are likely associated with hypothalamic production and release, but the gastrointestinal tract, heart, uterus, testes , corpus luteum, and placenta

Oxytocin influences processing of socially relevant cues in the ventral tegmental area of the human brain.

PubMed

Groppe, Sarah E; Gossen, Anna; Rademacher, Lena; Hahn, Alexa; Westphal, Luzie; Gründer, Gerhard; Spreckelmeyer, Katja N

2013-08-01

Evidence accumulates that the neuropeptide oxytocin plays an important role in mediating social interaction among humans and that a dysfunction in oxytocin-modulated brain mechanisms might lie at the core of disturbed social behavior in neuropsychiatric disease. Explanatory models suggest that oxytocin guides social approach and avoidance by modulating the perceived salience of socially meaningful cues. Animal data point toward the ventral tegmental area (VTA) as the brain site where this modulation takes place. We used functional magnetic resonance imaging and a social incentive delay task to test the hypothesis that oxytocin modulates the neural processing of socially relevant cues in the VTA, hereby facilitating behavioral response. Twenty-eight nulliparous women (not taking any hormones) received intranasal oxytocin or placebo in a double-blind randomized clinical trial with a parallel-group design. Oxytocin significantly enhanced VTA activation in response to cues signaling social reward (friendly face) or social punishment (angry face). Oxytocin effects on behavioral performance were modulated by individual differences in sociability with enhanced performance in women scoring low but decreased performance in women scoring high on self-reported measures of agreeableness. Our data provide evidence that the VTA is the human brain site where oxytocin attaches salience to socially relevant cues. This mechanism might play an important role in triggering motivation to react at the prospect of social reward or punishment. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Oxytocin administration selectively improves olfactory detection thresholds for lyral in patients with schizophrenia

PubMed Central

Woolley, J.D.; Lam, O.; Chuang, B.; Ford, J.M.; Mathalon, D.H.; Vinogradov, S.

2015-01-01

Summary Background Olfaction plays an important role in mammalian social behavior. Olfactory deficits are common in schizophrenia and correlate with negative symptoms and low social drive. Despite their prominence and possible clinical relevance, little is understood about the pathological mechanisms underlying olfactory deficits in schizophrenia and there are currently no effective treatments for these deficits. The prosocial neuropeptide oxytocin may affect the olfactory system when administered intranasally to humans and there is growing interest in its therapeutic potential in schizophrenia. Methods To examine this model, we administered 40 IU of oxytocin and placebo intranasally to 31 patients with a schizophrenia spectrum illness and 34 age-matched healthy control participants in a randomized, double-blind, placebo-controlled, cross-over study. On each test day, participants completed an olfactory detection threshold test for two different odors: (1) lyral, a synthetic fragrance compound for which patients with schizophrenia have specific olfactory detection threshold deficits, possibly related to decreased cyclic adenosine 3′,5′-monophosphate (cAMP) signaling; and (2) anise, a compound for which olfactory detection thresholds change with menstrual cycle phase in women. Results On the placebo test day, patients with schizophrenia did not significantly differ from healthy controls in detection of either odor. We found that oxytocin administration significantly and selectively improved olfactory detection thresholds for lyral but not for anise in patients with schizophrenia. In contrast, oxytocin had no effect on detection of either odor in healthy controls. Discussion Our data indicate that oxytocin administration may ameliorate olfactory deficits in schizophrenia and suggest the effects of intranasal oxytocin may extend to influencing the olfactory system. Given that oxytocin has been found to increase cAMP signaling in vitro a possible mechanism for

Oxytocin administration selectively improves olfactory detection thresholds for lyral in patients with schizophrenia.

PubMed

Woolley, J D; Lam, O; Chuang, B; Ford, J M; Mathalon, D H; Vinogradov, S

2015-03-01

Olfaction plays an important role in mammalian social behavior. Olfactory deficits are common in schizophrenia and correlate with negative symptoms and low social drive. Despite their prominence and possible clinical relevance, little is understood about the pathological mechanisms underlying olfactory deficits in schizophrenia and there are currently no effective treatments for these deficits. The prosocial neuropeptide oxytocin may affect the olfactory system when administered intranasally to humans and there is growing interest in its therapeutic potential in schizophrenia. To examine this model, we administered 40IU of oxytocin and placebo intranasally to 31 patients with a schizophrenia spectrum illness and 34 age-matched healthy control participants in a randomized, double-blind, placebo-controlled, cross-over study. On each test day, participants completed an olfactory detection threshold test for two different odors: (1) lyral, a synthetic fragrance compound for which patients with schizophrenia have specific olfactory detection threshold deficits, possibly related to decreased cyclic adenosine 3',5'-monophosphate (cAMP) signaling; and (2) anise, a compound for which olfactory detection thresholds change with menstrual cycle phase in women. On the placebo test day, patients with schizophrenia did not significantly differ from healthy controls in detection of either odor. We found that oxytocin administration significantly and selectively improved olfactory detection thresholds for lyral but not for anise in patients with schizophrenia. In contrast, oxytocin had no effect on detection of either odor in healthy controls. Our data indicate that oxytocin administration may ameliorate olfactory deficits in schizophrenia and suggest the effects of intranasal oxytocin may extend to influencing the olfactory system. Given that oxytocin has been found to increase cAMP signaling in vitro a possible mechanism for these effects is discussed. Published by Elsevier Ltd.

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

PubMed

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.

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

PubMed

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.

State-Space Formulation for Circuit Analysis

ERIC Educational Resources Information Center

Martinez-Marin, T.

2010-01-01

This paper presents a new state-space approach for temporal analysis of electrical circuits. The method systematically obtains the state-space formulation of nondegenerate linear networks without using concepts of topology. It employs nodal/mesh systematic analysis to reduce the number of undesired variables. This approach helps students to…

The effect of oxytocin on human-directed social behaviour in dogs (Canis familiaris).

PubMed

Kis, Anna; Ciobica, Alin; Topál, József

2017-08-01

The oxytocin system has recently received increasing attention due to its effect on complex human behaviours. In parallel to this, over the past couple of decades, the human-analogue social behaviour of dogs has been intensively studied. Combining these two lines of research (e.g. studying the relationship between dog social behaviour and the oxytocin system) is a promising new research area. The present paper reviews the existing literature on how oxytocin is related to different aspects of human-directed social behaviour in dogs. Copyright © 2017 Elsevier Inc. All rights reserved.

The effects of oxytocin and atosiban on the modulation of heart rate in pregnant women.

