Exogenous Oxytocin Administration Research Articles

Effect of chronic exogenous oxytocin administration on exercise performance and cardiovagal control in hypobaric hypoxia in rats

BackgroundOutstanding exercise performance has been associated with an exacerbated vagal outflow. Nevertheless, during high-altitude hypobaric-hypoxia (HH), there is a baroreflex-dependent parasympathetic withdrawal and exercise performance deterioration. Notably, vagal control is pivotal in exercise performance, and exogenous oxytocin (OXY) administration has been shown to enhance parasympathetic drive; however, no evidence shows their role in exercise performance during HH. Then, this study aimed to examine the effect of prolonged exogenous oxytocin (OXY) administration on exercise performance during hypobaric hypoxia (HH) in rats.ResultsA vehicle group (n = 6) and an OXY group (n = 6) performed incremental exercise and baroreflex tests during both normobaric normoxia (NN) and HH (PO2: 100 mmHg, simulated 3,500 m) prior (pre-) and after (post-) 14 days of administration. The results showed that at pre-, there were no significant differences in exercise performance between the two groups, while at post-, the OXY group exhibited similar performance between NN and HH, while the Vehicle group maintained a significant decline in performance at HH compared to NN. At post-, the Vehicle group also demonstrated a reset in the baroreflex and a worse bradycardic response in HH, which was reversed in the OXY group, while the hypoxic ventilatory response was similar in both groups.ConclusionThe findings suggest prolonged OXY administration prevents impaired exercise performance and vagal control during short-term HH.

Association between Flexibility, Measured with the Back-Scratch Test, and the Odds of Oxytocin Administration during Labour and Caesarean Section.

Objective: This study explored whether assessing flexibility levels in clinical settings might predict the odds of oxytocin administration and caesarean section to stimulate labour. Methods: Pregnant women from the GESTAFIT Project (n = 157), participated in this longitudinal study. Maternal upper-body flexibility was assessed at 16 gestational weeks (g.w.) through the Back-scratch test. Clinical data, including oxytocin administration and type of birth, were registered from obstetric medical records. Results: Pregnant women who required oxytocin administration or had caesarean sections showed lower flexibility scores (p < 0.05 and p < 0.01, respectively). The receiver operating characteristic curve analysis showed that the Back-scratch test was able to detect the need for oxytocin administration ((area under the curve [AUC] = 0.672 (95% confidence interval [CI]: 0.682 (95% CI: 0.59-0.78, p = 0.001)). The AUC to establish the ability of flexibility to discriminate between vaginal and caesarean section births was 0.672 (95% CI: 0.60-0.77, p = 0.002). A Back-scratch test worse than 4 centimetres was associated with a ~5 times greater increased odds ratio of requiring exogenous oxytocin administration (95% CI: 2.0-11.6, p = 0.001) and a ~4 times greater increased odds ratio of having a caesarean section (95% CI: 1.7-10.2, p = 0.002). Conclusions: These findings suggest that lower flexibility levels at the 16th g.w. discriminates between pregnant women who will require oxytocin and those who will not, and those with a greater risk of a caesarean section than those with a vaginal birth. Pregnant women below the proposed Back-scratch test cut-offs at 16th g.w. might specifically benefit from physical therapies that include flexibility training.

Exogenous oxytocin administered to induce or augment labour is positively associated with quality of observed mother-infant bonding

Oxytocin is a key hormone in the transition to motherhood. The maternal endogenous oxytocin system facilitates many physiological and biological adaptations, including breastfeeding, maternal wellbeing, and brain plasticity. Additionally, maternal endogenous oxytocin works as a finetuned orchestrator prior to, during, and after the birth of a child to support birth progression and mother-infant bonding. Exogenous oxytocin may be administered to induce or augment labour when this is not progressing naturally and is a common obstetric intervention worldwide. However, the lasting impact of these widely varying levels of systemic exogenous oxytocin on mother-infant bonding is currently unknown. This study aimed to investigate the association between exogenous oxytocin administered to induce or augment labour and quality of observed mother-infant bonding.Thirty-eight mother and infant dyads participated (mothers aged 24–48 years; infants aged 2–5 months). Mother-infant bonding quality was assessed via the Recorded Interaction Task and hospital birth records were consulted to obtain exogenous oxytocin administration data. Demographic information and possible confounding factors were collected from dyads, and salivary oxytocin concentration was measured for both mother and infant.Mother's perception of infant sleep difficulty was identified as a confounding factor for quality of mother-infant bonding. After controlling for the confounding factor, receiving exogenous oxytocin to induce or augment labour, as opposed to not, was found to be significantly positively associated with higher quality of observed mother-infant bonding (p = 0.029). These novel findings highlight the need for further exploration, both of the impact of the treatment and of the mechanisms of action of intrapartum exogenous oxytocin on the endogenous oxytocin system. It is argued that particular focus be given to investigate action on the central oxytocin receptors, and if this may play a role in subsequent mother-infant bonding outcomes. It is vital to understand the full breadth and the clinical implications of this commonplace procedure.

