Plasma Oxytocin Research Articles

Targeting the Oxytocin System to Ameliorate Early Life Depressive-Like Behaviors in Maternally-Separated Rats.

Oxytocin (OXT) -"the love hormone"- has been involved in the anti-depressant activity of some selective serotonin reuptake inhibitors (SSRIs). The exact mechanism underlying the OXT pathway in depression is not fully clear. This study aimed to investigate the effect of OXT analogue, carbetocin (CBT) and the SSRI, escitalopram (ESCIT) on depressive-like behaviors following maternal separation (MS). It is worthy to mention that intranasal CBT has been approved by U.S. Food and Drug Administration (FDA) for Prader-Willi syndrome. Adolescent Wistar albino maternally-separated rats were given CBT, (100 µg/animal/d via inhalation route), and, ESCIT, (20 mg kg-1, per os ( p.o.)) either alone or in combination for 7 d. Repeated 3-h MS demonstrated increased immobility time in forced swim test (FST) and decreased locomotor activity in open field test. MS elevated plasma level of adrenocortico-trophic hormone (ACTH) but notably reduced plasma OXT, with no effect on hippocampal OXT-R expression. Following MS, hippocampal contents of 5-hydroxytryptamine receptors (5HT1A-R), serotonin transporter (SERT) were increased. CBT and ESCIT corrected the behavioral dysfunction in FST and suppressed the high levels of ACTH. Additionally, both treatments boosted OXT level, reduced 5HT1A-R and normalized SERT contents, which reflects increased availability of serotonin. Finally, CBT markedly ameliorated the histopathological damage induced by MS and suppressed the increased glial fibrillary acidic protein. CBT and ESCIT manage depressive-like behavior by positively affecting serotonergic and oxytocinergic systems. Targeting OXT system -using CBT- ameliorated depressive like behaviors induced by maternal separation most probably via enhancing OXT plasma levels, attenuating hormonal ACTH and restoring the expression of hippocampal oxytocin and serotonin mechanisms.

The Methylation of Clock Genes in Perinatal Depression: Which Role for Oxytocin?

Background: Perinatal Depression (PD) is a widespread disabling condition that is hypothesized to be associated with abnormalities in circadian rhythms and neuropeptide release including oxytocin (OXT).Methods: Fourty-four pregnant women (28 with PD, and 16 controls) were evaluated through the Edinburgh Postnatal Depression Scale (EPDS), the State/Trait Anxiety Inventory Form Y (STAI-Y), and the Prenatal Attachment Inventory (PAI). A blood sample was collected from all participants, and OXT plasma levels, DNA methylation of clock genes, as well as of FOXp3 and HERV-W were measured. Linear regression analyses were performed to assess the effect of oxytocin on the methylation of selected genes. Continuous ordinal regression models was further applied to see if the score of rating scales was associated to gene methylation, adjusting for oxytocin-methylation interaction.Results: OXT plasma levels were positively associated with CRY1 methylation. Women with higher OXT plasma levels showed an association between higher degree of CRY2 methylation (thus, reduced expression) and lower EPDS (OR = 0.21; P = 0.043) and STAI-S scores (OR = 6.96; P = 0.019). Finally, with high OXT levels, hypermethylation of CRY1 was associated to higher scores on the PAI (OR = 2.74; P = 0.029) while higher methylation of HERV-W related to lower PAI scores (OR = 0.273; P = 0.019).Conclusion: Our results suggest a possible protective role played by oxytocin in the development of PD by promoting a favorable methylation profile characterized by reduced expression of CRY1 and CRY2. Moreover, oxytocin strengthens the association between maternal prenatal attachment with a favorable pattern of methylation of clock genes and HERV-W, which is essential for pregnancy outcomes.

Canine parturition: what is known about the hormonal setting?

