Effects Of Oxytocin Research Articles

Oxytocin in old age psychiatry: A systematic review of the safety of using intranasal oxytocin in older adults.

To examine the literature for evidence of adverse events associated with the use of intranasal oxytocin in older adults (60+). A systematic review was undertaken according to PRISMA guidelines. Peer-reviewed literature was searched for studies involving intranasal oxytocin use in older populations. The Joanna Briggs Institute's (JBI) critical appraisal tool was used to assess the quality of included studies. The search identified nine randomized controlled trials (RCTs) that investigated the effects of intranasal oxytocin on a total sample size of 331 older participants. Adverse effects associated with oxytocin administration were predominantly mild and varied inconsistently between studies. Compared to placebo intranasal oxytocin was not significantly associated with severe adverse outcomes in doses ranging from 24 to 72 IU after single dose and or repeated doses in the short-term. In a population of older adults, intranasal oxytocin is devoid of serious adverse events. Although this review offers valuable insights, it may not fully reflect the potential adverse events associated with the long-term administration of intranasal oxytocin such as would be expected in its clinical application if approved for the treatment of dementia.

Oxytocin, the Love Hormone, in Stem Cell Differentiation

Oxytocin (OXT) is a neurohypophysial nonapeptide that exerts its effects mainly through the oxytocin receptor (OXTR). Several studies have pointed out the role of OXT in the modulation of stem cell (SC) fate and properties. SCs are undifferentiated cells characterized by a remarkable ability to self-renew and differentiate into various cell types of the body. In this review, we focused on the role of OXT in SC differentiation. Specifically, we summarize and discuss the scientific research examining the effects of OXT on mesodermal SC-derived lineages, including cardiac, myogenic, adipogenic, osteogenic, and chondrogenic differentiation. The available studies related to the effects of OXT on SC differentiation provide little insights about the molecular mechanism mediated by the OXT–OXTR pathway. Further research is needed to fully elucidate these pathways to effectively modulate SC differentiation and develop potential therapeutic applications in regenerative medicine.

Sympathetic Innervation of Interscapular Brown Adipose Tissue Is Not a Predominant Mediator of Oxytocin-Induced Brown Adipose Tissue Thermogenesis in Female High Fat Diet-Fed Rats.

Recent studies have indicated that hindbrain [fourth ventricle (4V)] administration of the neurohypophyseal hormone, oxytocin (OT), reduces body weight, energy intake and stimulates interscapular brown adipose tissue temperature (TIBAT) in male diet-induced obese (DIO) rats. What remains unclear is whether chronic hindbrain (4V) OT can impact body weight in female high fat diet-fed (HFD) rodents and whether this involves activation of brown adipose tissue (BAT). We hypothesized that OT-elicited stimulation of sympathetic nervous system (SNS) activation of interscapular brown adipose tissue (IBAT) contributes to its ability to activate BAT and reduce body weight in female high HFD-fed rats. To test this hypothesis, we determined the effect of disrupting SNS activation of IBAT on OT-elicited stimulation of TIBAT and reduction of body weight in DIO rats. We first measured the impact of bilateral surgical SNS denervation to IBAT on the ability of acute 4V OT (0.5, 1, and 5 µg ≈ 0.5, 0.99, and 4.96 nmol) to stimulate TIBAT in female HFD-fed rats. We found that the high dose of 4V OT (5 µg ≈ 4.96 nmol) stimulated TIBAT similarly between sham rats and denervated rats (p = NS). We subsequently measured the effect of bilateral surgical denervation of IBAT on the effect of chronic 4V OT (16 nmol/day ≈ 16.1 μg/day) or vehicle infusion to reduce body weight, adiposity and energy intake in female HFD-fed rats (N = 7-8/group). Chronic 4V OT reduced body weight gain (sham: -18.0 ± 4.9 g; denervation: -15.9 ± 3.7 g) and adiposity (sham: -13.9 ± 3.7 g; denervation: -13.6 ± 2.4 g) relative to vehicle treatment (p < 0.05) and these effects were similar between groups (p = NS). These effects were attributed, in part, to reduced energy intake evident during weeks 2 (p < 0.05) and 3 (p < 0.05). To test whether these results translate to other female rodent species, we also examined the effect of chronic 4V infusion of OT on body weight and adiposity in two strains of female HFD-fed mice. Similar to what we found in the HFD-fed rat model, we also found that chronic 4V OT (16 nmol/day) infusion resulted in reduced body weight gain, adiposity and energy intake in female DIO C57BL/6J and DBA/2J mice (p < 0.05 vs. vehicle). Together, these findings suggest that (1) sympathetic innervation of IBAT is not necessary for OT-elicited increases in BAT thermogenesis and weight loss in female HFD-fed rats and (2) the effects of OT to reduce weight gain and adiposity translate to other female mouse models of diet-induced obesity (DIO).

