Oxytocin Administration Research Articles

STIMULATION OF CORTISOL SECRETION BY OXYTOCIN IN CLARIAS BATRACHUS (LINN.)

The present work reports the modulatory role of oxytocin on cortisol secretion by the interrenal cells in Clarias batrachus. Administration of dexamethasone @ 2.5 mg kg-1 body weight and captopril @8.3 mg kg-1 body weight for seven consecutive days resulted in a sharp fall in the cortisol level from 23.82 ± 1.248 µg dl-1 to 8.9 ± 3.47 µg dl-1. Treatment with oxytocin along with the above modulators resulted in an increase in cortisol level from 8.9 ± 3.47 µg dl to 12.84 ± 0.311 µg dl. Administration of oxytocin only, in the intact fish showed a stimulatory effect on the cortical production resulting in an increase from 23.82 ± 1.248 µg dl-1 to 31.9 ± 1.173 dl-1. The data were subjected to paired sample t-test and found to be significant at 95% confidence level. The present investigation clearly indicates a stimulatory effect of oxytocin in the regulation of cortisol secretion. Key words: Cortisol, oxytocin, Clarias batrachus

Effects of oxytocin administration on salivary sex hormone levels in autistic and neurotypical women

Effects of oxytocin administration on salivary sex hormone levels in autistic and neurotypical women

Autonomic Responses during Labor: Potential Implications for Takotsubo Syndrome

Takotsubo syndrome is a serious complication of labor. Although the pathophysiologic role of excessive sympathetic activation is established in this process, concurrent vagal responses have not been adequately described. Moreover, it remains unclear whether autonomic activity depends on the mode of delivery. Here, we explored the hypothesis that the different management of cesarean and vaginal delivery may elicit diverse responses affecting both autonomic arms. For this aim, continuous electrocardiographic recording was performed in 20 women during labor, and non-invasive indices of sympathetic and vagal activity were compared between the two modes of delivery. We report sympathetic prevalence during cesarean delivery, caused by marked vagal withdrawal, whereas autonomic activity was rather stable during vaginal delivery. These differences may be attributed to the effects of anesthesia during cesarean delivery, along with the protective effects of oxytocin administration during vaginal delivery. Our results provide further insights on autonomic responses during labor that may prove useful in the prevention of complications, such as takotsubo syndrome.

Congenital Hypothyroidism Can Dictate the Mode of Delivery and Intra-Labor Medication Usage

Background: Pregnancy and parturition reflect the complex interaction between physiological conditions of the mother and her offspring, and fetal health characteristics may affect maternal health throughout pregnancy and delivery. We aimed to investigate the characteristics of the mother-infant dyad of term infants detected as having congenital hypothyroidism (CH). Methods: A retrospective cohort study of 108,717 term infants delivered liveborn at Lis Maternity and Women's Hospital between 2010 and 2017. Infants were detected by the National Newborn Screening Program as having CH (131, 0.12%). Three years of surveillance in the Pediatric Endocrine Clinic revealed that 65 infants had transient CH and 66 had permanent CH. Data on maternal, pregnancy, delivery, and perinatal characteristics of the mother-infant dyads were retrieved from the hospital's electronic database. Results: Mode of delivery differed: a higher proportion of deliveries of CH infants required vacuum assistance, and more infants with CH were born through a cesarean section compared with the general population (p < 0.001). Medication during labor also differed, with higher rates of oxytocin (p < 0.001) and antibiotics (p = 0.008) administered to mothers of CH infants. A multivariate logistic regression model revealed an increased demand for oxytocin administration during the labor of a CH infant in a hypothyroidism severity-dependent manner, expressed as a threefold risk associated with permanent but not transient CH. Conclusions: Our findings of increased utilization of medical interventions during the labor and delivery of CH infants suggest that the prenatal fetal thyroid function may affect the development and progress of labor and delivery, in response to oxytocin.

Sucrose intake by rats affected by both intraperitoneal oxytocin administration and time of day.