Parturition is a challenging physiological process with perfect timing dictated by the events leading to the end of pregnancy in the female, and by the maturation of the fetus(es). The process of parturition remains an intricate interaction of hormones in a fine-tuned timing that remains to be better elucidated in the dog. In the dog pregnancy is maintained by the progesterone production by the corpora lutea, in which some hormones play a luteotrophic action. At term of pregnancy, the pre-parturient luteolytic cascade is the most apparent event, characterized by a rapid decline in plasma progesterone concentrations and useful in predicting the onset of spontaneous parturition. In contrast, cortisol plasma concentrations measurement showed high variability and suggested to be related to the stress condition instead of the onset of parturition. Both prostaglandin F2α and E2 concur in the process of parturition in the dog. The measurement of oxytocin plasma concentrations, also very variable, is implicated in uterine contractions. The measurement of plasma oxytocin concentrations showed to be useful to distinguish between normal and disturbed parturition, allowing the prompt recognition of dystocia and the immediate obstetrical intervention. In contrast to other species, no significant roles of estrogens for the initiating of parturition were demonstrated. Relaxin, the main pregnancy hormonal marker in the dog, beside an endocrine action, is also supposed to play a paracrine/autocrine role at the utero-placental unit and to support the maintenance of high plasma progesterone concentrations through a luteotrophic action, concurring to the main action of prolactin. Although important information has been provided, some aspects in the understanding the hormonal interactions and action timing implications in the process of parturition in the dog remains to be better investigated and represent intriguing topic for basic knowledge and applied research.

An improved sample extraction method reveals that plasma receptor for advanced glycation end-products (RAGE) modulates circulating free oxytocin in mice

The receptor for advanced glycation end-products (RAGE) binds oxytocin (OT) and transports it from the blood to the brain. As RAGE’s OT-binding capacity was lost in RAGE knockout (KO) mice, we predicted that circulating concentrations of unbound (free) OT should be elevated compared to wild-type (WT) mice. However, this hypothesis has not yet been investigated. Unfortunately, the evaluation of the dynamics of circulating free and bound plasma OT is unclear in immunoassays, in part because of interference from plasma proteins. A radioimmunoassay (RIA) is considered the gold standard method for overcoming this issue, but is more challenging to implement; thus, commercially available enzyme-linked immunosorbent assays (ELISAs) are more commonly used. Here, we developed a pre-treatment method to remove the interference-causing components from plasma before performing ELISA. The acetonitrile protein precipitation (PPT) approach was reliable, with fewer steps needed to measure free OT concentrations than by solid-phase extraction of plasma samples. PPT-extracted plasma samples yielded higher concentrations of OT in RAGE KO mice than in WT mice using ELISA. After peripheral OT injection, free OT plasma levels spiked immediately then rapidly declined in WT mice, but remained high in KO mice. These results suggest that plasma samples with PPT pre-treatment appear to be superior and that circulating soluble RAGE can most likely serve as a buffer for plasma OT, which indicates a novel physiological function of RAGE.

Oxytocin in pig seminal plasma is positively related with in vivo fertility of inseminated sows

BackgroundIdentification of relevant in vivo biomarkers for fertility remains a challenge for the livestock industry. Concentrations of the small peptide hormone oxytocin (OXT), involved in male reproductive function and present in the seminal plasma (SP) of several species could be a robust one. This study characterized concentrations of SP-OXT in ejaculates from boars used in artificial insemination (AI) programs aiming to evaluate its relationship with sperm quality variables and in vivo fertility of their liquid-stored AI-semen. Seminal OXT concentrations (ng/mL) were measured in 169 ejaculates from 61 boars of the Duroc, Pietrain, Landrace and Large White breeds using a direct competitive immunoassay test based on AlphaLISA® technology. Ejaculate (ejaculate volume, sperm concentration, total sperm count) and sperm parameters (motility, viability, intracellular generation of reactive oxygen species, plasma membrane fluidity) were assessed at 0 h and 72 h in AI-semen samples stored at 17 °C. In vivo fertility included only 18 Large White and Landrace boars whose AI-semen was used to inseminated > 100 sows and evaluated both farrowing rate and litter size of 3,167 sows.ResultsThe results showed that SP-OXT differed between boars and between ejaculates within boar (P < 0.05) but not between breeds (Duroc, Pietrain, Landrace and Large White). Ejaculates with higher SP-OXT concentration/mL (hierarchically grouped; P < 0.001) had larger volume and came from younger boars (P < 0.05). Ejaculates of boars showing positive farrowing rate deviation exhibited higher (P < 0.05) SP-OXT concentration/mL than those with negative farrowing rate deviation.ConclusionThe SP concentrations of OXT are boar, ejaculate and age dependent, and positively related with ejaculate volume and farrowing rates of liquid-stored semen AI-doses.