PubMed

Weissman, Amir; Tobia, Rana Swed; Burke, Yechiel Z; Maxymovski, Olga; Drugan, Arie

2017-02-01

To evaluate autonomic modulation of heart rate in pregnant women treated with oxytocin to induce labor and with atosiban (an oxytocin antagonist) to arrest preterm labor. A prospective study with two cohorts: 14 pregnant women treated with atosiban for premature uterine contractions, and 28 women undergoing induction of labor with oxytocin. Computerized analyses of the electrocardiogram were performed with spectral and nonlinear dynamic analyses. Atosiban did not alter any of the variables associated with heart rate variability, whereas oxytocin showed a dose-dependent decrease in heart rate (p < 0.05) and a significant increase in all spectral variables studied (p < 0.01). Atosiban has no adverse effects on the cardiovascular system or the modulation of heart rate. Oxytocin, on the other hand, can cause a dose-dependent bradycardic effect and an increase in the spectral power, thus should be used with caution in certain pregnant women.

Oxytocin Secretion Is Associated with Severity of Disordered Eating Psychopathology and Insular Cortex Hypoactivation in Anorexia Nervosa

PubMed Central

Holsen, Laura M.; Santin, McKale; Meenaghan, Erinne; Eddy, Kamryn T.; Becker, Anne E.; Herzog, David B.; Goldstein, Jill M.; Klibanski, Anne

2012-01-01

Context: Animal data suggest that oxytocin is a satiety hormone. We have demonstrated that anorexia nervosa (anorexia), a disorder characterized by food restriction, low weight, and hypoleptinemia, is associated with decreased nocturnal oxytocin secretion. We have also reported functional magnetic resonance imaging (fMRI) hypoactivation in anorexia in brain regions involved in food motivation. The relationships between oxytocin, food-motivation neurocircuitry, and disordered eating psychopathology have not been investigated in humans. Objective: The objective of the study was to determine whether the oxytocin response to feeding in anorexia differs from healthy women and to establish the relationship between oxytocin secretion and disordered eating psychopathology and food-motivation neurocircuitry. Design: This was a cross-sectional study. Setting: The study was conducted at a clinical research center. Participants: Participants included 35 women: 13 anorexia (AN), nine weight-recovered anorexia (ANWR), and 13 healthy controls (HC). Measures: Peripheral oxytocin and leptin levels were measured fasting and 30, 60, and 120 min after a standardized mixed meal. The Eating Disorder Examination-Questionnaire was used to assess disordered eating psychopathology. fMRI was performed during visual processing of food and nonfood stimuli to measure brain activation before and after the meal. Results: Mean oxytocin levels were higher in AN than HC at 60 and 120 min and lower in ANWR than HC at 0, 30, and 120 min and AN at all time points. Mean oxytocin area under the curve (AUC) was highest in AN, intermediate in HC, and lowest in ANWR. Mean leptin levels at all time points and AUC were lower in AN than HC and ANWR. Oxytocin AUC was associated with leptin AUC in ANWR and HC but not in AN. Oxytocin AUC was associated with the severity of disordered eating psychopathology in AN and ANWR, independent of leptin secretion, and was associated with between-group variance in f

Oxytocin decreases aversion to angry faces in an associative learning task.

PubMed

Evans, Simon; Shergill, Sukhwinder S; Averbeck, Bruno B

2010-12-01

Social and financial considerations are often integrated when real life decisions are made, and recent studies have provided evidence that similar brain networks are engaged when either social or financial information is integrated. Other studies, however, have suggested that the neuropeptide oxytocin can specifically affect social behaviors, which would suggest separable mechanisms at the pharmacological level. Thus, we examined the hypothesis that oxytocin would specifically affect social and not financial information in a decision making task, in which participants learned which of the two faces, one smiling and the other angry or sad, was most often being rewarded. We found that oxytocin specifically decreased aversion to angry faces, without affecting integration of positive or negative financial feedback or choices related to happy vs sad faces.

Research review: Social motivation and oxytocin in autism--implications for joint attention development and intervention.

PubMed

Stavropoulos, Katherine K M; Carver, Leslie J

2013-06-01

The social motivation hypothesis (SMH) suggests that individuals with autism spectrum disorders (ASD) are less intrinsically rewarded by social stimuli than their neurotypical peers. This difference in social motivation has been posited as a factor contributing to social deficits in ASD. Social motivation is thought to involve the neuropeptide oxytocin. Here, we review the evidence for oxytocin effects in ASD, and discuss its potential role in one important social cognitive behavior. Systematic searches were conducted using the PsychINFO and MEDLINE databases and the search terms 'oxytocin' and 'autism'; the same databases were used for separate searches for 'joint attention', 'intervention', and 'autism', using the same inclusion criteria as an earlier 2011 review but updating it for the period 2010 to October 2012. Several studies suggest that giving oxytocin to both individuals with ASD and neurotypical individuals can enhance performance on social cognitive tasks. Studies that have attempted to intervene in joint attention in ASD suggest that social motivation may be a particular obstacle to lasting effects. The review of the evidence for the SMH suggests a potential role for oxytocin in social motivation deficits in ASD. Because of its importance for later communicative and social development, the focus here is on implications of oxytocin and social motivation in the development of and interventions in joint attention. Joint attention is a central impairment in ASD, and as a result is the focus of several behavioral interventions. In describing this previous research on joint attention interventions in ASD, we pay particular attention to problems encountered in such studies, and propose ways that oxytocin may facilitate behavioral intervention in this area. For future research, integrating behavioral and pharmacological interventions (oxytocin administration) would be a worthwhile experimental direction to improve understanding of the role of oxytocin in ASD

Intranasal Oxytocin to Prevent Posttraumatic Stress Disorder Symptoms: A Randomized Controlled Trial in Emergency Department Patients.

PubMed

van Zuiden, Mirjam; Frijling, Jessie L; Nawijn, Laura; Koch, Saskia B J; Goslings, J Carel; Luitse, Jan S; Biesheuvel, Tessa H; Honig, Adriaan; Veltman, Dick J; Olff, Miranda

2017-06-15

There are currently few preventive interventions available for posttraumatic stress disorder (PTSD). Intranasal oxytocin administration early after trauma may prevent PTSD, because oxytocin administration was previously found to beneficially impact PTSD vulnerability factors, including neural fear responsiveness, peripheral stress reactivity, and socioemotional functioning. Therefore, we investigated the effects of intranasal oxytocin administration early after trauma on subsequent clinician-rated PTSD symptoms. We then assessed whether baseline characteristics moderated the intervention's effects. We performed a multicenter, randomized, double-blind, placebo-controlled clinical trial. Adult emergency department patients with moderate to severe acute distress (n = 120; 85% accident victims) were randomized to intranasal oxytocin (8 days/40 IU twice daily) or placebo (8 days/10 puffs twice daily), initiated within 12 days posttrauma. The Clinician-Administered PTSD Scale (CAPS) was administered at baseline (within 10 days posttrauma) and at 1.5, 3, and 6 months posttrauma. The intention-to-treat sample included 107 participants (oxytocin: n = 53; placebo: n = 54). We did not observe a significant group difference in CAPS total score at 1.5 months posttrauma (primary outcome) or across follow-up (secondary outcome). Secondary analyses showed that participants with high baseline CAPS scores receiving oxytocin had significantly lower CAPS scores across follow-up than participants with high baseline CAPS scores receiving placebo. Oxytocin administration early after trauma did not attenuate clinician-rated PTSD symptoms in all trauma-exposed participants with acute distress. However, participants with high acute clinician-rated PTSD symptom severity did show beneficial effects of oxytocin. Although replication is warranted, these findings suggest that oxytocin administration is a promising preventive intervention for PTSD for individuals with high acute PTSD symptoms

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

PubMed

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.