Social functioning predicts individual changes in EEG microstates following intranasal oxytocin administration: Adouble-blind, cross-over randomized clinical trial.

Oxytocin (OXT) modulates social behaviors. However, the administration of exogenous OXT in humans produces inconsistent behavioral changes, affecting future consideration of OXT as a treatment for autism and other disorders with social symptoms. Inter-individual variability in social functioning traits might play a key role in how OXT changes brain activity and, therefore, behavior. Here, we investigated if inter-individual variability might dictate how single-dose intranasal OXT administration (IN-OXT) changes spontaneous neural activity during the eyes-open resting state. We used a double-blinded, randomized, placebo-controlled, cross-over design on 30 typically developing young adult men to investigate the dynamics of EEG microstates corresponding to activity in defined neural networks. We confirmed previous reports that, at the group level, IN-OXT increases the representation of the attention and salience microstates. Furthermore, we identified a decreased representation of microstates associated with the default mode network. Using multivariate partial least square statistical analysis, we found that social functioning traits associated with IN-OXT-induced changes in microstate dynamics in specific spectral bands. Correlation analysis further revealed that the higher the social functioning, the more IN-OXT increased the appearance of the visual network-associated microstate, and suppressed the appearance of a default mode network-related microstate. The lower the social functioning, the more IN-OXT increases the appearance of the salience microstate. The effects we report on the salience microstate support the hypothesis that OXT regulates behavior by enhancing social salience. Moreover, our findings indicate that social functioning traits modulate responses to IN-OXT and could partially explain the inconsistent reports on IN-OXT effects.

Exogenous Oxytocin Administration Restores Memory in Female APP/PS1 Mice.

Current treatment options for Alzheimer's disease (AD) are limited, inefficient, and often have serious side effects. Oxytocin is a neuropeptide implicated in a variety of central processes, such as social and reproductive behaviors. Among others, it has garnered attention in various domains of psychiatric research, while its role in the development and course of neurodegenerative disorders like AD is rather unknown. This study aimed to investigate the role of exogenous oxytocin administration on memory, specifically in view of AD, as a potential novel treatment option. We describe a novel treatment approach by using a relatively low dose of long-term intranasal oxytocin treatment, to restore memory deficits in female APPswePS1dE9 mice. Female APPswePS1dE9 mice treated with oxytocin showed increased spatial memory performance in the object location task and improved working memory in the Y-Maze, while indicating decreased sociability. These results indicate that oxytocin is able to reverse acquired cognitive deficits in female APPswePS1dE9 mice.

Transcriptional diversity of the oxytocin receptor in prairie voles: mechanistic implications for behavioral neuroscience and maternal physiology.

The neurohormone oxytocin regulates many aspects of physiology primarily by binding to its receptor, the oxytocin receptor. The oxytocin receptor gene (Oxtr) has been shown to have alternative transcripts in the mouse brain which may each have different biological functions or be used in specific contexts. A popular animal model for studying oxytocin-dependent social behaviors is the prairie vole, a biparental and monogamous rodent. Alternative transcriptional capacity of Oxtr in prairie voles is unknown. We used 5' rapid amplification of cDNA ends to identify alternative Oxtr transcription start sites in prairie vole brain tissue and uterine tissue. We then validated expression of specific transcripts in fetal brains and assessed the impact of exogenous oxytocin administration in utero on offspring brain development. We identified seven distinct Oxtr transcripts, all of which are present in both brain and uterine tissue. We then demonstrated that maternal oxytocin administration alters expression of a specific subset of Oxtr transcripts and that these different transcripts are under unique epigenetic regulation, such that in the perinatal period only one of the alternative transcripts is associated with DNA methylation in the Oxtr promoter. These data establish the existence of multiple Oxtr transcripts in prairie vole brain and uterine tissue and implicate oxytocin in the regulation of alternative transcript expression. These data have significant implications for our understanding of null mutant models in both mice and voles and translation in human birth and behavior.

