Serum Oxytocin Concentrations Research Articles

Deschloroclozapine exhibits an exquisite agonistic effect at lower concentration compared to clozapine-N-oxide in hM3Dq expressing chemogenetically modified rats

IntroductionWithin the realm of chemogenetics, a particular form of agonists targeting designer receptors exclusively activated by designer drugs (DREADDs) has emerged. Deschloroclozapine (DCZ), a recently introduced DREADDs agonist, demonstrates remarkable potency in activating targeted neurons at a lower dosage compared to clozapine-N-oxide (CNO).MethodsWe conducted a comparative analysis of the effects of subcutaneously administered CNO (1 mg/kg) and DCZ (0.1 mg/kg) in our transgenic rats expressing hM3Dq and mCherry exclusively in oxytocin (OXT) neurons.Results and DiscussionNotably, DCZ exhibited a swift and robust elevation of serum OXT, surpassing the effects of CNO, with a significant increase in the area under the curve (AUC) up to 3 hours post-administration. Comprehensive assessment of brain neuronal activity, using Fos as an indicator, revealed comparable effects between CNO and DCZ. Additionally, in a neuropathic pain model, both CNO and DCZ increased the mechanical nociceptive and thermal thresholds; however, the DCZ-treated group exhibited a significantly accelerated onset of the effects, aligning harmoniously with the observed alterations in serum OXT concentration following DCZ administration. These findings emphasize the remarkable efficacy of DCZ in rats, suggesting its equivalent or potentially superior performance to CNO at considerably lower dosages, thus positioning it as a promising contender among DREADDs agonists.

Levels of leptin, irisin, oxytocin and insulin in obese and normal weight Iraqi young men

Introduction and Aim: Obesity is a serious, life-threatening health condition that is prevalent in Iraq and the world as a whole. Since Leptin, irisin, oxytocin and insulin are proposed to play main roles in energy expenditure, glucose homeostasis, regulating body weight, reducing obesity and improving life expectancy so the aim of this study was to evaluate the concentrations of these anti-obesity hormones plus insulin resistance Materials and Methods: The study was conducted on 100 obese young men with a mean age of 29.95 years and fifty normal weight young men with a mean age of 28.44. Results: In obese men, the mean leptin concentration was 24.08±9.91 ng/ml which was significantly higher than in normal weight men 5.48 ng/ml. Serum irisin levels in obese men and normal weight were 8.9 ng/ml, 2.4 ng/ml respectively, and it was significantly higher in obese group in comparison to the normal weight group. The mean serum oxytocin concentration was significantly lower in obese group 6.41pg/ml in comparison to normal weight 29.55 pg/ml. Serum insulin levels in obese and normal weight were 19.55±5.56 and 3.64 micro lU/ml respectively and it was significantly higher in obese men. The mean fasting blood glucose concentration in obese men was 98.67mg/dl and it was significantly higher than in normal weight 84±9.85 mg/ml. Insulin resistance (HOMA IR) was significantly higher in obese men 6.6 than in normal weight 0.68. Conclusion: Serum levels of leptin, irisin, insulin, and insulin resistance are higher in obese young men, while oxytocin levels were noticeably low. Our study also shows that obesity increases the likelihood of insulin resistance.

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

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

Developmental Changes in Hypothalamic and Serum Oxytocin Levels in Prenatally Normally Nourished and Undernourished Rats.

Changes in the activities of some metabolic factors have been suggested to increase the risk of conditions associated with the Developmental Origins of Health and Disease (DOHaD). We examined changes in oxytocin (OT), a metabolic factor, and OT receptor (OTR) mRNA levels throughout the developmental period in rats of intrauterine undernutrition. Pregnant rats were divided into two groups: a maternal normal nutrition (mNN) and maternal undernutrition (mUN) group. Serum OT concentrations and hypothalamic mRNA levels of OT and OTR were measured in both offspring at various postnatal stages. Both offspring showed significant increases in serum OT concentrations during the neonatal period, significant reductions around the pubertal period, and significant increases in adulthood. Hypothalamic OT mRNA expression levels gradually increased from the neonatal to pubertal period and decreased in adulthood in both offspring. In the pre-weaning period, hypothalamic OT mRNA expression levels were significantly lower in the mUN offspring than in the mNN offspring. In the mUN offspring, hypothalamic OTR mRNA expression levels transiently increased during the neonatal period, decreased around the pubertal period, and increased again in adulthood, whereas transient changes were not detected in mNN offspring. These changes could affect nutritional and metabolic regulation systems in later life and play a role in the mechanisms underlying DOHaD.