Oxytocin levels in response to pituitary provocation tests in healthy volunteers.

Oxytocin, secreted into circulation through the posterior pituitary, regulates lactation, weight, and socio-behavioral functioning. Oxytocin deficiency has been suggested in patients with hypopituitarism; however, diagnostic testing for oxytocin deficiency has not been developed. The aim of this study was to investigate known pituitary provocation tests to stimulate plasma oxytocin. Sixty-five healthy volunteers underwent either the hypertonic saline or arginine infusion test, known to stimulate copeptin, or the oral macimorelin test, known to stimulate growth hormone. Plasma oxytocin was measured before and once plasma sodium level ≥ 150 mmol/L for the hypertonic saline, after 60 min for the arginine infusion, and after 45 min for the oral macimorelin test (expected peak of copeptin and growth hormone levels, respectively). Primary outcome was a change from basal to stimulated oxytocin levels using paired t-tests. As expected, copeptin increased in response to hypertonic saline and arginine infusion (P < 0.001), and growth hormone increased to oral macimorelin (P < 0.001). Oxytocin increased in response to hypertonic saline infusion from 0.4 (0.2) to 0.6 pg/mL (0.3) (P = 0.003) but with a high variance. There was no change to arginine infusion (P = 0.4), and a trend to lower stimulated levels to oral macimorelin (P = 0.05). Neither the arginine infusion nor the oral macimorelin test stimulates plasma oxytocin levels, whereas there was an increase with high variance upon hypertonic saline infusion. As a predictable rise in most participants is required for a reliable pituitary provocation test, none of the investigated pituitary provocation tests can be recommended diagnostically to identify patients with an oxytocin deficiency.

Does plasma oxytocin mediate stress reduction after compassion-based mental training?

Does plasma oxytocin mediate stress reduction after compassion-based mental training?

Sequential Social Exclusion in a Novel Cyberball Paradigm Leads to Reduced Behavioral Repair and Plasma Oxytocin in Borderline Personality Disorder.

Patients with borderline personality disorder (BPD) show interpersonal deficits, and altered emotional and oxytocin (OT) responses to social exclusion (Cyberball). In order to extend previous findings, this study applies a novel Cyberball variant. Nineteen BPD patients and 56 healthy controls (HC) played Cyberball for 2 minutes of inclusion, 5 minutes of partial exclusion by one of two co-players, and 2 minutes total exclusion by both. Plasma OT levels at baseline and after 7, 9, 15, and 40 minutes were measured with radioimmunoassay. BPD patients showed a greater aversive reaction and a trend for greater OT reduction after social exclusion than HC. BPD patients also tended to play less frequently with the excluder. Though limited by our sample size, we partially replicate previous findings. Our preliminary behavioral data support the notion of an altered OT regulation and reduced capacity for social cooperation in BPD.

Childhood Trauma and Aggression in Persons Convicted for Homicide: An Exploratory Study Examines the Role of Plasma Oxytocin.