Effects of oxytocin receptor agonists on hair growth promotion

Oxytocin has various effects ranging from promoting labor in pregnant women to alleviating stress. Recently, we reported the hair growth-promoting effects of oxytocin in hair follicle organoids. However, its clinical application faces challenges such as rapid degradation in vivo and poor permeability due to its large molecular weight. Therefore, in this study, we investigated the effects of the oxytocin receptor (OXTR) agonists WAY267464 and LIT001 as alternatives to oxytocin on hair growth. Human dermal papilla (DP) cells were cultured in WAY267464 or LIT001-supplemented medium. The addition of WAY267464 and LIT001 increased the expression of hair growth-related genes in DP cells. We tested the hair growth-promoting effects of WAY267464 and LIT001 using hair follicle organoids in vitro and found that they significantly promoted hair follicle sprouting. Thus, our findings indicate that WAY267464 and LIT001 are potential hair growth agents and may encourage further research on the development of novel hair growth agents targeting OXTR in patients with alopecia.

The Impact of Labor Oxytocin Use on Newborn Liver Enzymes.

Oxytocin is commonly used during labor and delivery for induction of labor and prevention of postpartum hemorrhage. While previous studies have explored the effects of labor oxytocin use on maternal and neonatal outcomes, there is a paucity of research on its impact on newborn liver enzyme function. This study aimed to assess the effects of labor oxytocin use on liver enzyme function in newborns. A case-control study was conducted. The case group consisted of 70 newborns whose mothers received oxytocin during labor, while the control group consisted of 70 newborns whose mothers did not receive oxytocin. Complete blood count (CBC), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total and indirect bilirubin levels were measured in all newborns on the second day of life. The levels of AST and total and indirect bilirubin were found to be higher in the case group than in the control group (51 vs. 42, 7.8 vs. 4.6, and 7.4 vs. 4, respectively; p < 0.005). The levels of CPK and LDH were also higher in the case group (p < 0.005). However, the difference in ALT levels was not significant between the study groups. The observed increase in liver enzymes in this study can indicate the effect of maternal oxytocin on the newborn's liver function. While the changes in liver enzyme levels due to oxytocin use were not found to be high enough to cause liver damage, the increase in CPK and LDH levels could potentially elevate bilirubin levels due to hemolysis. Further research is needed to confirm these findings and explore the underlying mechanisms.

Oxytocin/Oxytocin Receptor Signalling in the Gastrointestinal System: Mechanisms and Therapeutic Potential.