No Change in Serum Oxytocin Concentrations in Patients with Treatment-Resistant Schizophrenia

No Change in Serum Oxytocin Concentrations in Patients with Treatment-Resistant Schizophrenia

Serum oxytocin concentrations in current and recent suicide survivors are lower than in healthy controls

BackgroundSuicide and suicide attempts are dramatic events both for the individuals concerned and for their social circles. From a psychopathological perspective, suicidal behavior could be understood as a severe breakdown in relations with their social worlds. Oxytocin is a neuropeptide highly involved in the perception of facets of social relationship such as their quality feelings of belongingness, and mutual trust. Given this, we expected that serum oxytocin concentrations would be lower in current and recent suicide survivors than in healthy controls. MethodsA total of 48 participants (mean age: 27 years; 62.5% females) took part in the study. Of these, 16 (62.5% females) survived a suicide attempt 12–24 h ago; 16 (62.5% females) had made a suicide attempt about 12 weeks ago, and 16 (62.5% females) were healthy age- and gender-matched controls. Blood samples were taken in the morning to assess serum oxytocin concentrations. Participants also completed questionnaires covering sociodemographic information and a scale assessing suicidal ideation. ResultsCompared to healthy controls, suicide survivors had significantly lower serum oxytocin concentrations, but these levels did not differ between current and recent suicide survivors. Compared to healthy controls and recent suicide attempters, current suicide attempters recorded significantly higher scores on the Beck scale for suicidal ideation. Across the sample as a whole, higher scores for suicidal ideation were associated with lower serum oxytocin concentrations. Serum oxytocin concentrations and scores on the Beck scale for suicidal ideation did not differ between females and males. ConclusionsGiven that oxytocin is a neurobiological correlate of subjectively perceived quality of social interaction and social relationships, the results support the notion that suicide attempts are closely linked to suicide survivors' perceptions of the quality of their social lives. Speculatively, and based on the serum oxytocin concentrations, it also appears that 12 weeks after a suicide attempt, the survivor's perceived quality of social life has not significantly improved.

Low Serum Oxytocin Concentrations Are Associated with Painful Menstruation.

Oxytocin-dependent mechanisms are hypothesized to contribute to painful menses, but clinical trials of oxytocin antagonists for dysmenorrhea have had divergent outcomes. In contrast, broader studies have shown that increased systemic oxytocin concentrations are associated with increased pain tolerance and improved psychosocial function. We sought to confirm whether increased serum oxytocin concentrations are associated with menstrual pain and other psychosocial factors. Women with a history of primary dysmenorrhea (n = 19), secondary dysmenorrhea (n = 12), and healthy controls (n = 15) completed pain and psychosocial questionnaires, provided a medical history, and rated their pain during the first 48h of menses. Serum samples were collected during menses to measure oxytocin concentrations. Oxytocin was significantly lower in participants with a history of primary (704 ± 33pg/mL; p < 0.001) or secondary (711 ± 66pg/mL; p < 0.01) dysmenorrhea compared to healthy controls (967 ± 53pg/mL). Menstrual pain over the past 3months (r = -0.58; p < 0.001) and during the study visit (r = -0.45; p = 0.002) was negatively correlated with oxytocin concentrations. Pain catastrophizing (r = -0.39), pain behavior (r = -0.32), and pain interference (r = -0.31) were also negatively correlated with oxytocin levels (p's < 0.05). Oxytocin was not significantly correlated with psychosocial factors. Contrary to our hypothesis, women with a history of primary or secondary dysmenorrhea had lower oxytocin concentrations during menses when compared to healthy controls. Lower circulating oxytocin concentrations were also associated with worse menstrual pain and pain-related behavior. When considering the existing literature, low circulating oxytocin may be a sign of dysfunctional endogenous pain modulation.