Exploring the role of ex vivo metabolism on blood and plasma measurements of oxytocin among women in the third stage of labour: A post hoc study.

To examine the role of ex vivo oxytocin metabolism in post-dose peptide measurements. The stability of oxytocin (Study 1) and oxytocinase activity (Study 2) in late-stage pregnancy blood was quantified using liquid-chromatography tandem mass-spectrometry (LC-MS/MS) and a fluorogenic assay, respectively. Analyses were conducted using blood from pregnant women (>36 weeks gestation) evaluated in lithium heparin (LH), ethylenediaminetetraacetic acid (EDTA) and BD P100 blood collection tubes with or without protease inhibitors. In addition, plasma oxytocin concentrations following administration of oxytocin 240 IU inhaled, 5IU intravenous or 10IU intramuscular in women in third stage of labour (TSL) were analysed using enzyme-linked immunosorbent assay (ELISA) and LC-MS/MS to understand how quantified peptide concentrations differ between these analytical methods (Study 3). Study 1: Oxytocin was stable in blood collected into EDTA tubes with or without protease inhibitors but not in LH tubes. Study 2: Blood collected into all EDTA-containing collection tubes led to near-complete inhibition of oxytocinase (≤100 min). In plasma, a 35% reduction in oxytocinase activity was observed in LH tubes with EDTA added. In plasma from late-stage pregnancy compared to nonpregnant participants, the oxytocinase activity was approximately 11-fold higher. Study 3: Plasma oxytocin concentrations from nonpregnant or women in TSL following exogenous oxytocin administration were ≤33 times higher when analysed using ELISA vs. LC-MS/MS methods. Collection of blood from late-stage pregnant women into tubes containing EDTA inhibits oxytocinase effectively stabilizing oxytocin, suggesting low concentrations of oxytocin after dose administration reflect rapid in vivo metabolism.

A study of the pharmacokinetics and pharmacodynamics of oxytocin at elective caesarean delivery.

Oxytocin is widely used to prevent atonic postpartum haemorrhage after caesarean delivery. Initial treatment failure rates are high and inadequate dosing may contribute. Excessive doses, however, are associated with serious adverse effects. The pharmacokinetic data from this context are sparse and there is a lack of data in the immediate postpartum minutes after an initiating bolus. The pharmacodynamic data from this context are exclusively from dose-effect studies, with some suggesting that higher doses of oxytocin are required to provide adequate uterine tone in obese compared with non-obese women. We aimed to perform a pharmacokinetic and pharmacodynamic study that would facilitate more precise weight-based oxytocin dosing. We measured arterial oxytocin concentration, uterine tone and haemodynamic parameters in 25 women in the first 40 min after exogenous oxytocin administration at elective caesarean delivery. Serum oxytocin concentrations varied considerably between individuals. We constructed a one-compartment pharmacokinetic model of exogenous oxytocin deposition, after its administration with an initiating bolus and a maintenance infusion, at elective caesarean delivery. Body weight was evaluated as a potential covariate but was not included in the model due to lack of statistically significant reduction in the objective function. We calculated the volume of distribution and clearance (mean [coefficient of variation]) as 156.1 l [18%] and 83 ml.s-1 [32%] but found no within-individual correlation between serum oxytocin concentration and uterine tone or haemodynamic parameters. In conclusion, we observed a large variation in serum oxytocin concentrations between individuals receiving similar doses of oxytocin and were unable to establish weight-based dosing of exogenous oxytocin at caesarean delivery. Our findings suggest that future studies on oxytocin pharmacokinetics would need large sample sizes. In the absence of such data, oxytocin dosing should continue to be guided by uterine tone assessments and adjusted according to a strategy based on the best evidence from dose-effect studies.