Chronic fluoxetine inhibits sexual behavior in the male rat: reversal with oxytocin.

PubMed

Cantor, J M; Binik, Y M; Pfaus, J G

1999-06-01

Selective serotonin reuptake inhibitors, used widely in the treatment of depression, progressively inhibit sexual orgasm in many patients and induce a transient inhibition of sexual desire. We attempted to model the effects of these drugs in sexually experienced male rats during tests of copulation in bilevel chambers. These chambers allow the study of both appetitive and consummatory sexual responses of male rats. Males were treated daily with fluoxetine hydrochloride (0, 1, 5, or 10 mg/kg) and tested for sexual behavior with receptive females at 4-day intervals. Rats were treated with oxytocin (200 ng/kg) or saline after ejaculations had decreased. Fluoxetine decreased ejaculatory responses of male rats in a dose- and time-dependent fashion, but left the copulatory efficiency of the males intact. In contrast, conditioned level changing, a measure of appetitive sexual excitement, was inhibited following acute and chronic treatment with 10 mg/kg, although tolerance may have developed to the effect of 5 mg/kg. Subsequent administration of oxytocin restored the ejaculatory response but not the measure of sexual excitement to baseline levels. The reversal by oxytocin of the fluoxetine-induced deficit in ejaculations is consistent with the hypothesis that serotonin suppresses ejaculatory mechanisms by interrupting the action of oxytocin, which normally accompanies sexual behavior. Co-administration of oxytocin may help to alleviate the predominant sexual side effect of serotonin reuptake blockers.

Intranasal administration of oxytocin increases compassion toward women

PubMed Central

Palgi, Sharon; Klein, Ehud

2015-01-01

It has been suggested that the degree of compassion—the feeling of warmth, understanding and kindness that motivates the desire to help others, is modulated by observers’ views regarding the target’s vulnerability and suffering. This study tested the hypothesis that as compassion developed to protect vulnerable kinships, hormones such as oxytocin, which have been suggested as playing a key role in ‘tend-and-befriend’ behaviors among women, will enhance compassion toward women but not toward men. Thirty subjects participated in a double-blind, placebo-controlled, within-subject study. Following administration of oxytocin/placebo, participants listened to recordings of different female/male protagonists describing distressful emotional conflicts and were then asked to provide compassionate advice to the protagonist. The participants’ responses were coded according to various components of compassion by two clinical psychologists who were blind to the treatment. The results showed that in women and men participants oxytocin enhanced compassion toward women, but did not affect compassion toward men. These findings indicate that the oxytocinergic system differentially mediates compassion toward women and toward men, emphasizing an evolutionary perspective that views compassion as a caregiving behavior designed to help vulnerable individuals. PMID:24711542

Maternal Oxytocin Is Linked to Close Mother-Infant Proximity in Grey Seals (Halichoerus grypus)

PubMed Central

Robinson, Kelly J.; Twiss, Sean D.; Hazon, Neil; Pomeroy, Patrick P.

2015-01-01

Maternal behaviour is a crucial component of reproduction in all mammals; however the quality of care that mothers give to infants can vary greatly. It is vital to document variation in maternal behaviour caused by the physiological processes controlling its expression. This underlying physiology should be conserved throughout reproductive events and should be replicated across all individuals of a species; therefore, any correlates to maternal care quality may be present across many individuals or contexts. Oxytocin modulates the initiation and expression of maternal behaviour in mammals; therefore we tested whether maternal plasma oxytocin concentrations correlated to key maternal behaviours in wild grey seals (Halichoerus grypus). Plasma oxytocin concentrations in non-breeding individuals (4.3 ±0.5 pg/ml) were significantly lower than those in mothers with dependent pups in both early (8.2 ±0.8 pg/ml) and late (6.9 ±0.7 pg/ml) lactation. Maternal plasma oxytocin concentrations were not correlated to the amount of nursing prior to sampling, or a mother’s nursing intensity throughout the dependant period. Mothers with high plasma oxytocin concentrations stayed closer to their pups, reducing the likelihood of mother-pup separation during lactation which is credited with causing starvation, the largest cause of pup mortality in grey seals. This is the first study to link endogenous oxytocin concentrations in wild mammalian mothers with any type of maternal behaviour. Oxytocin’s structure and function is widely conserved across mammalian mothers, including humans. Defining the impact the oxytocin system has on maternal behaviour highlights relationships that may occur across many individuals or species, and such behaviours heavily influence infant development and an individual’s lifetime reproductive success. PMID:26698856

Oxytocin enhances attentional bias for neutral and positive expression faces in individuals with higher autistic traits.

PubMed

Xu, Lei; Ma, Xiaole; Zhao, Weihua; Luo, Lizhu; Yao, Shuxia; Kendrick, Keith M

2015-12-01

There is considerable interest in the potential therapeutic role of the neuropeptide oxytocin in altering attentional bias towards emotional social stimuli in psychiatric disorders. However, it is still unclear whether oxytocin primarily influences attention towards positive or negative valence social stimuli. Here in a double-blind, placebo controlled, between subject design experiment in 60 healthy male subjects we have used the highly sensitive dual-target rapid serial visual presentation (RSVP) paradigm to investigate whether intranasal oxytocin (40IU) treatment alters attentional bias for emotional faces. Results show that oxytocin improved recognition accuracy of neutral and happy expression faces presented in the second target position (T2) during the period of reduced attentional capacity following prior presentation of a first neutral face target (T1), but had no effect on recognition of negative expression faces (angry, fearful, sad). Oxytocin also had no effect on recognition of non-social stimuli (digits) in this task. Recognition accuracy for neutral faces at T2 was negatively associated with autism spectrum quotient (ASQ) scores in the placebo group, and oxytocin's facilitatory effects were restricted to a sub-group of subjects with higher ASQ scores. Our results therefore indicate that oxytocin primarily enhances the allocation of attentional resources towards faces expressing neutral or positive emotion and does not influence that towards negative emotion ones or non-social stimuli. This effect of oxytocin is strongest in healthy individuals with higher autistic trait scores, thereby providing further support for its potential therapeutic use in autism spectrum disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nasal Oxytocin for Social Deficits in Childhood Autism: A Randomized Controlled Trial

ERIC Educational Resources Information Center

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…

Coming Full Circle: Contributions of Central and Peripheral Oxytocin Actions to Energy Balance

PubMed Central

Blevins, James E.