Serum oxytocin levels are elevated in body dysmorphic disorder and related to severity of psychopathology

The neurobiological mechanisms underlying the pathophysiology of body dysmorphic disorder (BDD) are not well-understood. Oxytocin is a central nervous system peptide which regulates socioemotional functioning and may mediate physiologic processes in a range of psychiatric disorders, particularly those characterized by interpersonal dysfunction. Examining the role of oxytocin in the development and maintenance of BDD may elucidate new targets for intervention. The present study examined endogenous serum oxytocin levels in BDD. Given the prominent deficits in social functioning in BDD, we expected that BDD would be characterized by low basal serum oxytocin concentrations, relative to healthy controls, and that low oxytocin levels would be associated with BDD symptom severity as well as poor performance on measures of social cognition. Twenty individuals with BDD and 28 healthy controls completed a fasting blood draw consisting of frequent sampling every five minutes for one hour to measure pooled levels of oxytocin. Contrary to our hypotheses, people with BDD displayed higher concentrations of oxytocin, compared to their healthy control counterparts, and their oxytocin levels were positively correlated with BDD symptom severity. There were no associations between oxytocin levels and measures of social cognition. These findings suggest increased production of endogenous oxytocin in BDD. Prospective research is needed to determine whether this contributes to or is a consequence of BDD symptomatology.

Protocols using detomidine and oxytocin induce ex copula ejaculation in stallions

Tricyclic antidepressives, such as imipramine, indirectly induce ejaculation by increasing the noradrenaline concentration, which triggers an α-adrenergic response, whereas α-adrenergic agonists, such as xylazine and detomidine, directly trigger ejaculation by activating the α-1 adrenergic receptors. Furthermore, serum oxytocin concentrations in stallions increase drastically before ejaculation, but decline immediately thereafter, implicating the role of this hormone in emission. The objectives of the present study were to: 1) compare the efficiency of various protocols for inducing ex copula ejaculation in stallions, 2) evaluate the benefits of including oxytocin in the protocols, and 3) compare the semen characteristics of ex copula versus in copula ejaculates. Nine protocols were used to induce ex copula ejaculation using various combinations of xylazine (X; 0.66 mg/kg, iv); oxytocin (O; 20 IU, iv), imipramine (I; 3 mg/kg, orally), and detomidine (D; 0.02 mg/kg, iv). Imipramine was given 2 h prior to the administration of α-adrenergic agonist (detomidine or xylazine) and oxytocin. If ejaculation did not occur within 10 min after treatment with an α-adrenergic agonist, a half-dose of the same product was injected. Twelve sexually mature stallions (6–26 y) were used; 9 of 12 stallions responded to the treatment. Two stallions responded to X or XO, four stallions responded to IX and IXO, one stallion responded to DO, and five responded to IDO. Stallions that responded to detomidine did not respond to xylazine. No stallion ejaculated in response to D, ID, or IO. Erections and masturbation occurred only in imipramine-treated stallions. Sperm quality was similar among all the protocols and was not significantly different from those in in copula ejaculates collected with an artificial vagina. In a separate trial, none of these protocols induced ex copula ejaculation in 2–3 y old stallions. The side effects included sialorrhea after imipramine administration in all the stallions and sedation after administration of xylazine or detomidine. In conclusion, the new protocol, IDO, and the traditional protocol, IX, had similar results, with IDO being a useful alternative protocol in stallions for which IX was not effective. Therefore, attempts using both the protocols are encouraged, as stallions that ejaculated upon administration of detomidine did not ejaculate when xylazine was administered, whereas those that responded to xylazine did not respond to detomidine.