Evidence has demonstrated the association between childhood trauma and criminality in adulthood, however, less is known about how best to explain the route from childhood trauma to adulthood aggression. Results from both human and animal studies have generated the hypothesis that dysfunction of the oxytocinergic system may correlate with pathological aggression. The current study represents a first exploratory examination to investigate the trajectory from childhood trauma to aggression, specifically, plasma oxytocin's role in this association. We assessed the childhood trauma experiences in a total of 108 participants, including 33 persons convicted for homicide and 75 non-offending healthy participants, using the Childhood Trauma Questionnaire, with in-depth clarification interviews for cross-validation. All participants were checked for aggression using the Modified Overt Aggression Scale and their plasma oxytocin levels were obtained. Results indicated that persons convicted for homicide had higher childhood trauma scores and lower plasma oxytocin levels than healthy controls. The plasma oxytocin levels were inversely correlated with childhood trauma in all participants. Further mediation models were constructed to explore these associations, in the best-fit model, the relationship between childhood trauma and aggression is mediated by plasma oxytocin levels in persons convicted for homicide. In conclusion, the association between childhood trauma and aggression of persons convicted for homicide is mediated by their plasma oxytocin levels. With leading to further theoretical consideration in the causality on how best to explain the interaction between childhood trauma and aggression, the current study may assist in developing further research and preventive strategies for aggression, particularly the importance of early identification of childhood trauma.

Brief communication: Plasma cortisol concentration is affected by lactation, but not intra-nasal oxytocin treatment, in beef cows.

In mammals, including sheep and mice, lactation attenuates the hypothalamo-pituitary-adrenal axis and plasma cortisol concentration. Oxytocin, one neuropeptide present in the blood during lactation, may contribute to such stress attenuation. Providing oxytocin intra-nasally increases plasma oxytocin concentration in cattle and can be used in non-lactating cows to mirror plasma oxytocin concentration of lactating cows. Therefore, our hypothesis was that there would be no difference in plasma cortisol between non-lactating beef cows intra-nasally administered oxytocin and lactating beef cows intra-nasally treated with saline. Twenty Bos taurus cows were randomly allocated by lactational status to one of four treatments, in a 2×2 factorial arrangement: 1) Non-lactating, saline (NL-S; n = 5); 2) Non-lactating, oxytocin (NL-OXT; n = 5); 3) Lactating, saline (L-S; n = 5); and 4) Lactating, oxytocin (L-OXT; n = 5). Two hours pre-treatment, cows were catheterized, moved to their appropriate chute and baseline blood samples were collected at -60, -45, -30, and 0 minutes before treatments were administered. Directly following the 0-minute sample, cows were administered their intra-nasal treatment via a mucosal atomization device. Subsequently, blood was collected at 2, 4, 6, 8, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, and 120 minutes. Non-lactating cows had greater (P = 0.02) plasma cortisol concentration compared with lactating cows. There was no lactation by treatment interactions for either plasma cortisol (P = 0.55) or oxytocin (P = 0.89) concentration. Although a treatment by time interaction was identified for oxytocin (P < 0.0001), there was no main effect of lactation on plasma oxytocin concentration (P = 0.34). Similar oxytocin and dissimilar cortisol concentration in lactating and non-lactating cows indicate that oxytocin alone cannot be responsible for reduced plasma cortisol in lactating ruminants. Further investigations are needed to elucidate alternative mechanisms that may be involved in the stress hypo-responsive condition of lactating mammals.

Specificity of plasma oxytocin immunoassays: A comparison of commercial assays and sample preparation techniques using oxytocin knockout and wildtype mice

Oxytocin has garnered much interest due to its role in affective states, social behaviors, and diverse physiological functions. However, approaches for measuring endogenous oxytocin concentrations have generated considerable controversy and debate. Common procedures for measuring oxytocin often produce uncorrelated results, and the detected concentrations frequently vary across two orders of magnitude. These findings have led some researchers to argue that immunoassays of plasma oxytocin may be unreliable and nonspecific, particularly when samples are not first processed using an extraction procedure. Here, we assess the specificity of oxytocin immunoassays using plasma samples from wildtype (WT) and oxytocin knockout (KO) mice. Plasma samples from both genotypes were measured using immunoassay and were measured with or without a solid-phase extraction. Using a commercially available kit from Arbor Assays, we demonstrate that both techniques generate a clear contrast between genotypes, with wildtype samples containing high concentrations of oxytocin (unextracted mean = 468 pg/ml; extracted mean = 381 pg/ml), while knockout samples measured below the lower limit of detection. Analytical validations demonstrated good parallelism and spike recovery for both methods. Furthermore, the same wildtype samples measured with both procedures were highly correlated (r = 0.95), although unextracted samples measured at significantly higher concentrations (p = 2.0 ×10−7, Cohen’s d = 2.65). To test the generalizability of these results across immunoassay kits, we performed additional assays with kits from Cayman Chemical and Enzo Life Sciences. The Cayman Chemical kit produced results similar to Arbor Assays with a clean signal differentiating WT and KO plasma, both with and without an extraction step. The Enzo kit also differentiated the genotypes, with correlation between extracted and unextracted samples, but was considerably more susceptible to interference without the extraction, as evidenced by false positive signal in KO plasma samples. The extent to which these results generalize to other species remains unknown and challenging to assess.