Exogenous oxytocin administration during labor and autism spectrum disorder

Oxytocin is a neuropeptide hormone that plays a key role in social behaviour, stress regulation, and mental health. Synthetic oxytocin administration is a common obstetrical practice, and importantly, previous research has suggested that intrapartum exposure may increase the risk of neurodevelopmental disorders, such as autism spectrum disorder (ASD). To examine the association between synthetic oxytocin exposure during labor and ASD diagnosis in the child. This population-based retrospective cohort study compared two cohorts of children: 1) all children born in British Columbia (BC), Canada between April 1, 2000 and December 31, 2014 (n = 414,336 births), and 2) all children delivered at Soroka University Medical Center (SUMC) in Be'er Sheva, Israel between January 1, 2011 and December 31, 2019 (n = 82,892 births). Nine different exposure groups were examined. Cox proportional hazards models were used to estimate crude and adjusted hazard ratios of ASD in both cohorts based on induction and/or augmentation exposures status. To further control for confounding by indication, we conducted sensitivity analyses among a cohort of healthy, uncomplicated deliveries and among a group that was induced only for post-dates. Additionally, we stratified our analyses by infant sex to assess for potential sex differences. In the BC cohort, 170,013 of 414,336 deliveries (41.0%) were not induced or augmented, 107,543 (26.0%) were exposed to oxytocin, and 136,780 (33.0%) were induced or augmented but not exposed to oxytocin. In the Israel cohort, 51,790 of 82,892 deliveries (62.5%) were not induced or augmented, 28,852 (34.8%) were exposed to oxytocin, and 2,250 (2.7%) were induced or augmented but not exposed to oxytocin. Upon adjusting for covariates in the main analysis, significant associations were observed in the Israel cohort, including adjusted hazard ratios (aHRs) of 1.51 (95% CI 1.20, 1.90) for oxytocin augmented births and 2.18 (95% CI 1.32, 3.57) for those induced by means other than oxytocin and not augmented. However, oxytocin induction was not significantly associated with ASD in the Israel cohort. In the Canadian cohort, there were no statistically significant aHRs. Further, no significant sex differences were observed in the fully adjusted models. This study provides support that induction of labor through oxytocin administration does not increase the risk of ASD in the child. Our international comparison of two countries with differences in clinical practice regarding oxytocin administration for induction and/or augmentation suggests that previous studies reporting a significant association were likely confounded by the underlying indication for the induction.

Sniffing oxytocin: Nose to brain or nose to blood?

In recent years ample studies have reported that intranasal administration of the neuropeptide oxytocin can facilitate social motivation and cognition in healthy and clinical populations. However, it is still unclear how effects are mediated since intranasally administered oxytocin can both directly enter the brain (nose to brain) and increase peripheral vascular concentrations (nose to blood). The relative functional contributions of these routes are not established and have received insufficient attention in the field. The current study used vasoconstrictor pretreatment to prevent intranasal oxytocin (24 IU) from increasing peripheral concentrations and measured effects on both resting-state neural (electroencephalography) and physiological responses (electrocardiogram, electrogastrogram and skin conductance). Results demonstrated that intranasal oxytocin alone produced robust and widespread increases of delta-beta cross-frequency coupling (CFC) from 30 min post-treatment but did not influence peripheral physiological measures. As predicted, vasoconstrictor pretreatment greatly reduced the normal increase in peripheral oxytocin concentrations and, importantly, abolished the majority of intranasal oxytocin effects on delta-beta CFC. Furthermore, time-dependent positive correlations were found between increases in plasma oxytocin concentrations and corresponding increases in delta-beta CFC following oxytocin treatment alone. Our findings suggest a critical role of peripheral vasculature-mediated routes on neural effects of exogenous oxytocin administration with important translational implications for its use as an intervention in psychiatric disorders.

Autonomic nervous system balance in parturient mares: Spontaneous vs induced delivery.

Delivery is not easily predictable in horses and the consequences of dystocia can be serious for both the mare and foal. An induction protocol with low doses of oxytocin has been reported as a safe procedure. This study investigates the effect of induced delivery on at-term mares' sympathetic-vagal balance. Fourteen mares were included and divided into two groups, one subjected to spontaneous delivery (SD), and one to induced delivery (ID). In both groups, an ECG was recorded using an elastic belt with integrated smart textile electrodes. The recording started before the delivery (Basal), continued close to delivery (Pre-delivery) and during delivery (Delivery), and ended after parturition (Placental expulsion). From the ECGs, Heart Rate Variability (HRV) parameters relating to time and frequency domains and non-linear analysis were extrapolated. The HRV analysis was performed both within the same group (IntraGA) and between the two groups (InterGA). In the present study, spontaneous and induced delivery did not appear to differ in autonomic nervous system functioning. In IntraGA analysis, both for SD and ID mares, delivery and placental expulsion periods were parasympathetic dominated since vagal-related HRV parameters increased. Moreover, no differences were found in InterGA comparison between SD and ID mares, except for the pre-delivery period of ID mares, during which both branches of the autonomic nervous system were activated. These results are in line with the literature on parasympathetic dominance during parturition and no change in Heart Rate Variability following exogenous oxytocin administration in parturient mares.