Oxytocin levels and sex differences in autism spectrum disorder with severe intellectual disabilities

There were few reports of oxytocin (OXT) concentrations of autism spectrum disorder (ASD) patients with severe intellectual disabilities. We measured serum OXT concentrations in 79 hospitalized patients with severe intellectual disabilities (16–60 years old, 50 males and 29 females, 54 ASD patients) and investigated the associations between serum OXT concentration, symptom scores, sex differences, and autism spectrum disorder. There were no significant effects of diagnosis, severity of intellectual disabilities, and total score of the Japanese version of the Aberrant Behavior Checklist (ABC-J), the Childhood Autism Rating Scale-Tokyo Version (CARS-TV), and the Japanese version of the Repetitive Behavior Scale-Revised (RBS-R). However, there were sex differences in the correlations between OXT concentrations and subscale scores in the ASD group. The male ASD group (n = 39) showed negative correlations between RBS-R Self-injurious and Sameness subscale scores and serum OXT concentrations. In the female ASD group(n = 15), CARS-TV Nonverbal communication subscale scores and RBS-R Compulsive subscale scores were seen to positively correlate with serum OXT concentrations. These findings suggest that OXT functions differ in males and females with severe intellectual disabilities and that OXT partly affects autism and related to some of the repetitive behaviors and nonverbal communication, in ASD patients with severe intellectual disabilities.

Evaluation of behavior and endocrinological changes after REM sleep deprivation-induced mania-like behavior in mice

The pressure to stay up longer in our modern society due to constant exposure to artificial light and interactive activities; furthermore, social and economic pressures impact human physiology and behavior. Rapid eye movement sleep deprivation (REMSD) alters most of the hormones, which may have adverse behavioral changes and other health consequences like mania and other psychiatric disorders. The exact role of REMSD-altered hormonal levels and the manner in which emerging consequences lead to mania-like behavior is poorly understood. Thus, we sought to verify the behavior and endocrinological changes after 48, 72, and 96 h of REMSD-induced mania-like behavior in mice. We performed modified multiple platform method of depriving the REM sleep for 48, 72 and 96 h, respectively, and one group maintained as a control. Motor assessment and aggressive behavior were determined by IR-Actimeter and Resident Intruder Test. Quantitative determination of serum thyroid hormones (TSH, T4, and T3), testosterone, corticosterone (CORT), prolactin (PRL), adrenocorticotropic hormone (ACTH), oxytocin (OT) and melatonin (MT) concentrations were determined by ELISA method. After respective hours of REMSD, the higher locomotion noticed among all REMSD mice and also showed higher aggressive behavior compared with control. Concentration of serum TSH and T4 was declined and elevated the T3, PRL, CORT, testosterone, ACTH, OT and MT levels in REMSD mice. These experiments showed that concentrations for the majority of the studied hormone and behavior were disrupted during REMSD. Our study indicated that REMSD results in mania-like behavior in mice and associated disruption to hormonal levels, although the exact mechanisms by which these take place remain to be determined.

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

In recent years more and more studies have revealed the effect of extraneous oxytocin on the social behavior of dogs. The distribution of administered oxytocin in different physiologically relevant compartments is important because this knowledge forms the basis for the timing of behavior tests after the administration. Most behavioral studies rely on the non-invasive intranasal application of oxytocin. The aim of this study was to determine the time course of intranasal administered oxytocin secretion into blood and urine and also establish a connection between intranasal received oxytocin and urinary cortisol in dogs. In our experiment, four dogs received three puffs, 12 IU intranasal oxytocin treatment, two dogs received three puffs intranasal placebo treatment. Blood and urine samples were collected immediately prior to the administration then regularly during 4 h. After nasal oxytocin application, the serum oxytocin concentration increased, reached a maximum 15 min after the treatment and then rapidly returned to baseline levels 45 min later. The peak urinary oxytocin concentration occurred between 45 and 60 min after administration and returned to baseline levels slowly. We found considerable differences among individuals in the secretion of oxytocin in both the serum and the urinary oxytocin concentration measurements. Our results confirm that intranasally administered oxytocin passes into the blood stream. The time course of intranasally administered oxytocin secretion is similar to the time course of intravenously administered oxytocin secretion, and the peak values are also similar in both the serum and the urinary oxytocin concentration measurements, although there are large individual differences.