Role of the 5-HT2A Receptor in Acute Effects of LSD on Empathy and Circulating Oxytocin.

The psychedelic lysergic acid diethylamide (LSD) has experienced a revival in research, including clinical trials that evaluate LSD-assisted psychotherapy. LSD induces perceptual alterations and influences emotion processing in ways that may support psychotherapy. Here, we investigated the effects of LSD on emotional empathy and mediating role of the serotonin 5-hydroxytryptamine-2A (5-HT2A) receptor by administering 25, 50, 100, and 200 µg LSD alone and 200 µg LSD combined with pretreatment with the 5-HT2A receptor antagonist ketanserin (40 mg) using a placebo-controlled, double-blind, random-order, crossover design in 16 healthy subjects. The Multifaceted Empathy Test (MET) was used to assess the effects of LSD on emotional empathy. Plasma oxytocin levels were also measured. LSD dose-dependently increased implicit and explicit emotional empathy, with the highest 200 µg LSD dose having a significant effect compared with placebo. The 200 µg dose of LSD also moderately increased plasma oxytocin levels compared with placebo. Ketanserin reduced the LSD-induced elevations of oxytocin but not the LSD-induced increases in emotional empathy. These findings confirm that LSD enhances empathy, and this effect may be partially independent of its primary action on 5-HT2A receptors to induce subjective psychedelic effects. In contrast, LSD-induced oxytocin release may depend on 5-HT2A receptor stimulation, which is consistent with the psychedelic effect of LSD. Further studies are needed to investigate whether LSD may also enhance empathy and potentially produce therapeutic effects in patients who have deficits in empathy and impairments in social functioning.

Decreased Plasma Oxytocin Levels in Patients With PTSD.

IntroductionAlthough the pathophysiology of post-traumatic stress disorder (PTSD) is still unclear, growing preclinical evidences suggest that oxytocin (OT), a pleiotropic hormone, is possibly involved. However, direct studies on OT levels or clinical trials with this exogenous hormone in patients with PTSD led to inconsistent findings. Therefore, the aim of the present study was at exploring and comparing the plasma OT levels in a group of patients with PTSD and matched healthy subjects as the control group.Materials and MethodsTwenty-six outpatients (13 men, 13 women, mean age: 40.3 ± 11.5 years) suffering from PTSD, according to the Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5), and 26 healthy subjects (13 men, 13 women, mean age: 43.8 ± 12.7 years) were included. The patients were assessed through the structured clinical interview for DSM-5 research version, patient edition (SCID-I/P), and the Impact for Event Scale revised (IES-R). All fasting subjects underwent three venous blood samples for the subsequent oxytocin radioimmunoassay. We used unpaired Student’s t-test to assess OT levels and the intergroup difference of demographic characteristics, while anxiety, avoidance, and hyperarousal scores were compared among groups adjusting for the effect of gender and age by means of analysis of covariance (ANCOVA). The correlations between different variables were investigated by Pearson’s method.ResultsThe most common traumatic events of patients with PTSD were the following: severe car accident, physical violence, sexual violence, sudden death of a loved one, and natural disaster. The IES total score was 55 ± 15. Student’s t-test revealed that the patients showed significantly lower OT levels (mean ± SD, pg/ml) than healthy control subjects (4.37 ± 1.61 vs 5.64 ± 2.17, p < 0.001). We detected no correlation between the IES total score, subscales, or single items and OT plasma levels. Again, no difference between men and women was detected in the patients’ group, while healthy control women showed higher OT levels than men.DiscussionOur study, while reporting the presence of decreased plasma OT levels in outpatients with PTSD of both sexes, as compared with healthy control subjects, would support the possible involvement of OT in the pathophysiology of PTSD. However, given the complexity of the clinical picture, future investigations are necessary to better deepen the role and level of OT in PTSD.