The neuropeptide hormone oxytocin (OT) is involved in various physiological and pathological processes via the oxytocin receptor (OTR). While OT is most widely known as a reproductive system hormone and a nervous system neurotransmitter, the OT/OTR system has gradually gained much attention for its role in the gastrointestinal (GI) system, such as the GI motility, secretion, and bowel inflammatory reactions. Its importance in GI cancers has also been reported in the past few decades. The promising clinical observations have revealed OT's anti-nociceptive effect, protective effect over gut injury, and the potential of using microbiota to naturally increase endogenous OT levels, which shed a light on the management of GI disorders with lower side effects. However, no current comprehensive review is available on the actions of OT/OTR in the GI tract. This review aims to present the lesser-known role of the OT/OTR system in the GI tract, and the most recent findings are discussed regarding the distribution and functional role of OTR signalling in regulating (patho)physiological functions of the GI tract. Special emphasis is placed on its therapeutic potential for clinical management of GI disorders, such as GI pain, inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS). The recent characterisation of the OTR's crystal structure has advanced research for designing and identifying new OTR-specific molecules. Future in-depth basic and clinical research is needed to further elucidate the involvement and detailed mechanism of OT/OTR in GI disorders, and the development of OTR-specific ligands.

Modulatory effects of oxytocin on normal human cultured melanocyte proliferation, migration, and melanogenesis

Melanocytes are specialized melanin-producing neural crest-derived cells. Melanocyte proliferation and melanin production (i.e., melanogenesis) are crucial for determining skin color. Disruption of these processes can cause pigmentary skin disorders, including hypo-pigmentary disorders such as vitiligo and hyper-pigmentary disorders such as melasma. Understanding these processes is important for discovering new targets to tackle these skin disorders. Therefore, this study aimed to investigate the effects of oxytocin (OXT) on melanocyte functions. Normal Human Cultured Melanocytes (NHCM) were treated with different OXT doses to investigate OXT effects and mechanisms on NHCM proliferation, migration, and on melanogenesis. OXT significantly increased NHCM proliferation and migration in a dose-dependent manner after 72 h of treatment. In addition, OXT dose-dependently upregulated melanogenesis-related microphtalmia-associated transcription factor, tyrosinase, tyrosinase-related protein (TYRP)-1, and TYRP-2 expression accompanied by an increased trend in melanosome number and maturation stage. Furthermore, OXT at concentrations (62.5–125 nM) increased melanin production. These findings suggest the involvement of OXT receptor (OXTR). In addition, this study demonstrates that OXT stimulates melanocyte proliferation, migration, with a tendency toward melanosome maturation, while it modulates melanin production in a dose-dependent manner. Thus, OXT system including its receptor OXTR may be a potential therapeutic target for skin pigmentary disorders.

Maternal mind-mindedness and infant oxytocin are interrelated and negatively associated with postnatal depression.

Previous studies show that maternal mind-mindedness positively impacts children's social development. In the current studies, we examine the relation between mind-mindedness during parent-child interaction, oxytocin (OT), and postnatal depression in a sample of mothers (N = 62, ages 23-44) and their infant (ages 3-9 months). In Study 1, infant salivary OT was positively correlated with mothers' appropriate mind-related comments, and negatively correlated (at trend level) with maternal depression scores. Mothers experiencing symptoms of depression used fewer appropriate mind-related comments than controls. Study 2 was a double-blind, placebo-controlled, experimental study, in which the same women who participated in Study 1 were administered nasal OT. This did not significantly influence levels of mind-mindedness. Study 2 warrants a larger trial to investigate the effect of OT on mind-mindedness further. Study 1 is the first to demonstrate an association between maternal mind-mindedness and variation in children's OT levels. Since both OT and mind-mindedness have been repeatedly implicated in processes of maternal-infant attachment, this association highlights the centrality of mothers' caregiving representations in facilitating the parent-child relationship and children's early development.