Oxytocin receptor antagonist treatments alter levels of attachment to mothers and central dopamine activity in pre-weaning mandarin vole pups

Oxytocin (OT) is known to be important in mother-infant bonding. Although the relationship between OT and filial attachment behavior has been studied in a few mammalian species, the effects on infant social behavior have received little attention in monogamous species. The present study examined the effects of OT receptor antagonist (OTA) treatment on attachment behavior and central dopamine (DA) activity in male and female pre-weaning mandarin voles (Microtus mandarinus). Our data showed that OTA treatments decreased the attachment behavior of pups to mothers, measured using preference tests at postnatal day 14, 16, 18 and 20. OTA treatments reduced serum OT concentration in pre-weaning pups and decreased tyrosine hydroxylase (TH) levels in the ventral tegmental area (VTA), indicating a decrease in central DA activity. In male and female pups, OTA reduced DA levels, DA 1-type receptor (D1R) and DA 2-type receptor (D2R) protein expression in the nucleus accumbens (NAcc). Our results indicate that OTA treatment inhibits the attachment of pre-weaning pups to mothers. This inhibition is possibly associated with central DA activity and levels of two types of dopamine receptor in the NAcc.

Serum Oxytocin Concentration in Patients Receiving Electroconvulsive Therapy: An Exploratory Study and Review of Literature.

Neuroendocrine biomarkers have long been studied in the context of electroconvulsive therapy (ECT). We prospectively assessed serum oxytocin change and moderators thereof in an exploratory study of patients receiving ECT. Serum oxytocin concentrations were assessed immediately before and 1 to 3 minutes after the first ECT in 33 patients with schizophrenia (n = 14), other nonaffective psychosis (n = 6), mania (n = 10), and depression (n = 3) who received 6 to 7 bitemporal, brief-pulse ECTs. Change in serum oxytocin was assessed in the sample as a whole, and as a function of age, sex, diagnosis, and treatment response. The primary outcome was change in serum oxytocin in the overall sample. There was much variation across patients; oxytocin concentrations increased marginally by a mean (standard deviation) (M [SD]) of 6.4 (82.7) pg/mL (P = 0.43). The M (SD) change was -8.2 (85.0) pg/mL in patients with schizophrenia and other nonaffective psychoses (P = 0.84). There was no significant correlation between change in Brief Psychiatric Rating Scale scores and change in oxytocin concentrations in patients with schizophrenia, other nonaffective psychoses, and mania (ρ = 0.10, P = 0.61). Serum oxytocin rose in men, after ECT, and fell in women (P = 0.01). Change in serum oxytocin immediately after the first ECT in a course may not be a useful biomarker of ECT action. This is the first report on the subject in a sample comprising mostly patients with nonaffective psychosis and mania rather than depression. We discuss our findings in the light of previous research and offer general conclusions about the field.

Correlation of Oxytocin (OTR) and Estrogen Receptor (ER) mRNA in the Canine Placenta with the Detected Circulating Levels of Oxytocin and Estrogen during Pregnancy and Parturition

Placenta is considered an important endocrine organ during gestation, as well as can also serve as a target organ for sex steroids and pituitary hormones, mainly for the cascade of events that trigger parturition. In order to initiate studies on the canine placental endocrinology regarding estrogen and oxytocin, the present study verified the correlation among the Estrogen Receptor alpha (ERα) and Oxytocin Receptor (OTR) gene expression in the placenta tissue with the serum concentrations of their respective hormones (estrogen and oxytocin) during canine pregnancy and parturition. Real-time PCR was performed to quantify the levels of ERα mRNA and OTR mRNA in the placenta tissue of bitches (n=46) during Early (up to 20 days of gestation; n=11), Mid (20 to 40 days; n=12) and Late Pregnancy (40 to 60 days; n=12) and Parturition (first stage of labor; n=11). Serum samples were collected for the evaluation of estradiol and oxytocin (OT) concentrations by radioimmunoassay. Placental ERα mRNA expression showed a progressive decrease along gestation towards parturition. Placental ERα mRNA expression was significantly higher until 40 days of pregnancy in comparison to Parturition. Regarding OTR mRNA expression, no statistical differences among groups were verified. The Parturition Group presented higher estrogen concentrations in relation to Early and Mid Pregnancy Groups. Serum oxytocin concentrations were not different among pregnancy and parturition. During late pregnancy, a positive correlation was observed between placental ERα mRNA and oxytocin serum concentration. In conclusion, ERα mRNA in the canine placental tissue varies in a time-dependent manner, especially during the period of placentation and placental growth. Conversely, serum estrogen concentrations do not regulate directly the changes in OT receptors expression in the canine placenta.