Prolonged efavirenz exposure reduces peripheral oxytocin and vasopressin comparable to known drugs of addiction in male Sprague Dawley rats.

IntroductionSeveral drugs of abuse (DOA) are capable of modulating neurohypophysial hormones, such as oxytocin (OT) and vasopressin (VP), potentially resulting in the development of psychological abnormalities, such as cognitive dysfunction, psychoses, and affective disorders. Efavirenz (EFV), widely used in Africa and globally to treat HIV, induces diverse neuropsychiatric side effects while its abuse has become a global concern. The actions of EFV may involve neurohypophysial system (NS) disruption like that of known DOA. This study investigated whether sub-chronic EFV exposure, at a previously-determined rewarding dose, alters peripheral OT and VP levels versus that of a control, ∆9-tetrahydrocannabinol (∆9-THC), methamphetamine (MA) and cocaine.Materials and methodsTo simulate the conditions under which reward-driven behavior had previously been established for EFV, male Sprague Dawley rats (n = 16/exposure) received intraperitoneal vehicle (control) or drug administration across an alternating sixteen-day dosing protocol. Control administration (saline/olive oil; 0.2 ml) occurred on odd-numbered and drug administration (EFV: 5 mg/kg, ∆9-THC: 0.75 mg/kg, MA: 1 mg/kg, or cocaine: 20 mg/kg) on even-numbered days followed by euthanasia, trunk blood collection and plasma extraction for neuropeptide assay. Effect of drug exposure on peripheral OT and VP levels was assessed versus controls and quantified using specific ELISA kits. Statistical significance was determined by Kruskal-Wallis ANOVA, with p < 0.05. Ethics approval: NWU-00291-17-A5.ResultsDelta-9-THC reduced OT and VP plasma levels (p < 0.0001, p = 0.0141; respectively), cocaine reduced plasma OT (p = 0.0023), while MA reduced plasma VP levels (p = 0.0001), all versus control. EFV reduced OT and VP plasma levels (p < 0.0001; OT and VP) versus control, and similar to ∆9-THC.ConclusionEFV markedly affects the NS in significantly reducing both plasma OT and VP equivalent to DOA. Importantly, EFV has distinct effects on peripheral OT and VP levels when assessed within the context of drug dependence. The data highlights a possible new mechanism underlying previously documented EFV-induced effects in rats, and whereby EFV may induce neuropsychiatric adverse effects clinically; also providing a deeper understanding of the suggested abuse-potential of EFV.

Early-life oxytocin attenuates the social deficits induced by caesarean-section delivery in the mouse

The oxytocin (OXT) system has been strongly implicated in the regulation of social behaviour and anxiety, potentially contributing to the aetiology of a wide range of neuropathologies. Birth by Caesarean-section (C-section) results in alterations in microbiota diversity in early-life, alterations in brain development and has recently been associated with long-term social and anxiety-like behaviour deficits. In this study, we assessed whether OXT intervention in the early postnatal period could reverse C-section-mediated effects on behaviour, and physiology in early life and adulthood. Following C-section or per vaginum birth, pups were administered with OXT (0.2 or 2 μg/20 μl; s.c.) or saline daily from postnatal days 1–5. We demonstrate that early postnatal OXT treatment has long-lasting effects reversing many of the effects of C-section on mouse behaviour and physiology. In early-life, high-dose OXT administration attenuated C-section-mediated maternal attachment impairments. In adulthood, low-dose OXT restored social memory deficits, some aspects of anxiety-like behaviour, and improved gastrointestinal transit. Furthermore, as a consequence of OXT intervention in early life, OXT plasma levels were increased in adulthood, and dysregulation of the immune response in C-section animals was attenuated by both doses of OXT treatment. These findings indicate that there is an early developmental window sensitive to manipulations of the OXT system that can prevent lifelong behavioural and physiological impairments associated with mode of birth.