Daily limited access to palatable food or drink at a fixed time is commonly used in rodent models of bingeing. Under these conditions, entrainment may modulate intake patterns. Oxytocin is involved in circadian patterns of intake and, when administered peripherally, reduces sucrose intake. However, oxytocin's effects on intake under limited-access conditions and its potential interaction with entrainment have not been explored. This study examined the role of entrainment on intake patterns, oxytocin's effects on sucrose intakes and locomotor activity and whether oxytocin's effects were mediated by its actions at the oxytocin receptor. Sated rats received daily 1-h access to 10% sucrose solution either at a fixed or varied time of day. Rats received intraperitoneal oxytocin (0mg/kg, 0.3mg/kg, 1mg/kg, 3mg/kg) prior to sucrose access, and spontaneous locomotor activity was assessed in an open-field test. Rats were then pre-treated with an oxytocin receptor antagonist, L368,899, prior to oxytocin before sucrose access. Intake patterns did not differ between fixed- or varied-time presentations; rats consumed more sucrose solution in the middle as opposed to the early-dark phase. Oxytocin dose-dependently reduced sucrose intakes, but also reduced locomotor activity. There was some evidence of partial blockade of oxytocin-induced sucrose intake reductions by L368,899, but the results were unclear. Time of day and oxytocin impact sucrose solution intake under daily limited access in rats and the sedative-like effects of oxytocin should be considered in future studies on oxytocin and food intake.

Effects of oxytocin and antagonist antidote atosiban on body weight and food intake of female mice, Mus musculus

Growing evidence suggests that oxytocin (OT) plays an important factor for the control of food intake, body weight, and energy metabolism in human and non-human animals. It has reported previously, the downregulation in oxytocin receptors (OTRs) expression is linked with the development of obesity, but exogenous OT reverse body weight and food intake in obese animal model. It is important to know that, whether intraperitoneal administration crosses blood brain barrier. Therefore, in the present experiment, we study the impact of intraperitoneal administration of synthetic OT 0.0116 mg/kg and antagonist atosiban (OTA) 1 mg/kg on food intake, and body weight of female mice, Mus musculus for different duration i.e. 30, 60, and 90 days. In this study, it was observed that there was significant decrease (p<0.001, one-way analysis of variance [ANOVA]) in the body weight (BW), food intake, and gonadosmatic indices (GSI) after the intraperitoneal exposure of OT at dose 0.0116 mg/kg up to 90 days and inhibits via antagonist atosiban. These results indicates that intraperitoneal administration of OT can be used for treatment for longer duration without any side effects and maintains homeostasis in physiologic system regulates body weight and gonadal weight in female mice, which represent an important therapeutic tool for the obesity and metabolic disorder in female.

Effect of intra-partum Oxytocin on neonatal encephalopathy: a systematic review and meta-analysis

BackgroundOxytocin is widely used for induction and augmentation of labour, particularly in low- and middle-income countries (LMICs). In this systematic review and meta-analysis, we examined the effect of intra-partum Oxytocin use on neonatal encephalopathy.MethodsThe protocol for this study was registered with PROSPERO (ID: CRD42020165049). We searched Medline, Embase and Web of Science Core Collection databases for papers published between January 1970 and May 2021. We considered all studies involving term and near-term (≥36 weeks’ gestation) primigravidae and multiparous women. We included all randomised, quasi-randomised clinical trials, retrospective studies and non-randomised prospective studies reporting intra-partum Oxytocin administration for induction and/or augmentation of labour. Our primary outcome was neonatal encephalopathy. Risk of bias was assessed in non-randomised studies using the Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool. The RoB 2.0 tool was used for randomised studies. A Mantel-Haenszel statistical method and random effects analysis model were used for meta-analysis. Odds ratios were used to determine effect measure and reported with 95% confidence intervals.ResultsWe included data from seven studies (6 Case-control studies, 1 cluster-randomised trial) of which 3 took place in high-income countries (HICs) and 4 in LMICs. The pooled data included a total of 24,208 women giving birth at or after 36 weeks; 7642 had intra-partum Oxytocin for induction and/or augmentation of labour, and 16,566 did not receive intra-partum Oxytocin. Oxytocin use was associated with an increased prevalence of neonatal encephalopathy (Odds Ratio 2.19, 95% CI 1.58 to 3.04; p < 0.00001).ConclusionsIntra-partum Oxytocin may increase the risk of neonatal encephalopathy. Future clinical trials of uterotonics should include neonatal encephalopathy as a key outcome.