2013-01-01

The neuropeptide oxytocin has emerged as an important anorexigen in the regulation of energy balance. Its effects on food intake have largely been attributed to limiting meal size through interactions in key regulatory brain regions such as the hypothalamus and hindbrain. Pharmacologic and pair-feeding studies indicate that its ability to reduce body mass extends beyond that of food intake, affecting multiple factors that determine energy balance such as energy expenditure, lipolysis, and glucose regulation. Systemic administration of oxytocin recapitulates many of its effects when administered centrally, raising the questions of whether and to what extent circulating oxytocin contributes to energy regulation. Its therapeutic potential to treat metabolic conditions remains to be determined, but data from diet-induced and genetically obese rodent models as well as application of oxytocin in humans in other areas of research have revealed promising results thus far. PMID:23270805

Neuropeptide S Activates Paraventricular Oxytocin Neurons to Induce Anxiolysis.

PubMed

Grund, Thomas; Goyon, Stephanie; Li, Yuting; Eliava, Marina; Liu, Haikun; Charlet, Alexandre; Grinevich, Valery; Neumann, Inga D

2017-12-13

Neuropeptides, such as neuropeptide S (NPS) and oxytocin (OXT), represent potential options for the treatment of anxiety disorders due to their potent anxiolytic profile. In this study, we aimed to reveal the mechanisms underlying the behavioral action of NPS, and present a chain of evidence that the effects of NPS within the hypothalamic paraventricular nucleus (PVN) are mediated via actions on local OXT neurons in male Wistar rats. First, retrograde studies identified NPS fibers originating in the brainstem locus coeruleus, and projecting to the PVN. FACS identified prominent NPS receptor expression in PVN-OXT neurons. Using genetically encoded calcium indicators, we further demonstrated that NPS reliably induces a transient increase in intracellular Ca 2+ concentration in a subpopulation of OXT neurons, an effect mediated by NPS receptor. In addition, intracerebroventricular (i.c.v.) NPS evoked a significant somatodendritic release of OXT within the PVN as assessed by microdialysis in combination with a highly sensitive radioimmunoassay. Finally, we could show that the anxiolytic effect of NPS seen after i.c.v. or intra-PVN infusion requires responsive OXT neurons of the PVN and locally released OXT. Thus, pharmacological blockade of OXT receptors as well as chemogenetic silencing of OXT neurons within the PVN prevented the effect of synthetic NPS. In conclusion, our results indicate a significant role of the OXT system in mediating the effects of NPS on anxiety, and fill an important gap in our understanding of brain neuropeptide interactions in the context of regulation of emotional behavior within the hypothalamus. SIGNIFICANCE STATEMENT Given the rising scientific interest in neuropeptide research in the context of emotional and stress-related behaviors, our findings demonstrate a novel intrahypothalamic mechanism involving paraventricular oxytocin neurons that express the neuropeptide S receptor. These neurons respond with transient Ca 2+ increase and

The clinical and economic impact of nurse to patient staffing ratios in women receiving intrapartum oxytocin.

PubMed

Clark, Steven L; Saade, George A; Meyers, Janet A; Frye, Donna R; Perlin, Jonathan B

2014-02-01

To examine the relationship between nurse-to-patient staffing ratios and perinatal outcomes in women receiving oxytocin during labor. A retrospective analysis of perinatal outcomes in women receiving oxytocin for induction or augmentation of labor during 2010. Outcomes examined were fetal distress, birth asphyxia, primary cesarean delivery, chorioamnionitis, endomyometritis, and a composite of adverse events. Frequency of 1:1 nurse-to-patient staffing was determined for each hospital. Outcomes were compared between hospitals categorized into quartiles of staffing ratios. In 208,033 women delivering during 2010, there was no relation between frequency of 1:1 nurse-to-patient staffing ratio and improved perinatal outcomes. Adoption of universal 1:1 staffing in the United States would result in the need for an additional 27,000 labor nurses and a cost of $1.6 billion. Available data do not support the imposition of mandatory 1:1 nurse-to-patient staffing ratios for women receiving oxytocin in all U.S. facilities. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Oxytocin and autism: a systematic review of randomized controlled trials.

PubMed

Preti, Antonio; Melis, Mariangela; Siddi, Sara; Vellante, Marcello; Doneddu, Giuseppe; Fadda, Roberta

2014-03-01

Little is known about the effectiveness of pharmacological interventions on autism spectrum disorder (ASD). This is a systematic review of the randomized controlled trials (RCTs) of oxytocin interventions in autism, made from January 1990 to September 2013. A search of computerized databases was supplemented by manual search in the bibliographies of key publications. The methodological quality of the studies included in the review was evaluated independently by two researchers, according to a set of formal criteria. Discrepancies in scoring were resolved through discussion. The review yielded seven RCTs, including 101 subjects with ASD (males=95) and 8 males with Fragile X syndrome. The main categories of target symptoms tested in the studies were repetitive behaviors, eye gaze, and emotion recognition. The studies had a medium to high risk of bias. Most studies had small samples (median=15). All the studies but one reported statistically significant between-group differences on at least one outcome variable. Most findings were characterized by medium effect size. Only one study had evidence that the improvement in emotion recognition was maintained after 6 weeks of treatment with intranasal oxytocin. Overall, oxytocin was well tolerated and side effects, when present, were generally rated as mild; however, restlessness, increased irritability, and increased energy occurred more often under oxytocin. RCTs of oxytocin interventions in autism yielded potentially promising findings in measures of emotion recognition and eye gaze, which are impaired early in the course of the ASD condition and might disrupt social skills learning in developing children. There is a need for larger, more methodologically rigorous RCTs in this area. Future studies should be better powered to estimate outcomes with medium to low effect size, and should try to enroll female participants, who were rarely considered in previous studies. Risk of bias should be minimized. Human long

Integrated Formulation of Beacon-Based Exception Analysis for Multimissions

NASA Technical Reports Server (NTRS)

Mackey, Ryan; James, Mark; Park, Han; Zak, Mickail

2003-01-01

Further work on beacon-based exception analysis for multimissions (BEAM), a method of real-time, automated diagnosis of a complex electromechanical systems, has greatly expanded its capability and suitability of application. This expanded formulation, which fully integrates physical models and symbolic analysis, is described. The new formulation of BEAM expands upon previous advanced techniques for analysis of signal data, utilizing mathematical modeling of the system physics, and expert-system reasoning,

Effects of intranasal oxytocin on the neural basis of face processing in autism spectrum disorder.