Clinical Experiences and Mechanism of Action with the Use of Oxytocin Injection at Parturition in Domestic Animals: Effect on the Myometrium and Fetuses.

Oxytocin is a key hormone for parturition and maternal traits in animals. During the peripartum period, the levels of endogenous oxytocin dictate physiological events such as myometrial contractions, prostaglandin production with the subsequent increase in oxytocin receptors, and the promotion of lactation when administered immediately after birth. While this hormone has some benefits regarding these aspects, the exogenous administration of oxytocin has been shown to have detrimental effects on the fetus, such as asphyxia, meconium staining, ruptured umbilical cords, and more dystocia cases in females. This review aims to analyze the main effects of oxytocin on myometrial activity during parturition, and its potential favorable and negative administration effects reflected in the fetus health of domestic animals. In conclusion, it is convenient to know oxytocin's different effects as well as the adequate doses and the proper moment to administrate it, as it can reduce labor duration, but it can also increase dystocia.

Alterations in the histology of the prostate of Sprague-Dawley rats treated with oxytocin

Background: The role of oxytocin in female reproductive system has been well studied. Very little is known about the long-term administration of oxytocin in prostatic tissues. This study aimed to assess the histological effects of prolonged administration of exogenous oxytocin on prostate in the male Sprague-Dawley rats.&#x0D; Methods: Twenty adult male Sprague-Dawley rats weighing between 180-250g were randomly distributed into four groups A, B, C and D of five rats each. Group A served as the control while groups B to D were the treated groups. Oxytocin was administered intramuscularly two days per week at the doses of 1, 2 and 3 IU/kg/b.w. to groups B, C and D respectively while 0.5ml of physiologic saline was administered to the control. The treatment was carried out over a period of 8 weeks (one spermatogenic cycle). At the end of study, blood was collected for testosterone assay and the prostate was also harvested for histological procedure.&#x0D; Result: Result showed significant decrease in the prostatic weight of all the treated groups. However, testosterone significantly increased in group D and the histology revealed moderate to severe stroma fibrosis, high vascularization with vascular congestion which was due to severe infiltration of inflammatory cells in a dose dependent manner.&#x0D; Conclusion: Prolonged administration of exogenous oxytocin could led to a decrease in prostatic weight. Hence, clinician prescribing oxytocin for the treatment of oligozoospermia should be conscious of the risk of exogenous oxytocin in inducing prostatic disorders.

Changes in Endogenous Oxytocin Levels and the Effects of Exogenous Oxytocin Administration on Body Weight Changes and Food Intake in Polycystic Ovary Syndrome Model Rats.

Polycystic ovary syndrome (PCOS) is frequently seen in females of reproductive age and is associated with metabolic disorders that are exacerbated by obesity. Although body weight reduction programs via diet and lifestyle changes are recommended for modifying reproductive and metabolic phenotypes, the drop-out rate is high. Thus, an efficacious, safe, and continuable treatment method is needed. Recent studies have shown that oxytocin (OT) reduces body weight gain and food intake, and promotes lipolysis in some mammals, including humans (especially obese individuals), without any adverse effects. In the present study, we evaluated the changes in endogenous OT levels, and the effects of acute and chronic OT administration on body weight changes, food intake, and fat mass using novel dihydrotestosterone-induced PCOS model rats. We found that the serum OT level was lower in PCOS model rats than in control rats, whereas the hypothalamic OT mRNA expression level did not differ between them. Acute intraperitoneal administration of OT during the dark phase reduced the body weight gain and food intake in PCOS model rats, but these effects were not observed in control rats. In contrast, chronic administration of OT decreased the food intake in both the PCOS model rats and control rats. These findings indicate that OT may be a candidate medicine that is efficacious, safe, and continuable for treating obese PCOS patients.

Barriers and Breakthroughs in Targeting the Oxytocin System to Treat Alcohol Use Disorder.