Hindbrain Administration of Oxytocin Reduces Food Intake, Weight Gain and Activates Catecholamine Neurons in the Hindbrain Nucleus of the Solitary Tract in Rats.

Existing studies show that CNS oxytocin (OT) signaling is important in the control of energy balance, but it is unclear which neurons may contribute to these effects. Our goals were to examine (1) the dose-response effects of acute OT administration into the third (3V; forebrain) and fourth (4V; hindbrain) ventricles to assess sensitivity to OT in forebrain and hindbrain sites, (2) the extent to which chronic 4V administration of OT reduces weight gain associated with the progression of diet-induced obesity, and (3) whether nucleus tractus solitarius (NTS) catecholamine neurons are downstream targets of 4V OT. Initially, we examined the dose-response effects of 3V and 4V OT (0.04, 0.2, 1, or 5 μg). 3V and 4V OT (5 μg) suppressed 0.5-h food intake by 71.7 ± 6.0% and 60 ± 12.9%, respectively. 4V OT (0.04, 0.2, 1 μg) reduced food intake by 30.9 ± 12.9, 42.1 ± 9.4, and 56.4 ± 9.0%, respectively, whereas 3V administration of OT (1 μg) was only effective at reducing 0.5-h food intake by 38.3 ± 10.9%. We subsequently found that chronic 4V OT infusion, as with chronic 3V infusion, reduced body weight gain (specific to fat mass) and tended to reduce plasma leptin in high-fat diet (HFD)-fed rats, in part, through a reduction in energy intake. Lastly, we determined that 4V OT increased the number of hindbrain caudal NTS Fos (+) neurons (156 ± 25) relative to vehicle (12 ± 3). The 4V OT also induced Fos in tyrosine hydroxylase (TH; marker of catecholamine neurons) (+) neurons (25 ± 7%) relative to vehicle (0.8 ± 0.3%). Collectively, these findings support the hypothesis that OT within the hindbrain is effective at reducing food intake, weight gain, and adiposity and that NTS catecholamine neurons in addition to non-catecholaminergic neurons are downstream targets of CNS OT.

Oxytocin-induced anxiogenic behavior in juvenile male rats

ABSTRACT Oxytocin (OT) is considered beneficial to mental health owing to its anxiolytic, prosocial, and anti-stress effects; however, the adverse effects of OT have been controversial, such as its potentially anxiogenic actions. Although OT influences drug abuse and reciprocally affects vulnerability to drug use, the relationship between OT’s anxiogenic working and nicotine preference intake has not been clearly defined. To clarify this issue, the effect of acute peripheral administration of OT on anxiety and nicotine preference was investigated in juvenile male rats. Anxiogenic behaviors were noticeably increased in OT-administrated rats, with an increase in serum corticosterone levels. Moreover, increased anxiety-like behaviors and corticosterone levels were observed in the OT analog carbetocin-injected rats. In the nicotine preference test, the rats’ aversive responses to initial nicotine choice and preference were not significantly different between saline-injected and OT-injected rats. However, when administered with OT, there was a significant negative correlation between anxiety-like behavior and low-dose nicotine consumption. Collectively, these results provide evidence that acute OT exposure could induce anxiogenic behavior with corticosterone augmentation, contributing to the attenuation of nicotine preference. This suggests that both aspects of OT, as well as their benefits and drawbacks, should be considered.

Prediction of successful trial of labor after cesarean among grand-multiparous women.