PubMed

Domes, Gregor; Heinrichs, Markus; Kumbier, Ekkehardt; Grossmann, Annette; Hauenstein, Karlheinz; Herpertz, Sabine C

2013-08-01

Autism spectrum disorder (ASD) is associated with altered face processing and decreased activity in brain regions involved in face processing. The neuropeptide oxytocin has been shown to promote face processing and modulate brain activity in healthy adults. The present study examined the effects of oxytocin on the neural basis of face processing in adults with Asperger syndrome (AS). A group of 14 individuals with AS and a group of 14 neurotypical control participants performed a face-matching and a house-matching task during functional magnetic resonance imaging. The effects of a single dose of 24 IU intranasally administered oxytocin were tested in a randomized, placebo-controlled, within-subject, cross-over design. Under placebo, the AS group showed decreased activity in the right amygdala, fusiform gyrus, and inferior occipital gyrus compared with the control group during face processing. After oxytocin treatment, right amygdala activity to facial stimuli increased in the AS group. These findings indicate that oxytocin increases the saliency of social stimuli and in ASD and suggest that oxytocin might promote face processing and eye contact in individuals with ASD as prerequisites for neurotypical social interaction. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Oxytocin Motivates Non-Cooperation in Intergroup Conflict to Protect Vulnerable In-Group Members

PubMed Central

De Dreu, Carsten K. W.; Shalvi, Shaul; Greer, Lindred L.; Van Kleef, Gerben A.; Handgraaf, Michel J. J.

2012-01-01

Intergroup conflict is often driven by an individual's motivation to protect oneself and fellow group members against the threat of out-group aggression, including the tendency to pre-empt out-group threat through a competitive approach. Here we link such defense-motivated competition to oxytocin, a hypothalamic neuropeptide involved in reproduction and social bonding. An intergroup conflict game was developed to disentangle whether oxytocin motivates competitive approach to protect (i) immediate self-interest, (ii) vulnerable in-group members, or (iii) both. Males self-administered oxytocin or placebo (double-blind placebo-controlled) and made decisions with financial consequences to themselves, their fellow in-group members, and a competing out-group. Game payoffs were manipulated between-subjects so that non-cooperation by the out-group had high vs. low impact on personal payoff (personal vulnerability), and high vs. low impact on payoff to fellow in-group members (in-group vulnerability). When personal vulnerability was high, non-cooperation was unaffected by treatment and in-group vulnerability. When personal vulnerability was low, however, in-group vulnerability motivated non-cooperation but only when males received oxytocin. Oxytocin fuels a defense-motivated competitive approach to protect vulnerable group members, even when personal fate is not at stake. PMID:23144787

Amygdala response to negative images in postpartum vs nulliparous women and intranasal oxytocin.

PubMed

Rupp, Heather A; James, Thomas W; Ketterson, Ellen D; Sengelaub, Dale R; Ditzen, Beate; Heiman, Julia R

2014-01-01

The neuroendocrine state of new mothers may alter their neural processing of stressors in the environment through modulatory actions of oxytocin on the limbic system. We predicted that amygdala sensitivity to negatively arousing stimuli would be suppressed in postpartum compared to nulliparous women and that this suppression would be modulated by administration of oxytocin nasal spray. We measured brain activation (fMRI) and subjective arousal in response to negatively arousing pictures in 29 postpartum and 30 nulliparous women who received either oxytocin nasal spray or placebo before scanning. Pre- and post-exposure urinary cortisol levels were also measured. Postpartum women (placebo) demonstrated lower right amygdala activation in response to negative images, lower cortisol and lower negative photo arousal ratings to nulliparous women. Nulliparous women receiving oxytocin had lower right amygdala activation compared to placebo. Cortisol levels in the placebo group, and ratings of arousal across all women, were positively associated with right amygdala activation. Together, these findings demonstrate reductions in both amygdala activation and subjective negative arousal in untreated postpartum vs nulliparous women, supporting the hypothesis of an attenuated neural response to arousing stimuli in postpartum women. A causal role of oxytocin and the timing of potential effects require future investigation.

Oxytocin motivates non-cooperation in intergroup conflict to protect vulnerable in-group members.

PubMed

De Dreu, Carsten K W; Shalvi, Shaul; Greer, Lindred L; Van Kleef, Gerben A; Handgraaf, Michel J J

2012-01-01

Intergroup conflict is often driven by an individual's motivation to protect oneself and fellow group members against the threat of out-group aggression, including the tendency to pre-empt out-group threat through a competitive approach. Here we link such defense-motivated competition to oxytocin, a hypothalamic neuropeptide involved in reproduction and social bonding. An intergroup conflict game was developed to disentangle whether oxytocin motivates competitive approach to protect (i) immediate self-interest, (ii) vulnerable in-group members, or (iii) both. Males self-administered oxytocin or placebo (double-blind placebo-controlled) and made decisions with financial consequences to themselves, their fellow in-group members, and a competing out-group. Game payoffs were manipulated between-subjects so that non-cooperation by the out-group had high vs. low impact on personal payoff (personal vulnerability), and high vs. low impact on payoff to fellow in-group members (in-group vulnerability). When personal vulnerability was high, non-cooperation was unaffected by treatment and in-group vulnerability. When personal vulnerability was low, however, in-group vulnerability motivated non-cooperation but only when males received oxytocin. Oxytocin fuels a defense-motivated competitive approach to protect vulnerable group members, even when personal fate is not at stake.

Pilot study demonstrates that salivary oxytocin can be measured unobtrusively in preterm infants.

PubMed

Kommers, D R; Broeren, Mac; Andriessen, P; Oei, S G; Feijs, L; Bambang Oetomo, S

2017-01-01

This study assessed the feasibility and obtrusiveness of measuring salivary oxytocin in preterm infants receiving Kangaroo care, because this is a period of maximal bonding or co-regulation. We also analysed possible influential determinants, including maternal oxytocin. The saliva of preterm infants and their mothers was collected prior to, and during, Kangaroo care using cotton swabs and pooled into vials until sufficient volumes were obtained to measure oxytocin levels using a radioimmunoassay. The obtrusiveness of the infants' collections was measured with a Likert scale. Saliva was collected unobtrusively prior to, and during, 30 Kangaroo care sessions in 21 preterm infants. This resulted in three vials with sufficient volumes of before-Kangaroo care saliva and three with during-Kangaroo care saliva. Oxytocin was detectable in all six vials. The Kangaroo care duration and the intensity of the mother-infant interaction before and during Kangaroo care seemed to be the most important determinants, and these should preferably be standardised in any future trials. Oxytocin was measured unobtrusively in the pooled saliva of preterm infants both before and during Kangaroo care and could therefore be investigated as a biomarker in future studies. ©2016 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.

An association between belief in life after death and serum oxytocin in older people in rural Japan.