Development of better treatments for alcohol use disorder (AUD) is urgently needed. One promising opportunity for this development is the potential of targeting the oxytocin peptide system. Preclinical studies showed that administration of exogenous oxytocin or, more recently, stimulation of neurons expressing endogenous oxytocin lead to a decreased alcohol consumption across several rodent models. Initial clinical studies also showed that administration of oxytocin decreased craving for alcohol and heavy alcohol drinking. However, several more recent clinical studies were not able to replicate these effects. Thus, although targeting the oxytocin system holds promise for the treatment of AUD, more nuanced approaches toward development and application of these treatments are needed. In this mini-review we discuss potential caveats resulting in differential success of attempts to use oxytocin for modulating alcohol use disorder-related behaviors in clinical studies and evaluate three directions in which targeting the oxytocin system could be improved: (1) increasing potency of exogenously administered oxytocin, (2) developing oxytocin receptor agonists, and (3) stimulating components of the endogenous oxytocin system. Both advances and potential pitfalls of these directions are discussed.

Effect of exogenous administration of oxytocin on postpartum follicular dynamics, oestrous rate and ovulation in Nili-Ravi buffaloes.

Based on different surveys, dairy farmers are concerned about extensive use of exogenous oxytocin in buffaloes, which is being held responsible for reproductive problems including irregular oestrous cycle and delayed ovulation. For these concerns, effects of oxytocin injection on postpartum follicular dynamics, postpartum oestrous interval (PEI), oestrous length, the interval from onset of estrus to ovulation and blood progesterone (P4) were studied in Nili-Ravi buffaloes. For this purpose, 23 animals within 1week after calving were randomly divided into three groups: without oxytocin (CON; n=7), 10 i.u. oxytocin (LOW; n=8), 30 i.u. oxytocin - (HIGH; n=8) and used to record the PEI for the study period of 154days. At subsequent estrus, three buffaloes from each group (not served) were selected randomly to monitor two cycles for 6weeks. Transrectal ultrasonography was performed to evaluate follicular and corpus luteum (CL) development, and blood sampling was done for progesterone (P4) analysis. These results revealed that postpartum oestrous interval (PEI) decreased significantly in oxytocin-treated groups. The number of small, medium and total follicles on the left ovary was significantly higher in the HIGH group. However, an overall number of small and total follicles on both right and left ovaries was significantly higher in CON and HIGH groups. On the other hand, there was no difference in the number of follicles on the right ovary among all treatment groups. The same was true for the size of pre-ovulatory follicles, CL, P4 concentrations and oestrous cycle length. The intervals from onset of estrus to ovulation and from standing estrus to ovulation were increased considerably in the HIGH group. It is concluded that exogenous oxytocin administration resulted in the shortening of PEI but triggered a delay in ovulation. Moreover, a higher dose of oxytocin could stimulate the growth of small, medium, and total follicles in postpartum Nili-Ravi buffaloes.

Activation of hypothalamic oxytocin neurons reduces binge-like alcohol drinking through signaling at central oxytocin receptors.

Preclinical and clinical evidence suggests that exogenous administration of oxytocin (OT) may hold promise as a therapeutic strategy for reducing heavy alcohol drinking. However, it remains unknown whether these effects are mediated by stimulation of endogenous sources of OT and signaling at oxytocin receptors (OTR) in brain or in the periphery. To address this question, we employed a targeted chemogenetic approach to examine whether selective activation of OT-containing neurons in the paraventricular nucleus of the hypothalamus (PVN) alters alcohol consumption in a binge-like drinking ("Drinking-in-the-Dark"; DID) model. Adult male Oxt-IRES-Cre mice received bilateral infusion of a Cre-dependent virus containing an excitatory DREADD (AAV8-hSyn-DIO-hM3Dq-mCherry) or control virus (AAV8-hSyn-DIO-mCherry) into the PVN. Chemogenetic activation of PVNOT+ neurons following clozapine-N-oxide injection reduced binge-like alcohol drinking in a similar manner as systemic administration of the neuropeptide. Pretreatment with a brain-penetrant OTR antagonist (L-368,899) reversed this effect while systemic administration of a peripherally restricted OTR antagonist (Atosiban) did not alter reduced alcohol drinking following chemogenetic activation of PVNOT+ neurons. Altogether, these data are the first to demonstrate that targeted activation of hypothalamic (endogenous) OT reduces alcohol consumption, providing further evidence that this neuropeptide plays a role in regulation of alcohol self-administration behavior. Further, results indicate that the ability OT to reduce alcohol drinking is mediated by signaling at OTR in the brain.