To determine the factors associated with successful trial of labor after cesarean (TOLAC) among grand-multiparous (GMP) women. A retrospective cohort study was conducted, including all GMP women (≥ 5 deliveries) undergoing TOLAC during 3/2011 and 6/2020, delivering a singleton cephalic newborn. Factors associated with successful vaginal delivery were examined by multivariable analysis. Overall, 381/413 (92.2%) GMP succeeded TOLAC. Maternal characteristics did not differ between TOLAC success and TOLAC failure groups. Previous cesarean delivery characteristics did not differ between study groups. The median number of previous vaginal births after cesarean was 2 [interquartile range 1-4]. Gestational age at TOLAC was lower in the success group (mean 371/7 ± 36/7 vs. 385/7 ± 31/7weeks, p = 0.028). A lower rate of modified Bishop score < 4 was associated with TOLAC success [149 (39.1%) vs. 22 (69%), odds ratio (OR) 95% confidence interval (CI) 0.29 (0.13-0.64), p = 0.001]. The rate of induction of labor was higher in the TOLAC failure group [120 (31.5%) vs. 17 (53%), OR 95% CI 0.40 (0.19-0.83), p = 0.013]. The rate of oxytocin administration was higher in the TOLAC failure group [94 (24.7%) vs. 15 (47%) OR (95% CI) 0.37 (0.17-0.77), p = 0.006]. The duration of rupture of membranes was negatively associated with TOLAC success. Neonatal and maternal adverse outcomes did not differ between study groups. In multivariable logistic regression analysis, only the duration of rupture of membranes and modified Bishop score < 4 were independently associated with TOLAC success [adjusted OR (95% CI) 0.98 (0.96-0.99), p = 0.027 and 0.40 (0.16-0.97), p = 0.044]. TOLAC among GMP has a very-high success rate. Shortening the duration of ruptured membranes is a modifiable factor that may be associated with increased TOLAC success rates.

Oxytocin induces lordosis behavior in female rats through the prostaglandin E2/GnRH signaling system

Intracerebroventricular (icv) administration of oxytocin (OT) induces robust lordosis behavior (lordosis quotient and lordosis intensity) in estrogen-primed rats. The present study explored the hypothesis that the OT-Prostaglandin E2-GnRH pathway (a pathway produced in astrocytes) is involved in the facilitation of lordosis behavior by icv infusion of OT (2 μg). In Experiment 1, we tested the involvement of the OT receptor (OTR) by infusion of the OTR antagonist, atosiban (ATO). OT-induced lordosis was significantly reduced at both 30 and 120 min by prior infusion of ATO. In Experiment 2, we studied the effects of aspirin (COX2 inhibitor) and ONO-AE3-208 (ONO; EP4 prostaglandin receptor antagonist) on OT-induced lordosis. Infusions of both compounds diminished OT-induced lordosis at both 120 and 240 min. In Experiment 3, the involvement of the GnRH-1 receptor inhibitor antide on OT-induced lordosis was evaluated. Antide significantly inhibited OT-induced lordosis at all times tested. These data indicate that the OT/PGE2/GnRH pathway is involved in the expression of OT-induced lordosis behavior, an effect that may be occurring directly in hypothalamic astrocytes.

Oxytocin and vasopressin in male forensic psychiatric patients with personality disorders and healthy controls

ABSTRACT Oxytocin and vasopressin are neuropeptides implicated as modulators of human aggressive behavior. In animal models, administration of oxytocin generally attenuates aggressive behavior, but in humans the effects of oxytocin appear to be more nuanced. Vasopressin seems to have an opposing influence on aggression in animal studies, but much less research has been done in humans. We performed a cross-sectional study in which we measured oxytocin and vasopressin levels in forensic psychiatric male patients with a personality disorder (N = 38) and healthy male controls (N = 108). Elevated salivary oxytocin (B = −0.10, P = 0.02) and reduced urinary vasopressin (B = 0,19, P < 0.01) levels were found in patients compared to controls. Within the patient group urinary oxytocin levels were positively associated with psychopathy scores as measured with the PCL-R (B = 0.02, P = 0.02). These findings suggest that baseline levels in forensic psychiatric patients diagnosed with a primary personality disorder might be counterintuitive, as oxytocin levels are higher than expected and vasopressin levels are lower than those of healthy controls. More generally, the results imply a complex role of these neuropeptides on human behavior, in line with the social salience theory.