PubMed

Imamura, Yoshiomi; Mizoguchi, Yoshito; Nabeta, Hiromi; Haraguchi, Yoshinori; Matsushima, Jun; Kojima, Naoki; Kawashima, Toshiro; Yamada, Shigeto; Monji, Akira

2017-01-01

Previous research suggests that spirituality/religiosity has benefits for both mental and physical health, measured using biological indices such as cortisol and IL-6. However, there have been few studies concerning the association of religious beliefs with oxytocin, a neuropeptide hormone secreted by the pituitary. Levels of peripheral oxytocin are thought to reflect the strength of bonding and stress regulation in social relationships. As such, the oxytocin system may underpin the biological mechanisms by which belief in life after death is associated with good mental and physical health. Here, we examine associations between oxytocin and belief in life after death. We recruited 317 community-dwelling people, aged 65 or older, without cognitive or mental deficits, and living in rural Japan. We recorded demographics, belief in life after death, and logical memory using the Wechsler Memory Scale. Levels of serum oxytocin were obtained using an enzyme immunoassay method. Serum oxytocin levels were higher among women than men and were negatively associated with strength of belief in life after death. Our findings could be interpreted differently depending on whether the anxiogenic or anxiolytic function of the oxytocin system is considered. Greater endorsement of afterlife beliefs may reduce secure attachment. Alternatively, based on the literature suggesting that basal levels of oxytocin are lower in those with reduced relational distress or anxiety, afterlife beliefs may play a role in these reductions. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The Multidimensional Therapeutic Potential of Targeting the Brain Oxytocin System for the Treatment of Substance Use Disorders.

PubMed

Bowen, Michael T; Neumann, Inga D

2017-09-24

The neuropeptide oxytocin is released both into the blood and within the brain in response to reproductive stimuli, such as birth, suckling and sex, but also in response to social interaction and stressors. Substance use disorders, or addictions, are chronic, relapsing brain disorders and are one of the major causes of global burden of disease. Unfortunately, current treatment options for substance use disorders are extremely limited and a treatment breakthrough is sorely needed. There is mounting preclinical evidence that targeting the brain oxytocin system may provide that breakthrough. Substance use disorders are characterised by a viscous cycle of bingeing and intoxication, followed by withdrawal and negative affect, and finally preoccupation and anticipation that triggers relapse and further consumption. Administration of oxytocin has been shown to have a potential therapeutic benefit at each stage of this addiction cycle for numerous drugs of abuse. This multidimensional therapeutic utility is likely due to oxytocin's interactions with key biological systems that underlie the development and maintenance of addiction. Only a few human trials of oxytocin in addicted populations have been completed with the results thus far being mixed. There are numerous other trials underway, and the results are eagerly awaited. However, the ability to fully harness the potential therapeutic benefit of targeting the brain oxytocin system may depend on the development of molecules that selectively stimulate the oxytocin system, but that have superior pharmacokinetic properties to oxytocin itself.

Oxytocin and vasopressin neural networks: implications for social behavioral diversity and translational neuroscience

PubMed Central

Johnson, Zachary V.; Young, Larry J.

2017-01-01

Oxytocin- and vasopressin-related systems are present in invertebrate and vertebrate bilaterian animals, including humans, and exhibit conserved neuroanatomical and functional properties. In vertebrates, these systems innervate conserved neural networks that regulate social learning and behavior, including conspecific recognition, social attachment, and parental behavior. Individual and species-level variation in central organization of oxytocin and vasopressin systems has been linked to individual and species variation in social learning and behavior. In humans, genetic polymorphisms in the genes encoding oxytocin and vasopressin peptides and/or their respective target receptors have been associated with individual variation in social recognition, social attachment phenotypes, parental behavior, and psychiatric phenotypes such as autism. Here we describe both conserved and variable features of central oxytocin and vasopressin systems in the context of social behavioral diversity, with a particular focus on neural networks that modulate social learning, behavior, and salience of sociosensory stimuli during species-typical social contexts. PMID:28434591

A Direct Examination of the Effect of Intranasal Administration of Oxytocin on Approach-Avoidance Motor Responses to Emotional Stimuli

PubMed Central

Theodoridou, Angeliki; Penton-Voak, Ian S.; Rowe, Angela C.

2013-01-01

Oxytocin has been shown to promote a host of social behaviors in humans but the exact mechanisms by which it exerts its effects are unspecified. One prominent theory suggests that oxytocin increases approach and decreases avoidance to social stimuli. Another dominant theory posits that oxytocin increases the salience of social stimuli. Herein, we report a direct test of these hypotheses. In a double-blind, placebo-controlled study we examined approach-avoidance motor responses to social and non-social emotional stimuli. One hundred and twenty participants self-administered either 24 IU oxytocin or placebo and moved a lever toward or away from pictures of faces depicting emotional expressions or from natural scenes appearing before them on a computer screen. Lever movements toward stimuli decreased and movements away increased stimuli size producing the illusion that stimuli moved away from or approached participants. Reaction time data were recorded. The task produced the effects that were anticipated on the basis of the approach-avoidance literature in relation to emotional stimuli, yet the anticipated speeded approach and slowed avoidance responses to emotional faces by the oxytocin group were not observed. Interestingly, the oxytocin treatment group was faster to approach and avoid faces depicting disgust relative to the placebo group, suggesting a salience of disgust for the former group. Results also showed that within the oxytocin group women's reaction times to all emotional faces were faster than those of men, suggesting sex specific effects of oxytocin. The present findings provide the first direct evidence that intranasal oxytocin administration does not enhance approach/avoidance to social stimuli and does not exert a stronger effect on social vs. non-social stimuli in the context of processing of emotional expressions and scenes. Instead, our data suggest that oxytocin administration increases the salience of certain social stimuli and point to a

A direct examination of the effect of intranasal administration of oxytocin on approach-avoidance motor responses to emotional stimuli.