Oxytocin and Vasopressin in Emotional Memory and “Face Reading”: a Neurobiological Approach and Clinical Aspects

The ability to adequately perceive and recognize emotions is a key and universal tool in interpersonal communication, which allows people to understand feelings, intentions, and emotional reactions of themselves and others. Throughout their life, people have to make inferences about mental state of others by interpreting subtle social signals, such as facial expressions, to understand or predict others’ behavior, which is crucial in constructive social interactions. Therefore, emotional memory associated with the ability to identify emotions based on one’s life experience is the cornerstone of social cognition and interpersonal relationships. Oxytocin and vasopressin are neurohypophysial peptides that have attracted scientific attention due to their role in the emotional and social aspects of behavior. Variable and contrasting effects of oxytocin and vasopressin may be related to the sites of the brain where they exert their activity. Aim. This review aimed to evaluate neural mechanisms underlying oxytocin-mediated and vasopressin-mediated modulation of emotional memory; to assess how cerebral oxytocin-signal and vasopressin-signal transduction mediates emotional and social behavior; to discuss the role of the two neuropeptides in non-verbal interpersonal communication; and to present their cerebral effects in relation to an ability for “face reading” in patients with mental disorders.

Could intranasal oxytocin enhance the effects of psychotherapy in individuals with mental disorders? A systematic review and meta-analysis

Interest in the therapeutic potential of oxytocin for the treatment of mental health disorders, especially those involving social dysfunction, has increased considerably in recent years. To date, most studies have only evaluated oxytocin as monotherapy, with highly inconsistent results. A new line of research is exploring the effects of combining oxytocin with psychotherapy. The aim of the present review was to evaluate the therapeutic effects of intranasal oxytocin combined with psychotherapy in individuals with psychiatric disorders. Only randomized clinical trial design was eligible for inclusion. A search of relevant databases yielded 2480 articles published through April 30, 2024. Of these, 13 trials (518 participants) were included in this review and 4 of them in a meta-analysis. The trials evaluated a range of different psychotherapeutic interventions, oxytocin doses, and mental disorders. Overall, the trials suggested that combined treatment reduced negative mental representations, decreased stress, and increased therapeutic alliance. Meta-analysis showed that combined treatment significantly reduced depressive symptoms (d= −1.58, 95 % CI: −3.15 to −0.01). However, the treatment with oxytocin had no significant effects on psychiatric symptoms (d= 0.00, 95 % CI: −0.56–0.57) or social functioning (d = 0.21, 95 % CI: −0.07–0.49). Limitations included the heterogeneity and limited sample sizes of the trials. The findings suggest that the combination of intranasal oxytocin and psychotherapy may be an effective therapeutic approach to reduce depressive symptoms in individuals with mental disorders and may improve retention and therapeutic alliance.

Effects of systemic oxytocin and beta-3 receptor agonist (CL 316243) treatment on body weight and adiposity in male diet-induced obese rats.

Previous studies have implicated hindbrain oxytocin (OT) receptors in the control of food intake and brown adipose tissue (BAT) thermogenesis. We recently demonstrated that hindbrain [fourth ventricle (4V)] administration of oxytocin (OT) could be used as an adjunct to drugs that directly target beta-3 adrenergic receptors (β3-AR) to elicit weight loss in diet-induced obese (DIO) rodents. What remains unclear is whether systemic OT can be used as an adjunct with the β3-AR agonist, CL 316243, to increase BAT thermogenesis and elicit weight loss in DIO rats. We hypothesized that systemic OT and β3-AR agonist (CL 316243) treatment would produce an additive effect to reduce body weight and adiposity in DIO rats by decreasing food intake and stimulating BAT thermogenesis. To test this hypothesis, we determined the effects of systemic (subcutaneous) infusions of OT (50 nmol/day) or vehicle (VEH) when combined with daily systemic (intraperitoneal) injections of CL 316243 (0.5 mg/kg) or VEH on body weight, adiposity, food intake and brown adipose tissue temperature (T IBAT ). OT and CL 316243 monotherapy decreased body weight by 8.0±0.9% ( P <0.05) and 8.6±0.6% ( P <0.05), respectively, but OT in combination with CL 316243 produced more substantial weight loss (14.9±1.0%; P <0.05) compared to either treatment alone. These effects were associated with decreased adiposity, energy intake and elevated T IBAT during the treatment period. The findings from the current study suggest that the effects of systemic OT and CL 316243 to elicit weight loss are additive and appear to be driven primarily by OT-elicited changes in food intake and CL 316243-elicited increases in BAT thermogenesis.