Protective Effect of Oxytocin on Ventilator-Induced Lung Injury Through NLRP3-Mediated Pathways.

Mechanical ventilation is an indispensable life-support treatment for acute respiratory failure in critically ill patients, which is generally believed to involve uncontrolled inflammatory responses. Oxytocin (OT) has been reported to be effective in animal models of acute lung injury. However, it is not clear whether Oxytocin has a protective effect on ventilator-induced lung injury (VILI). Therefore, in this study, we aimed to determine whether OT can attenuate VILI and explore the possible mechanism of this protection. To this end, a mouse VILI model was employed. Mice were pretreated with OT 30 min before the intraperitoneal injection of saline or nigericin and ventilation for 4 h, after which they were euthanized. Pathological changes, lung wet/dry (W/D) weight ratio, myeloperoxidase (MPO) activity, the levels of inflammatory cytokines [i.e., interleukin (IL)-1β, IL-6, and IL-18] in lung tissues and bronchoalveolar lavage fluid (BALF), and expression of NLRP3, Toll-like receptor 4 (TLR4), caspase-1, nuclear factor (NF)-κB, and GSDMD in lung tissues were measured. OT treatment could reduce pathological injury, the W/D ratio, and MPO activity in VILI mice. Our data also indicated that OT administration alleviated the expression of TLR4/My-D88 and the activation of NF-κB, NLRP3, and caspase-1 in lung tissues from the VILI mice model. Furthermore, OT also decreased the levels of IL-1β, IL-6, and IL-18 in the bronchoalveolar lavage fluid. Moreover, the OT administration may alleviate the activation of GSDMD partially through its effects on the NLRP3-mediated pathway. Collectively, OT exerted a beneficial effect on VILI by downregulating TLR4-and NLRP3-mediated inflammatory pathways.

A survey of anaesthetists on uterotonic usage practices for elective caesarean section in Australia and New Zealand.

Prophylactic administration of uterotonics ensures adequate uterine contraction at elective caesarean section to prevent substantial haemorrhage. Royal College of Obstetricians and Gynaecologists guidelines advise the administration of oxytocin at 5 IU as a 'slow bolus' but there are variations in clinical practice. This study aimed to determine the beliefs and uterotonic usage practices at elective caesarean section by surveying anaesthetist members of the Obstetric Anaesthesia Special Interest Group in Australia and New Zealand. Questionnaires were emailed to Obstetric Anaesthesia Special Interest Group members and the response rate was 33%, with analysis of 279 completed reports. Oxytocin was the most commonly used first-line uterotonic, but extensive variation in oxytocin bolus use was identified. Thirty-eight per cent of anaesthetists routinely administered Royal College of Obstetricians and Gynaecologists guideline-recommended 5 IU, whereas 38% favoured low dose (<5 IU), 10% high dose (≥10 IU) oxytocin and 13% carbetocin (100 µg). More than 50% felt the evidence was weak for guideline-recommended 5 IU. Wide variation in the duration of oxytocin administration was also identified. Fifty-eight per cent of anaesthetists routinely gave follow-up oxytocin infusions, most commonly at 40 IU over 4 hours, but there was significant variation in the dosage (10-40 IU) and administration duration (1 hour to ≥6 hours). In conclusion, there is significant variation in oxytocin usage practices at elective caesarean section among Australian and New Zealand anaesthetists. This variation may be due to a lack of strong evidence to guide practice. This emphasises the need for high quality trials in this clinically important area.