The link between oxytocin plasma levels and observed communication behaviors during sexual and nonsexual couple discussions: An exploratory study

The role of oxytocin (OT) in close relationships is complex, as both positive and negative associations have been found between OT and relationship processes. Also, with most research focusing on the effects of exogenous OT administration on communication and couple behaviors, our knowledge about the association between endogenous OT and couple dynamics remains limited. This study is the first to assess the link between peripheral OT levels and observed communication behaviors during sexual and nonsexual conflict discussions in romantic relationships. A sample of 126 young, heterosexual couples (Mean age = 23.3, SD = 2.4; average relationship duration = 1.9 years, SD = 0.9) participated in videotaped sexual and nonsexual couple conflict discussions of 7 min each. Communication behaviors were coded using an adaptation of the Specific Affect Coding System (SPAFF) and the System for Coding Interactions and Family Functioning (SCIFF). Blood samples were collected prior to the couple discussions, during a separate lab visit, and OT plasma levels were determined using enzyme-linked immunosorbent assays (ELISA). Plasma OT levels were positively associated with validating behaviors during sexual discussions in both women (r = +.24, p = .008) and men (r = +.18, p = .052). No significant associations were found between OT levels and validating behaviors during nonsexual discussions and between OT and affectionate and negative behaviors during either sexual or nonsexual discussions. Analyses revealed significant associations between OT levels and one’s own validating behaviors during sexual discussions (b = 47.82, t(201.16) = 3.81, p < .001) and one’s partner’s (b = 32.12, t(216.35) = 2.62, p = .009). The results highlight the biobehavioral aspects of couples’ sexual communication and may contribute to a better understanding of the processes involved in individual and relational well-being. This study is the first to report an association between peripheral OT levels and validating behaviors during sexual communication, indicating neurophysiological involvement in dyadic sexual communication patterns.

Delivering Clinically on Our Knowledge of Oxytocin and Sensory Stimulation: The Potential of Infant Carrying in Primary Prevention.

Oxytocin (OT) is one of the most intensively researched neuropeptides during the three past decades. In benign social contexts, OT exerts a range of desirable socioemotional, stress-reducing, and immunoregulatory effects in mammals and humans and influences mammalian parenting. Consequentially, research in potential pharmacological applications of OT toward human social deficits/disorders and physical illness has increased substantially. Regrettably, the results from the administration of exogenous OT are still relatively inconclusive. Research in rodent maternal developmental programming has demonstrated the susceptibility of offspring endogenous OT systems to maternal somatosensory stimulation, with consequences for behavioral, epigenetic, cognitive, and neurological outcomes. A translation of this animal research into practically feasible human parenting recommendations has yet to happen, despite the significant prevention potential implied by the maternal developmental programming research. Extended physical contact with full-term healthy infants in the months following birth (infant carrying) might constitute the human equivalent of those specific rodent maternal behaviors, found to positively influence emerging OT systems. Findings from both OT and maternal programming research parallel those found for infants exposed to such extended parental physical contact, whether through skin-to-skin contact or infant carrying. Clinical support of parents to engage in extended physical contact represents a feasible intervention to create optimum conditions for the development of infant OT systems, with potential beneficial long-term health effects.

Chapter 6 - Oxytocin, eating behavior, and metabolism in humans

The hypothalamic peptide oxytocin has been increasingly recognized as a hormone and neurotransmitter with important effects on energy intake, metabolism, and body weight and is under investigation as a potential novel therapeutic agent for obesity. The main neurons producing oxytocin and expressing the oxytocin receptor are strategically located in brain areas known to be critically involved in homeostatic energy balance as well as hedonic and motivational aspects of eating behavior. In this chapter, we will review the central and peripheral physiology of oxytocin and the interaction of oxytocin with key hormones and neural circuitries that affect food intake and metabolism. Next, we will synthesize the available data on endogenous oxytocin levels related to caloric intake, body weight, and metabolic status. We will then review the effects of exogenous oxytocin administration on eating behavior, body weight, and metabolism in humans, including in healthy individuals as well as specific populations with suspected perturbations involving oxytocin pathways. Finally, we will address the promise and fundamental challenges of translating this line of research to clinical care.