Peptides are cardioprotective drugs of the future. Oxytocin

The widespread introduction of percutaneous coronary intervention (PCI) in the treatment of acute myocardial infarction (AMI) caused a significant reduction in the mortality rate from AMI in developed countries. However, over the past 10 years, there was no significant reduction in in-hospital mortality from AMI. It is clear that there is an urgent need to develop novel drugs that could effectively prevent reperfusion injury of the heart after successful recanalization of the infarct-related coronary artery. Enzyme-resistant peptide agonists of the oxytocin receptor could become a prototype for the creation of such drugs. It was shown oxytocin could selectively prevent cardiac reperfusion injury. The cardioprotective effect of oxytocin in coronary artery occlusion and myocardial reperfusion is distinguished by a decrease in infarct size, an improvement in cardiac contractility, and a decrease in the incidence of ventricular arrhythmias. In addition, oxytocin inhibits apoptosis and pyroptosis of cardiomyocytes in hypoxia/reoxygenation. It has been established that kinases, NO-synthase, and guanylyl cyclase are involved in an oxytocininduced increase in cardiac resistance to ischemia / reperfusion.

Oxytocin effects on socially transmitted food preferences are moderated by familiarity between rats.

In the socially transmitted food preference (STFP) paradigm, rats change their preference for food rewards after socially interacting with a conspecific who has been fed with the originally non-preferred food. Here, we asked if oxytocin (OXT), a neuropeptide known for its role in social affiliation and social behavior, plays a role in STFP. Since OXT's influences on social behavior can be familiarity-dependent, we further asked if OXT effects on STFP are moderated by the familiarity between rats. Does OXT modulate rats' socially transmitted food choices in a familiarity-dependent way. We systemically injected either vehicle, low-dose (0.25mg/kg) of OXT, or large-dose (1.0mg/kg) of OXT before social interaction with either a familiar cagemate (in-group) or an unfamiliar conspecific from a different cage (out-group). We found an intergroup bias in STFP: vehicle-treated rats showed larger socially transmitted changes in food preference in the out-group than the in-group condition. OXT modulated STFP in a familiarity-dependent way: OXT prevented the increase in the consumption of the non-preferred food in the out-group, and decreased the consumption of the preferred food in the in-group. These effects were dose-dependent and observed under acute OXT action, but also on the subsequent day when acute OXT effects dissipated, suggesting long-lasting social learning effects of OXT. Additional analyses suggest that the familiarity and dose-dependent effects of OXT on STFP cannot be attributed to OXT's anorexic actions or differences in the duration of the social interactions. OXT modulates STFP in a familiarity-dependent way.

Effects of intranasal oxytocin on fear extinction learning.

Once a threat no longer exists, extinction of conditioned fear becomes adaptive in order to reduce allotted resources towards cues that no longer predict the threat. In anxiety and stress disorders, fear extinction learning may be affected. Animal findings suggest that the administration of oxytocin (OT) modulates extinction learning in a timepoint-dependent manner, facilitating extinction when administered prior to fear conditioning, but impairing it when administered prior to extinction learning. The aim of the present study was to examine if these findings translate into human research. Using a randomized, double-blind, placebo-controlled, 2-day fear conditioning and extinction learning design, behavioral (self-reported anxiety), physiological (skin conductance response), neuronal (task-based and resting-state functional magnetic resonance imaging), and hormonal (cortisol) data were collected from 124 naturally cycling (taking no hormonal contraceptives) healthy females. When administered prior to conditioning (Day 1), OT, similar to rodent findings, did not affect fear conditioning, but modulated the intrinsic functional connectivity of the anterior insula immediately after fear conditioning. In contrast to animal findings, OT impaired, not facilitated, extinction learning on the next day and increased anterior insula activity. When administered prior to extinction learning (day 2), OT increased the activity in the bilateral middle temporal gyrus, and similar to animal findings, reduced extinction learning. The current findings suggest that intranasal OT impedes fear extinction learning in humans regardless of the timepoint of administration, providing new insights and directions for future translational research and clinical applications.