PubMed

Theodoridou, Angeliki; Penton-Voak, Ian S; Rowe, Angela C

2013-01-01

Oxytocin has been shown to promote a host of social behaviors in humans but the exact mechanisms by which it exerts its effects are unspecified. One prominent theory suggests that oxytocin increases approach and decreases avoidance to social stimuli. Another dominant theory posits that oxytocin increases the salience of social stimuli. Herein, we report a direct test of these hypotheses. In a double-blind, placebo-controlled study we examined approach-avoidance motor responses to social and non-social emotional stimuli. One hundred and twenty participants self-administered either 24 IU oxytocin or placebo and moved a lever toward or away from pictures of faces depicting emotional expressions or from natural scenes appearing before them on a computer screen. Lever movements toward stimuli decreased and movements away increased stimuli size producing the illusion that stimuli moved away from or approached participants. Reaction time data were recorded. The task produced the effects that were anticipated on the basis of the approach-avoidance literature in relation to emotional stimuli, yet the anticipated speeded approach and slowed avoidance responses to emotional faces by the oxytocin group were not observed. Interestingly, the oxytocin treatment group was faster to approach and avoid faces depicting disgust relative to the placebo group, suggesting a salience of disgust for the former group. Results also showed that within the oxytocin group women's reaction times to all emotional faces were faster than those of men, suggesting sex specific effects of oxytocin. The present findings provide the first direct evidence that intranasal oxytocin administration does not enhance approach/avoidance to social stimuli and does not exert a stronger effect on social vs. non-social stimuli in the context of processing of emotional expressions and scenes. Instead, our data suggest that oxytocin administration increases the salience of certain social stimuli and point to a

Association Between Maternal Mood and Oxytocin Response to Breastfeeding

PubMed Central

Grewen, Karen; Meltzer-Brody, Samantha

2013-01-01

Abstract Background Postpartum depression is associated with reduced breastfeeding duration. We previously hypothesized that shared neuroendocrine mechanisms underlie this association. We sought to measure the association between maternal mood and neuroendocrine response to breastfeeding. Methods We conducted a longitudinal cohort study of women recruited during pregnancy who intended to breastfeed. Baseline depression and anxiety history were assessed with a structured clinical interview. We measured mood symptoms using validated psychometric instruments, and we quantified affect and neuroendocrine responses to breastfeeding during laboratory visits at 2 and 8 weeks postpartum. Results We recruited 52 women who intended to breastfeed, among whom 47 completed 8-week follow-up. Duration and intensity of breastfeeding through 8 weeks were similar among mothers with lower versus higher anxiety and depression scores. In the third trimester, oxytocin was inversely correlated with Edinburgh Postnatal Depression Scale (EPDS) score (p=0.03). We did not find differences in neuroendocrine profile during breastfeeding at 2 weeks postpartum. Among the 39 women who breastfed at 8 weeks postpartum, oxytocin area under the curve during breastfeeding was inversely correlated with maternal EPDS and STAI-State and STAI-Trait anxiety scores (all p≤0.01). Higher anxiety and depression scores was further associated with lower oxytocin (group p<0.05) during feeding. During feeding at both visits, higher anxiety and depression scores were also associated with more negative affect: mothers reported feeling less happy and more depressed, overwhelmed, and stressed during feeding than women with lower scores. Conclusion Symptoms of depression and anxiety were associated with differences in oxytocin response and affect during breastfeeding. PMID:23586800

Mitigation of sociocommunicational deficits of autism through oxytocin-induced recovery of medial prefrontal activity: a randomized trial.

PubMed

Watanabe, Takamitsu; Abe, Osamu; Kuwabara, Hitoshi; Yahata, Noriaki; Takano, Yosuke; Iwashiro, Norichika; Natsubori, Tatsunobu; Aoki, Yuta; Takao, Hidemasa; Kawakubo, Yuki; Kamio, Yoko; Kato, Nobumasa; Miyashita, Yasushi; Kasai, Kiyoto; Yamasue, Hidenori

2014-02-01

Sociocommunicational deficits make it difficult for individuals with autism spectrum disorders (ASD) to understand communication content with conflicting verbal and nonverbal information. Despite growing prospects for oxytocin as a therapeutic agent for ASD, no direct neurobiological evidence exists for oxytocin's beneficial effects on this core symptom of ASD. This is slowing clinical application of the neuropeptide. To directly examine whether oxytocin has beneficial effects on the sociocommunicational deficits of ASD using both behavioral and neural measures. At the University of Tokyo Hospital, we conducted a randomized, double-blind, placebo-controlled, within-subject-crossover, single-site experimental trial in which intranasal oxytocin and placebo were administered. A total of 40 highly functioning men with ASD participated and were randomized in the trial. Single-dose intranasal administration of oxytocin (24 IU) and placebo. Using functional magnetic resonance imaging, we examined effects of oxytocin on behavioral neural responses of the participants to a social psychological task. In our previous case-control study using the same psychological task, when making decisions about social information with conflicting verbal and nonverbal contents, participants with ASD made judgments based on nonverbal contents less frequently with longer time and could not induce enough activation in the medial prefrontal cortex. Therefore, our main outcomes and measures were the frequency of the nonverbal information-based judgments (NVJs), the response time for NVJs, and brain activity of the medial prefrontal cortex during NVJs. Intranasal oxytocin enabled the participants to make NVJs more frequently (P = .03) with shorter response time (P = .02). During the mitigated behavior, oxytocin increased the originally diminished brain activity in the medial prefrontal cortex (P < .001). Moreover, oxytocin enhanced functional coordination in the area (P < .001), and the

Nanomolar Oxytocin Synergizes with Weak Electrical Afferent Stimulation to Activate the Locomotor CPG of the Rat Spinal Cord In Vitro

PubMed Central

Dose, Francesco; Zanon, Patrizia; Coslovich, Tamara; Taccola, Giuliano

2014-01-01

Synergizing the effect of afferent fibre stimulation with pharmacological interventions is a desirable goal to trigger spinal locomotor activity, especially after injury. Thus, to better understand the mechanisms to optimize this process, we studied the role of the neuropeptide oxytocin (previously shown to stimulate locomotor networks) on network and motoneuron properties using the isolated neonatal rat spinal cord. On motoneurons oxytocin (1 nM–1 μM) generated sporadic bursts with superimposed firing and dose-dependent depolarization. No desensitization was observed despite repeated applications. Tetrodotoxin completely blocked the effects of oxytocin, demonstrating the network origin of the responses. Recording motoneuron pool activity from lumbar ventral roots showed oxytocin mediated depolarization with synchronous bursts, and depression of reflex responses in a stimulus and peptide-concentration dependent fashion. Disinhibited bursting caused by strychnine and bicuculline was accelerated by oxytocin whose action was blocked by the oxytocin antagonist atosiban. Fictive locomotion appeared when subthreshold concentrations of NMDA plus 5HT were coapplied with oxytocin, an effect prevented after 24 h incubation with the inhibitor of 5HT synthesis, PCPA. When fictive locomotion was fully manifested, oxytocin did not change periodicity, although cycle amplitude became smaller. A novel protocol of electrical stimulation based on noisy waveforms and applied to one dorsal root evoked stereotypic fictive locomotion. Whenever the stimulus intensity was subthreshold, low doses of oxytocin triggered fictive locomotion although oxytocin per se did not affect primary afferent depolarization evoked by dorsal root pulses. Among the several functional targets for the action of oxytocin at lumbar spinal cord level, the present results highlight how small concentrations of this peptide could bring spinal networks to threshold for fictive locomotion in combination with other

Meta-analytic review of the effects of a single dose of intranasal oxytocin on threat processing in humans.