Kamikihito, a traditional Japanese Kampo medicine, increases the secretion of oxytocin in rats with acute stress

Ethnopharmacological relevanceKamikihito (KKT) is a Kampo medicine that is prescribed in Japan for the treatment of anemia, insomnia and mental anxiety in Japan. However, its precise mechanism of action remains unclear. Aim of the studyThis study aimed to evaluate the possible antistress effect of KKT in rats with acute stress and the contribution of oxytocin to the process. Materials and methodsAcute immobilization stress (AIS; for 90 min) was used to assess the effect of KKT on acute stress. Male Wistar rats were orally treated with KKT. Parameters of stress were evaluated, and concentrations of oxytocin in plasma and cerebrospinal fluid (CSF) were measured. ResultsAIS-induced defecation and fecal weight were significantly decreased because of treatment with KKT. The plasma levels of stress-related hormones following AIS were investigated. The pre-administration of KKT significantly increased adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) levels following AIS. Conversely, there was no significant change in the plasma oxytocin level. Microdialysis and hydrophilic interaction liquid chromatography–tandem mass spectrometry (HILIC–MS/MS) were used to monitor the oxytocin secretion in CSF. Oxytocin level increased during AIS following the treatment of KKT. At 30 min after AIS, the level remained higher than before AIS. Furthermore, using an open field test, the locomotion (exploratory behavior) immediately after AIS was examined. The total traveled distance decreased after AIS; however, the decrease was significantly inhibited by the treatment of KKT. However, the effect of KKT was obstructed by the pre-administration of the oxytocin receptor antagonist. ConclusionsThese results suggest that KKT has antistress activity and increased oxytocin secretion may be a mechanism underlying this phenomenon.

A functional selective effect of oxytocin secreted under restraint stress in rats

Restraint stress (RS) is an unavoidable stress model that triggers activation of the autonomic nervous system, endocrine activity, and behavioral changes in rodents. Furthermore, RS induces secretion of oxytocin into the bloodstream, indicating a possible physiological role in the stress response in this model. The presence of oxytocin receptors in vessels and heart favors this possible idea. However, the role of oxytocin secreted in RS and effects on the cardiovascular system are still unclear. The aim of this study was to analyze the influence of oxytocin on cardiovascular effects during RS sessions. Rats were subjected to pharmacological (blockade of either oxytocin, vasopressin, or muscarinic receptors) or surgical (hypophysectomy or sinoaortic denervation) approaches to study the functional role of oxytocin and its receptor during RS. Plasma levels of oxytocin and vasopressin were measured after RS. RS increased arterial pressure, heart rate, and plasma oxytocin content, but not vasopressin. Treatment with atosiban (a Gi biased agonist) inhibited restraint-evoked tachycardia without affecting blood pressure. However, this effect was no longer observed after sinoaortic denervation, homatropine (M2 muscarinic antagonist) treatment or hypophysectomy, indicating that parasympathetic activation mediated by oxytocin secreted to the periphery is responsible for blocking the increase in tachycardic responses observed in the atosiban-treated group. Corroborating this, L-368,899 (oxytocin antagonist) treatment showed an opposite effect to atosiban, increasing tachycardic responses to restraint. Thus, this provides evidence that oxytocin secreted to the periphery attenuates tachycardic responses evoked by restraint via increased parasympathetic activity, promoting cardioprotection by reducing the stress-evoked heart rate increase.

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.

Neuroendocrine changes in the hypothalamic-neurohypophysial system in the Wistar audiogenic rat (WAR) strain submitted to audiogenic kindling.