Sympathetic innervation of interscapular brown adipose tissue is not a predominant mediator of OT-elicited reductions of body weight gain and adiposity in male diet-induced obese rats.

Recent studies indicate that central administration of oxytocin (OT) reduces body weight (BW) in high fat diet-induced obese (DIO) rodents by reducing energy intake and increasing energy expenditure (EE). Previous studies in our lab have shown that administration of OT into the fourth ventricle (4V; hindbrain) elicits weight loss and stimulates interscapular brown adipose tissue temperature (TIBAT) in DIO rats. We hypothesized that OT-elicited stimulation of sympathetic nervous system (SNS) activation of IBAT contributes to its ability to activate BAT and reduce BW in DIO rats. To test this, we determined the effect of disrupting SNS activation of IBAT on OT-elicited stimulation of TIBAT and reduction of BW in DIO rats. We first confirmed that bilateral surgical SNS denervation to IBAT was successful based on having achieved ≥ 60% reduction in IBAT norepinephrine (NE) content from DIO rats. NE content was selectively reduced in IBAT by 94.7 ± 2.7, 96.8 ± 1.8 and 85.9 ± 6.1% (P<0.05) at 1, 6 and 7-weeks post-denervation, respectively, and was unchanged in liver or inguinal white adipose tissue. We then measured the impact of bilateral surgical SNS denervation to IBAT on the ability of acute 4V OT (1, 5 μg) to stimulate TIBAT in DIO rats. We found that the high dose of 4V OT (5 μg) stimulated TIBAT similarly between sham and denervated rats (P=NS) and that the effects of 4V OT to stimulate TIBAT did not require beta-3 adrenergic receptor signaling. We subsequently measured the effect of bilateral surgical denervation of IBAT on the effect of chronic 4V OT (16 nmol/day) or vehicle infusion to reduce BW, adiposity and energy intake in DIO rats. Chronic 4V OT reduced BW gain by -7.2 ± 9.6 g and -14.1 ± 8.8 g in sham and denervated rats (P<0.05 vs vehicle treatment), respectively, and this effect was similar between groups (P=NS). These effects were associated with reductions in adiposity and energy intake (P<0.05). Collectively, these findings support the hypothesis that sympathetic innervation of IBAT is not required for central OT to increase BAT thermogenesis and reduce BW gain and adiposity in male DIO rats.

Epistatic interactions between oxytocin- and dopamine-related genes and trust.

Trust is an essential human trait. Although research suggests that the interplay between oxytocinergic and dopaminergic systems affects trust formation, little research has focused on epistatic (i.e., gene by gene) interaction effects of oxytocin- and dopamine-related genes on trust. Using a sample of 348 adults (114 men), we aimed to investigate the associations between genetic variants in oxytocin- and dopamine-related genes and the general, neighborhood, and institutional trust with consideration of sex differences. Three-way interaction between oxytocin-related gene genotypes, dopamine-related genotypes, and sex was found for the oxytocin receptor gene (OXTR)rs1042778 and the Catechol-O-Methyltransferase gene (COMT) rs4680 genotypes (p = 0.02) and for OXTR rs2254298 and the dopamine D2 receptor gene (DRD2) rs1800497 genotypes (p = 0.01). Further sex-stratified analyses revealed that the interaction between OXTR rs1042778 and COMT rs4680 genotypes was associated with neighborhood trust among men (p = 0.0007). Also, the interaction between OXTR rs2254298 and DRD2 rs1800497 genotypes was associated with institutional trust among men (p = 0.005). Post-hoc analyses found that men with OXTR rs1042778 TG/TT and COMT rs4680 GG genotypes reported higher neighborhood trust than those with GG + AG/AA (B = 13.49, SE = 4.68, p = 0.02), TG/TT + AG/AA (B = 23.00, SE = 5.99, p = 0.001), and GG + GG (B = 18.53, SE = 5.25, p = 0.003). Similarly, men with OXTR rs2254298 AG/AA and DRD2 rs1800497 CC genotypes showed higher institutional trust than those with AG/AA + TT/TC (B = 15.67, SE = 5.30, p = 0.02). We could not find any interacting associations among women. While we note that our sample size and candidate gene approach have a potential risk of chance findings, our study provides an important foundation toward further exploration of sex-specific epistatic interaction effects of oxytocin- and dopamine-related genes on trust, indicating the importance of both systems in trust formation.