The importance of pro-social processing, and ameliorating dysfunction in schizophrenia. An FMRI study of oxytocin

Schizophrenia is often a severe and debilitating mental illness, frequently associated with impairments in social cognition that hinder individuals' abilities to relate to others and integrate effectively in society. Oxytocin has emerged as a putative therapeutic agent for treating social deficits in schizophrenia, but the mode of action remains unclear. This placebo-controlled crossover study aimed to elucidate the neural underpinnings of oxytocin administration in patients with schizophrenia. 20 patients with schizophrenia were examined using functional magnetic resonance imaging under oxytocin (40 IU) or placebo nasal spray. Participants performed a stochastically rewarded decision-making task that incorporated elements of social valence provided by different facial expressions, i.e. happy, angry and neutral. Oxytocin attenuated the normal bias in selecting the happy face accompanied by reduced activation in a network of brain regions that support mentalising, processing of facial emotion, salience, aversion, uncertainty and ambiguity in social stimuli, including amygdala, temporo-parietal junction, posterior cingulate cortex, precuneus and insula. These pro-social effects may contribute to the facilitation of social engagement and social interactions in patients with schizophrenia and warrant further investigation in future clinical trials for social cognitive impairments in schizophrenia.

Transcriptional profiling of equine endometrium before, during and after capsule disintegration during normal pregnancy and after oxytocin-induced luteostasis in non-pregnant mares.

The current study used RNA sequencing to determine transcriptional profiles of equine endometrium collected 14, 22, and 28 days after ovulation from pregnant mares. In addition, the transcriptomes of endometrial samples obtained 20 days after ovulation from pregnant mares, and from non-pregnant mares which displayed and failed to display extended luteal function following the administration of oxytocin, were determined and compared in order to delineate genes whose expressions depend on the presence of the conceptus as opposed to elevated progesterone alone. A mere fifty-five transcripts were differentially expressed between samples collected from mares at Day 22 and Day 28 of pregnancy. This likely reflects the longer-term exposure to a relatively constant, progesterone-dominated environment with little change in factors secreted by the conceptus that would affect endometrial gene expression. The complement system was amongst the canonical pathways significantly enriched in transcripts differentially expressed between Day 14 and Day 22/28 of pregnancy. The expression of complement components 7 and 8 was confirmed using in situ hybridization. The expression of SERPING1, an inhibitor of the complement system, was confirmed by immunohistochemistry. In line with the resumed capacity of the endometrium to produce prostaglandin, prostaglandin G/H synthase 1 was expressed at higher levels at Days 22 and 28 than at Day 14 of pregnancy. Our data suggest that this up-regulation is enhanced by the presence of the conceptus; samples obtained from mares at Day 20 of pregnancy had significantly higher levels of prostaglandin G/H synthase 1 transcript than mares with extended luteal function.

Prevention of retained fetal membranes and improvement in subsequent fertility with oxytocin administration in cows with assisted calving

In dairy cows, the efficacy of oxytocin treatment for preventing retained fetal membranes (RFM) is controversial. The physiological condition of cows associated with the calving process may affect the action of oxytocin. This study aimed to elucidate the difference in the efficacy of exogenous oxytocin treatment immediately after calving among cows that received various obstetric interventions. The calving ease was recorded using a score of 1–5, and assisted birth was defined as a score of 2 or more. Cows that required calving assistance (assisted, n = 28) due to delayed calving progression had a prolonged time from calving to expulsion of the fetal membrane (P < 0.01), and impaired reproductive performance compared to cows that did not receive calving assistance (unassisted, n = 78). The effect of oxytocin treatment was determined using cows that did not expel their fetal membrane within 3 h after calving. Cows were randomly divided into the control (unassisted, n = 41; assisted, n = 22) or oxytocin group (unassisted, n = 33; assisted, n = 10). Oxytocin (50 IU) was administered intramuscularly to the cows in the oxytocin group between 3 and 6 h after calving, while no treatment was administered in the control group. In cows with assisted birth, oxytocin administration accelerated placental expulsion (P < 0.05) and improved several reproductive parameters, such as the number of services until conception (P < 0.05) and the calving to conception intervals (P < 0.05) compared to the control group. On the other hand, oxytocin administration slightly accelerated placental expulsion (P < 0.05), but failed to improve fertility in cows with unassisted birth. The results indicate that the action of oxytocin varies depending on the calving situation of the cows. Oxytocin administration during the early postpartum period could prevent RFM and improve the decline in reproductive performance associated with calving assistance.