The Wistar audiogenic rat (WAR) strain is used as an animal model of epilepsy, which when submitted to acute acoustic stimulus presents tonic-clonic seizures, mainly dependent on brainstem (mesencephalic) structures. However, when WARs are exposed to chronic acoustic stimuli (audiogenic kindling-AK), they usually present tonic-clonic seizures, followed by limbic seizures, after recruitment of forebrain structures such as the cortex, hippocampus and amygdala. Although some studies have reported that hypothalamic-hypophysis function is also altered in WAR through modulating vasopressin (AVP) and oxytocin (OXT) secretion, the role of these neuropeptides in epilepsy still is controversial. We analyzed the impact of AK and consequent activation of mesencephalic neurocircuits and the recruitment of forebrain limbic (LiR) sites on the hypothalamic-neurohypophysial system and expression of Avpr1a and Oxtr in these structures. At the end of the AK protocol, nine out of 18 WARs presented LiR. Increases in both plasma vasopressin and oxytocin levels were observed in WAR when compared to Wistar rats. These results were correlated with an increase in the expressions of heteronuclear (hn) and messenger (m) RNA for Oxt in the paraventricular nucleus (PVN) in WARs submitted to AK that presented LiR. In the paraventricular nucleus, the hnAvp and mAvp expressions increased in WARs with and without LiR, respectively. There were no significant differences in Avp and Oxt expression in supraoptic nuclei (SON). Also, there was a reduction in the Avpr1a expression in the central nucleus of the amygdala and frontal lobe in the WAR strain. In the inferior colliculus, Avpr1a expression was lower in WARs after AK, especially those without LiR. Our results indicate that both AK and LiR in WARs lead to changes in the hypothalamic-neurohypophysial system and its receptors, providing a new molecular basis to better understaind epilepsy.

Oxytocin Levels in Response to Pituitary Provocation Tests in Healthy Volunteers

Background: Oxytocin, secreted into the circulation through the posterior pituitary, regulates lactation, weight, and socio-behavioral functioning. Oxytocin deficiency has been suggested in patients with hypopituitarism, however, diagnostic testing for oxytocin deficiency has not been developed. Known stimuli used in the diagnosis of pituitary deficiencies - the hypertonic saline and arginine infusion tests stimulating copeptin levels, and the oral macimorelin test stimulating growth hormone levels - have also been shown to stimulate oxytocin secretion in animal models. We hypothesized that these provocation tests would stimulate plasma oxytocin levels in humans. Methods: Basal plasma oxytocin levels were measured for all three tests. Stimulated plasma oxytocin was measured once plasma sodium >150 mmol/l for the hypertonic saline and after 45 minutes for the arginine infusion and the oral macimorelin test, expected peak of copeptin and growth hormone levels, respectively. Primary outcome was change between basal and stimulated oxytocin levels using a paired t-test. Results: Median (IQR) age of all participants was 24 years (22, 28), 51% were female. As expected, copeptin increased in response to hypertonic saline from 4.0 pmol/L [3.3, 6.7] to 34.2 pmol/L [23.2, 45.4] (p-value <0.001) and in response to arginine infusion from 4.6 pmol/L [3.2, 6.2] to 8.3 pmol/L [6.4, 10.8] (p-value <0.001). Growth hormone increased in response to oral macimorelin from 1.6 ng/mL [0.3, 17.2] to 106.0 ng/mL [73.3, 127.2] (p-value <0.001). Oxytocin levels increased in response to hypertonic saline infusion from 0.3 pg/mL [0.3, 0.5] to 0.6 pg/mL [0.4, 0.7] (p-value 0.007), while there was no change in response to arginine infusion (basal 0.4 pg/mL [0.4, 0.6], stimulated 0.4 pg/mL [0.3, 0.6], p-value 0.6), nor to oral macimorelin (basal 38.7 pg/mL [31.1, 66.9], stimulated 34.2 pg/mL [31.2, 48.2], p-value 0.3). Conclusion: We found that hypertonic saline infusion results in doubling of oxytocin levels. Further research will be important to determine whether this test could be used diagnostically to identify patients with oxytocin deficiency. In contrast to animal data, arginine and macimorelin did not stimulate oxytocin.