Contrasting Effects of Oxytocin on MK801-Induced Social and Non-Social Behavior Impairment and Hyperactivity in a Genetic Rat Model of Schizophrenia-Linked Features.

Social withdrawal in rodents is a measure of asociality, an important negative symptom of schizophrenia. The Roman high- (RHA) and low-avoidance (RLA) rat strains have been reported to exhibit differential profiles in schizophrenia-relevant behavioral phenotypes. This investigation was focused on the study of social and non-social behavior of these two rat strains following acute administration of dizocilpine (MK801, an NMDA receptor antagonist), a pharmacological model of schizophrenia-like features used to produce asociality and hyperactivity. Also, since oxytocin (OXT) has been proposed as a natural antipsychotic and a potential adjunctive therapy for social deficits in schizophrenia, we have evaluated the effects of OXT administration and its ability to reverse the MK801-impairing effects on social and non-social behavior and MK801-induced hyperactivity. MK801 administration produced hyperlocomotion and a decrease in social and non-social behavior in both rat strains, but these drug effects were clearly more marked in RHA rats. OXT (0.04 mg/kg and 0.2 mg/kg) attenuated MK801-induced hyperlocomotion in both rat strains, although this effect was more marked in RHA rats. The MK801-decreasing effect on exploration of the "social hole" was moderately but significantly attenuated only in RLA rats. This study is the first to demonstrate the differential effects of OXT on MK801-induced impairments in the two Roman rat strains, providing some support for the potential therapeutic effects of OXT against schizophrenia-like symptoms, including both a positive-like symptom (i.e., MK801-induced hyperlocomotion) and a negative-like symptom (i.e., MK801 decrease in social behavior), while highlighting the importance of the genetic background (i.e., the rat strain) in influencing the effects of both MK801 and oxytocin.

Oxytocin decreases alcohol self-administration in male baboons

The neurohormone oxytocin (OT) has been proposed as a treatment for alcohol and nicotine use disorders. The aim of the present study was to examine whether intravenous (IV) OT decreases alcohol oral self-administration and consumption in nonhuman primates under a 6-h alcohol access procedure as well as alcohol and nicotine (IV) self-administration under 6-h concurrent access conditions. The subjects were five male baboons (Papio anubis) that self-administered oral alcohol (4% w/v) during 6-h sessions under a fixed ratio 3 (FR3) schedule per drink. Baseline levels of alcohol self-administration were established and then OT treatment was initiated. A single dose of OT (20, 40, 80, 120 IU, IV) or its vehicle (saline) was administered before and again in the middle of the 6-h drinking session for 5 consecutive days (total oxytocin dose of 40, 80, 160, 240 IU/day). After each 5-day treatment, baseline levels of alcohol self-administration were reestablished before the next 5-day OT treatment. In addition, the effect of OT on concurrent alcohol and IV nicotine self-administration was explored in 3 of the baboons where alcohol and nicotine were concurrently available during the 6-hr session each under an FR3 schedule for each drug. Establishment of baseline self-administration and 5-day OT treatments were completed as in the alcohol only study. There was a significant overall reduction in alcohol consumption with OT compared to placebo. On post-hoc analysis, after correcting for multiple comparisons, the 40 and 80 IU doses of OT significantly reduced alcohol consumption compared with vehicle, and consumption did not vary significantly within each 5-day treatment period. OT, qualitatively, also reduced the coadministration of both alcohol and nicotine in each baboon for at least one of the OT doses administered. These results underscore the therapeutic potential of oxytocin as a treatment of alcohol use disorder and possibly, co-use of nicotine.