6.14 Randomized, Placebo-Controlled Trial With Open-Label Extension of Intranasal Oxytocin for Autism Spectrum Disorder

The neuropeptide oxytocin (OXT) plays an important role in human social behaviors. There is growing interest in the use of OXT for mental health conditions characterized by social impairment. Studies of adult populations with autism spectrum disorder (ASD) have shown promising responses in social cognition, quality of life, and repetitive behaviors. To date, few studies have examined the safety and tolerability of the sustained use of OXT in a pediatric population with ASD. None have comprehensively elicited adverse events, monitored cardiac function, or collected routine blood chemistries in a systematic way to evaluate the safety of intranasal OXT. In order to investigate the safety, tolerability, and potential efficacy of sustained, daily administration of OXT in children with ASD, we conducted a randomized, double-blind, placebo-controlled crossover pilot study in 25 youths aged 3 to 17 years. Intranasal administration of flexibly dosed oxytocin or placebo was provided for 8 weeks; then an additional 8 weeks of open-label oxytocin was given to all participants. All screened participants (n = 27) were recruited through the University of North Carolina at Chapel Hill. OXT treatment was well tolerated with the exception of a single subject. One in 12 subjects randomized to OXT discontinued during blind treatment, and 2 in 24 discontinued during open treatment. Adverse events were comparable between the oxytocin and placebo groups. All safety assessments including EEG and blood chemistry revealed no clinically significant differences between OXT and placebo. Secondary efficacy assessments indicated that significant within-group changes were observed after 8 weeks on the Aberrant Behavior Checklist (ABC)-Social Withdrawal, ABC-Irritability, and ABC-Stereotypy subscales (3 variables: all p < 0.05) in the OXT group. Findings in this study must be interpreted in the context of several limitations. Most prominent are the small sample size and multiple assessments. The primary goal of this study was to evaluate the safety and tolerability of a treatment that may be used for months if not years in a pediatric population. Our small pilot sample would likely miss uncommon but serious adverse events. Future studies must be powered and of sufficient duration to explore the long-term safety and tolerability of OXT.

Measuring Affinity of Ligands to the Oxytocin Receptor Using Radioligand Binding.

Two aims of oxytocin receptor (OTR)-targeted drug discovery are development of selective OTR-binding PET tracers and development of brain-permeable selective OTR agonists. By allowing measurement of central OTR binding site occupancy after administration of intranasal oxytocin, OTR PET tracers inform anunderstanding of the conflicting effects on pro-social behaviors seenwith administration of intranasal oxytocin in human studies. By mitigating pharmacokinetic and pharmacodynamic limitations of intranasal oxytocin, development of brain-permeable selective OTR agonists may produce therapies for mental disorders that involve asocial symptoms. A key step in development of new OTR-targeting PET radioligands and small molecule agonists is measurement of OTR affinity. One technique that can quantitate the affinity of candidate ligands for the OTR is competition radioligand binding. This chapter describes the materials, methods, and considerations of experimental design required to conduct the steps of competition radioligand binding for OTR drug discovery.

The Role of Oxytocin in Social Circuits and Social Behavior in Dementia.

Administration of intranasal oxytocin has been found to improve social cognition in a number of brain conditions, including autism spectrum disorder and schizophrenia. Whether this approach is relevant in dementias is currently unknown, particularly in frontotemporal dementia, a younger-onset dementia characterized clinically by marked changes in social cognition and behavior and focal atrophy of the frontal and temporal lobes. This chapter provides an overview of the deficits in social cognition in frontotemporal dementia and reviews the emerging evidence of intranasal oxytocin administration as a potential treatment option for these deficits. Future research directions will also be discussed.