Effect of Suckling Systems on Serum Oxytocin and Cortisol Concentrations and Behavior to a Novel Object in Beef Calves.

We investigated differences between effects of natural- and bucket-suckling methods on basal serum oxytocin (OT) and cortisol concentrations, and the effect of OT concentration on affiliative and investigative behavior of calves to a novel object. Ten Japanese Black calves, balanced with birth order, were allocated evenly to natural-suckling (NS) and bucket suckling (BS) groups. Blood samples were collected at the ages of 1 and 2 months (1 week after weaning) calves, and serum OT and cortisol concentrations were measured using enzyme-linked immunosorbent assay and enzymeimmunoassay tests, respectively. Each calf at the age of 2 months (2 weeks after weaning) was released into an open-field with a calf decoy, and its investigative and affiliative behaviors were recorded for 20 minutes. In 1-month-old calves, the basal serum OT concentration (25.5±4.9 [mean±standard deviation, pg/mL]) of NS was significantly higher than that of BS (16.9±6.7) (p<0.05), whereas the basal cortisol concentration (5.8±2.5 [mean±standard deviation, ng/mL]) of NS was significantly lower than that in BS (10.0±2.8) (p<0.05). Additionally, a negative correlation was noted between serum OT and cortisol concentrations in 1-month-old calves (p = 0.06). Further, the higher serum OT concentration the calves had at 1 month old, the more investigative the calves were at 2 months old but not affiliative in the open-field with a calf decoy. Thus, we concluded that the natural suckling method from a dam elevates the basal serum OT concentration in calves, and high serum OT concentrations induce investigative behavior and attenuate cortisol concentrations.

The influence of systemically administered oxytocin on the implant-bone interface area: an experimental study in the rabbit.

PURPOSEThe purpose of this study was to assess the effect of systemically administered oxytocin (OT) on the implant-bone interface by using histomorphometric analysis and the removal torque test.MATERIALS AND METHODSA total of 10 adult, New Zealand white, female rabbits were used in this experiment. We placed 2 implants (CSM; CSM Implant, Daegu, South Korea) in each distal femoral metaphysis on both the right and left sides; the implants on both sides were placed 10 mm apart. In each rabbit, 1 implant was prepared for histomorphometric analysis and the other 3 were prepared for the removal torque test (RT). The animals received intramuscular injections of either saline (control group; 0.15 M NaCl) or OT (experimental group; 200 µg/rabbit). The injections were initiated on Day 3 following the implant surgery and were continued for 4 subsequent weeks; the injections were administered twice per day (at a 12-h interval), for 2 days per week.RESULTSWhile no statistically significant difference was observed between the two groups (P=.787), the control group had stronger removal torque values. The serum OT concentration (ELISA value) was higher in the OT-treated group, although no statistically significant difference was found. Further, the histomorphometric parameter (bone-toimplant contact [BIC], inter-thread bone, and peri-implant bone) values were higher in the experimental group, but the differences were not significant.CONCLUSIONWe postulate that OT supplementation via intramuscular injection weakly contributes to the bone response at the implant-bone interface in rabbits. Therefore, higher concentrations or more frequent administration of OT may be required for a greater bone response to the implant. Further studies analyzing these aspects are needed.