Oxytocin modulation of explicit pandemic stigma in men with varying social anxiety levels

ObjectiveStigma can create divisions within societies, hindering social cohesion and cooperation. Notably, it has significant public health implications, especially during infectious disease outbreaks like COVID-19. However, little is known about the neural and molecular basis of disease-related stigma and their association with individual differences. MethodsTo address this gap, we performed a double-blind, placebo-controlled, within-subject design study with 70 males, to investigate the effect of intranasal oxytocin (OT) administration on the explicit and implicit processing of disease-related stigma (i.e., COVID-19 stigma). After self-administrated 24 IU of OT or placebo, participants completed a stigma evaluation task and an Implicit Association Test (IAT) to assess the explicit and implicit processes of stigma evaluation, respectively. ResultsThe results showed that oxytocin amplified the differences between participants with high and low social anxiety in explicit COVID-19 stigma, with a higher inclination to attribute the stigmatized status of the stigmatized targets (i.e., COVID-19 related group) to personal causes in high social anxiety individuals, but reduced blame towards the stigmatized targets in low social anxiety individuals under oxytocin compared to placebo treatment. Furthermore, oxytocin strengthened the connections between responsibility attribution and the other processes (i.e., emotional, approach motivation, social deviance). While no modulation of oxytocin on implicit stigma emerged, oxytocin did modulate the associations between specific dimensions of explicit stigma (i.e., social deviance and approach motivation) and implicit stigma. ConclusionIn conclusion, these findings demonstrated that intranasal oxytocin administration could temporally impact the explicit cognitive judgment in disease-related stigma but not the implicit aspect; furthermore, it modulated in distinct ways in individuals with different levels of social anxiety. These findings highlight the trait-dependent oxytocin modulation on disease-related stigma, implying that oxytocin is partly involved in the endocrine system of disease-related stigma. By unraveling the molecular basis of stigma and its association with individual traits, such as social anxiety, we can tailor interventions to meet specific needs of different individuals in the future.

The oxytocinergic system and racial ingroup bias in empathic neural activity

Studies have indicated that the human brain exhibits a more robust neural empathic response towards individuals of the same racial ingroup than those of the outgroup. However, the impact of the oxytocinergic system on the dynamic connectivity between brain regions involved in racial ingroup bias in empathy (RIBE) and its implications for real-life social interaction intention remains unclear. To address this gap, we employed functional magnetic resonance imaging (fMRI) to investigate RIBE-modulated neural activities and the influence of the oxytocinergic system at both neural and behavioral levels. Participants homozygous for the A/A and G/G genotypes of the oxytocin receptor gene (OXTR) rs53576 polymorphism underwent scanning while making judgments about painful versus non-painful stimuli in same-race versus other-race scenarios following either oxytocin (OT) or placebo treatment. The results revealed greater activity in the anterior cingulate cortex (ACC) and anterior insula (AI) in response to same-race compared to other-race models in the G/G group but not in the A/A group. RIBE also modulated the connections between bilateral AI and the ACC, and the effect of OT on this modulatory effect was moderated by genotype rs53576 and interpersonal trust. Moreover, more extensive changes in AI-ACC connections were associated with higher levels of revenge intention in the low interpersonal trust group. Overall, our findings suggest a pivotal role of the oxytocinergic system in the RIBE-modulated neural activities and revenge intention in human interactions with the modulatory effect of interpersonal trust.This article is part of the Special Issue on “Empathic Pain”.