PubMed

Leppanen, Jenni; Ng, Kah Wee; Kim, Youl-Ri; Tchanturia, Kate; Treasure, Janet

2018-01-01

Heightened threat sensitivity is a transdiagnostic feature in several psychiatric disorders. The neuropeptide oxytocin has been shown to reduce fear related behaviours and facilitated fear extinction in animals. These findings have led to increasing interest to explore the effects of intranasal oxytocin on threat processing in humans. The review included 26 studies (N = 1173), nine of which included clinical populations (N = 234). The clinical groups included were people with borderline personality disorder (BPD), anorexia nervosa, bulimia nervosa, depression, anxiety, and alcohol dependence disorder. We examined the effects of a single dose of intranasal oxytocin on startle response, attentional responses, and behavioural responses to threat. A single dose of intranasal oxytocin significantly increased the physiological startle response to threat in healthy people with a small effect size. However, oxytocin did not have significant effects on attentional bias towards social or disorder-specific threat, fixation towards threatening stimuli among healthy or clinical populations, or on threat related behavioural approach or avoidance responses. No studies investigated the effects of oxytocin on the startle response to threat among clinical populations. Additionally, only one of the reviewed studies had sufficient power to detect at least a moderate effect of oxytocin according to our criterion. The synthesis of literature suggest that oxytocin may influence the salience of threatening stimuli among healthy individuals, increasing the startle response to threat. It would be of interest to investigate the effects of oxytocin on the startle response to threat among clinical populations. Copyright © 2017 Elsevier B.V. All rights reserved.

Urinary oxytocin positively correlates with performance in facial visual search in unmarried males, without specific reaction to infant face.

PubMed

Saito, Atsuko; Hamada, Hiroki; Kikusui, Takefumi; Mogi, Kazutaka; Nagasawa, Miho; Mitsui, Shohei; Higuchi, Takashi; Hasegawa, Toshikazu; Hiraki, Kazuo

2014-01-01

The neuropeptide oxytocin plays a central role in prosocial and parental behavior in non-human mammals as well as humans. It has been suggested that oxytocin may affect visual processing of infant faces and emotional reaction to infants. Healthy male volunteers (N = 13) were tested for their ability to detect infant or adult faces among adult or infant faces (facial visual search task). Urine samples were collected from all participants before the study to measure the concentration of oxytocin. Urinary oxytocin positively correlated with performance in the facial visual search task. However, task performance and its correlation with oxytocin concentration did not differ between infant faces and adult faces. Our data suggests that endogenous oxytocin is related to facial visual cognition, but does not promote infant-specific responses in unmarried men who are not fathers.

Effects of oxytocin on behavioral and ERP measures of recognition memory for own-race and other-race faces in women and men.

PubMed

Herzmann, Grit; Bird, Christopher W; Freeman, Megan; Curran, Tim

2013-10-01

Oxytocin has been shown to affect human social information processing including recognition memory for faces. Here we investigated the neural processes underlying the effect of oxytocin on memorizing own-race and other-race faces in men and women. In a placebo-controlled, double-blind, between-subject study, participants received either oxytocin or placebo before studying own-race and other-race faces. We recorded event-related potentials (ERPs) during both the study and recognition phase to investigate neural correlates of oxytocin's effect on memory encoding, memory retrieval, and perception. Oxytocin increased the accuracy of familiarity judgments in the recognition test. Neural correlates for this effect were found in ERPs related to memory encoding and retrieval but not perception. In contrast to its facilitating effects on familiarity, oxytocin impaired recollection judgments, but in men only. Oxytocin did not differentially affect own-race and other-race faces. This study shows that oxytocin influences memory, but not perceptual processes, in a face recognition task and is the first to reveal sex differences in the effect of oxytocin on face memory. Contrary to recent findings in oxytocin and moral decision making, oxytocin did not preferentially improve memory for own-race faces. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

PubMed

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.

Effects of oxytocin on behavioral and ERP measures of recognition memory for own-race and other-race faces in women and men

PubMed Central

Herzmann, Grit; Bird, Christopher W.; Freeman, Megan; Curran, Tim

2013-01-01

Oxytocin has been shown to affect human social information processing including recognition memory for faces. Here we investigated the neural processes underlying the effect of oxytocin on memorizing own-race and other-race faces in men and women. In a placebo-controlled, doubleblind, between-subject study, participants received either oxytocin or placebo before studying own-race and other-race faces. We recorded event-related potentials (ERPs) during both the study and recognition phase to investigate neural correlates of oxytocin’s effect on memory encoding, memory retrieval, and perception. Oxytocin increased the accuracy of familiarity judgments in the recognition test. Neural correlates for this effect were found in ERPs related to memory encoding and retrieval but not perception. In contrast to its facilitating effects on familiarity, oxytocin impaired recollection judgments, but in men only. Oxytocin did not differentially affect own-race and other-race faces. This study shows that oxytocin influences memory, but not perceptual processes, in a face recognition task and is the first to reveal sex differences in the effect of oxytocin on face memory. Contrary to recent findings in oxytocin and moral decision making, oxytocin did not preferentially improve memory for own-race faces. PMID:23648370

Intranasal Oxytocin Affects Amygdala Functional Connectivity after Trauma Script-Driven Imagery in Distressed Recently Trauma-Exposed Individuals.

PubMed

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

2016-04-01

Approximately 10% of trauma-exposed individuals go on to develop post-traumatic stress disorder (PTSD). Neural emotion regulation may be etiologically involved in PTSD development. Oxytocin administration early post-trauma may be a promising avenue for PTSD prevention, as intranasal oxytocin has previously been found to affect emotion regulation networks in healthy individuals and psychiatric patients. In a randomized double-blind placebo-controlled between-subjects functional magnetic resonance (fMRI) study, we assessed the effects of a single intranasal oxytocin administration (40 IU) on seed-based amygdala resting-state FC with emotion regulation areas (ventromedial prefrontal cortex (vmPFC), ventrolateral prefrontal cortex (vlPFC)), and salience processing areas (insula, dorsal anterior cingulate cortex (dACC)) in 37 individuals within 11 days post trauma. Two resting-state scans were acquired; one after neutral- and one after trauma-script-driven imagery. We found that oxytocin administration reduced amygdala-left vlPFC FC after trauma script-driven imagery, compared with neutral script-driven imagery, whereas in PL-treated participants enhanced amygdala-left vlPFC FC was observed following trauma script-driven imagery. Irrespective of script condition, oxytocin increased amygdala-insula FC and decreased amygdala-vmPFC FC. These neural effects were accompanied by lower levels of sleepiness and higher flashback intensity in the oxytocin group after the trauma script. Together, our findings show that oxytocin administration may impede emotion regulation network functioning in response to trauma reminders in recently trauma-exposed individuals. Therefore, caution may be warranted in administering oxytocin to prevent PTSD in distressed, recently trauma-exposed individuals.