Neonatal paternal deprivation impairs social recognition and alters levels of oxytocin and estrogen receptor α mRNA expression in the MeA and NAcc, and serum oxytocin in mandarin voles

Paternal care is necessary for the healthy development of social behavior in monogamous rodents and social recognition underpins social behavior in these animals. The effects of paternal care on the development of social recognition and underlying neuroendocrine mechanisms, especially the involvement of oxytocin and estrogen pathways, remain poorly understood. We investigated the effects of paternal deprivation (PD: father was removed from neonatal pups and mother alone raised the offspring) on social recognition in mandarin voles (Microtus mandarinus), a socially monogamous rodent. Paternal deprivation was found to inhibit the development of social recognition in female and male offspring according to a habituation–dishabituation paradigm. Paternal deprivation resulted in increased inactivity and reduced investigation during new encounters with other animals. Paternal deprivation reduced oxytocin receptor (OTR) and estrogen receptor α (ERα) mRNA expression in the medial amygdala and nucleus accumbens. Paternal deprivation reduced serum oxytocin (OT) concentration in females, but had no effect on males. Our results provide substantial evidence that paternal deprivation inhibits the development of social recognition in female and male mandarin voles and alters social behavior later in life. This is possibly the result of altered expression of central OTR and ERα and serum OT levels caused by paternal deprivation.

Individual difference in serum oxytocin concentrations of calves and the correlation with those in dams

We examined individual differences in serum oxytocin concentrations (OT) of calves, and assessed whether these differences were correlated with their dams' milk and serum OT. Eight Holstein (H), nine Japanese Shorthorn (JS), and six Japanese Black (JB) calves were examined. Blood was collected three times during the first month in H calves, while their dams' blood was collected three times prior to parturition. Milk was collected twice after parturition from H cows. Blood from JS and JB calves were collected at 1 and 4 months old, while of their dams only once before parturition. Serum OT in H calves at 7 days old was significantly correlated with that at 30 days. Serum OT of JS calves at 1 month old was significantly correlated to that at 4 months, while of JB calves was also positively correlated (r = 0.70). Serum OT of calves showed significant individual differences in each breed. Serum OT of calves was not correlated with the milk OT of dams, except for 3-day-old calves that fed on their dams' milk. We concluded that although serum OT differed among individuals, this difference was stable within each individual and not affected by the serum OT of the dams.

Neuroanatomical Evidence That Kisspeptin Directly Regulates Isotocin and Vasotocin Neurons

Neuropeptide kisspeptin has been suggested to be an essential central regulator of reproduction in response to changes in serum gonadal steroid concentrations. However, in spite of wide kisspeptin receptor distribution in the brain, especially in the preoptic area and hypothalamus, the research focus has mostly been confined to the kisspeptin regulation on GnRH neurons. Here, by using medaka whose kisspeptin (kiss1) neurons have been clearly demonstrated to be regulated by sex steroids, we analyzed the anatomical distribution of kisspeptin receptors Gpr54-1 and Gpr54-2. Because the both receptors were shown to be activated by kisspeptins (Kiss1 and Kiss2), we analyzed the anatomical distribution of the both receptors by in situ hybridization. They were mainly expressed in the ventral telencephalon, preoptic area, and hypothalamus, which have been suggested to be involved in homeostatic functions including reproduction. First, we found gpr54-2 mRNA expression in nucleus preopticus pars magnocellularis and demonstrated that vasotocin and isotocin (Vasopressin and Oxytocin ortholog, respectively) neurons express gpr54-2 by dual in situ hybridization. Given that kisspeptin administration increases serum oxytocin and vasopressin concentration in mammals, the present finding are likely to be vertebrate-wide phenomenon, although direct regulation has not yet been demonstrated in mammals. We then analyzed co-expression of kisspeptin receptors in three types of GnRH neurons. It was clearly demonstrated that gpr54-expressing cells were located adjacent to GnRH1 neurons, although they were not GnRH1 neurons themselves. In contrast, there was no gpr54-expressing cell in the vicinities of neuromodulatory GnRH2 or GnRH3 neurons. From these results, we suggest that medaka kisspeptin neurons directly regulate some behavioral and neuroendocrine functions via vasotocin/isotocin neurons, whereas they do not regulate hypophysiotropic GnRH1 neurons at least in a direct manner. Thus, direct kisspeptin regulation of GnRH1 neurons proposed in mammals may not be the universal feature of vertebrate kisspeptin system in general.