Increase In Oxytocin Concentrations Research Articles

Oxytocin in response to MDMA provocation test in patients with arginine vasopressin deficiency (central diabetes insipidus): a single-centre, case-control study with nested, randomised, double-blind, placebo-controlled crossover trial

Disruptions of the hypothalamic-pituitary axis can cause an arginine vasopressin deficiency, also known as central diabetes insipidus. Patients with this condition are at high risk of additional oxytocin deficiency owing to the close anatomical proximity of oxytocin-producing neurons; however, no conclusive evidence for such a deficiency has been reported. We aimed to use 3,4-methylenedioxymethamphetamine (MDMA, also known as ecstasy), a strong activator of the central oxytocinergic system, as a biochemical and psychoactive provocation test to investigate oxytocin deficiency in patients with arginine vasopressin deficiency (central diabetes insipidus). This single-centre, case-control study with nested, randomised, double-blind, placebo-controlled crossover trial included patients with arginine vasopressin deficiency (central diabetes insipidus) and healthy controls (matched 1:1 by age, sex, and BMI) and was conducted at the University Hospital Basel, Basel, Switzerland. We used block randomisation to assign participants to receive either a single oral dose of MDMA (100 mg) or placebo in the first experimental session; patients received the opposite treatment at the next session, with a wash-out period of at least 2 weeks between the two sessions. Participants and investigators assessing the outcomes were masked to assignment. Oxytocin concentrations were measured at 0, 90, 120, 150, 180, and 300 min after MDMA or placebo. The primary outcome was the area under the plasma oxytocin concentration curve (AUC) after drug intake. The AUC was compared between groups and conditions using a linear mixed-effects model. Subjective drug effects were assessed throughout the study using ten-point visual analogue scales. Acute adverse effects were assessed before and 360 min after drug intake using a 66-item list of complaints. This trial is registered with ClinicalTrials.gov, NCT04648137. Between Feb 1, 2021, and May 1, 2022, we recruited 15 patients with arginine vasopressin deficiency (central diabetes insipidus) and 15 healthy controls. All participants completed the study and were included in the analyses. In healthy controls, median plasma oxytocin concentration was 77 pg/mL (IQR 59-94) at baseline and increased by 659 pg/mL (355-914) in response to MDMA, resulting in an AUC of 102 095 pg/mL (41 782-129 565); in patients, baseline oxytocin concentration was 60 pg/mL (51-74) and only slightly increased by 66 pg/mL (16-94) in response to MDMA, resulting in an AUC of 6446 pg/mL (1291-11 577). The effect of MDMA on oxytocin was significantly different between groups: the AUC for oxytocin was 82% (95% CI 70-186) higher in healthy controls than in patients (difference 85 678 pg/mL [95% CI 63 356-108 000], p<0·0001). The increase in oxytocin in healthy controls was associated with typical strong subjective prosocial, empathic, and anxiolytic effects, whereas only minimal subjective effects were observed in patients, in agreement with the lack of increase in oxytocin concentrations. The most frequently reported adverse effects were fatigue (eight [53%] healthy controls and eight [53%] patients), lack of appetite (ten [67%] healthy controls and eight [53%] patients), lack of concentration (eight [53%] healthy controls and seven [47%] patients), and dry mouth (eight [53%] healthy controls and eight [53%] patients). In addition, two (13%) healthy controls and four (27%) patients developed transient mild hypokalaemia. These findings are highly suggestive of clinically meaningful oxytocin deficiency in patients with arginine vasopressin deficiency (central diabetes insipidus), laying the groundwork for a new hypothalamic-pituitary disease entity. Swiss National Science Foundation, Swiss Academy of Medical Sciences, and the G&J Bangerter-Rhyner Foundation.

Effects of Human–Dog Interactions on Salivary Oxytocin Concentrations and Heart Rate Variability: A Four-Condition Cross-Over Trial

ABSTRACTDog ownership is often advocated for its potential benefits to human health, with changes to oxytocin and autonomic nervous system (ANS) activity proposed as possible underlying mechanisms. The aims of the current study were to a) examine the effect of two common types of human–dog interactions (dog-walking and affiliative interactions) on salivary oxytocin concentrations and heart rate variability (HRV, an indicator of ANS activity), and b) investigate any putative moderating role for the strength of human–dog attachment on such responses. Twenty-nine dog owners completed a four-condition random-order cross-over trial: dog-walking (DW); walking without the dog (W); affiliative human–dog interaction (H-DI); and resting without the dog (C). Each condition was performed for approximately 15 minutes. Saliva and HRV samples were collected before and after each condition. Linear mixed models were used to analyze data, with the participant considered a random effect; condition, order of conditions, and condition duration as fixed effects. Oxytocin concentrations were not significantly different following any of the four conditions. HRV was significantly reduced following DW (mean change HF HRV = –0.37, 95% CI = –0.70, –0.04) and W (mean change HF HRV = –0.49, 95% CI = –0.81, –0.17). Considering moderation by the strength of the human–dog bond, pairwise comparisons revealed that, compared with W, DW elicited an increase in oxytocin concentrations (mean change 9.32 pg/mL, 95% CI = 6.52, 12.12) and HRV (mean change SDRR = 0.41, 95% CI = 0.19, 0.63) in owners with lower levels of attachment. These owners also displayed increased oxytocin concentrations following H-DI (mean change 3.90 pg/mL, 95% CI = 1.48, 6.32), compared with C. Overall, we did not find a consistent pattern for positive oxytocin or HRV responses to human–dog interactions. The strength of owner–dog attachment was found to have a moderating effect, suggesting that human–dog interactions may elicit greater physiological responses in low-attachment individuals.

Inhibition of nociceptive dural input to the trigeminocervical complex through oxytocinergic transmission

Migraine is a complex brain disorder that involves abnormal activation of the trigeminocervical complex (TCC). Since an increase of oxytocin concentration has been found in cerebrospinal fluid in migrainous patients and intranasal oxytocin seems to relieve migrainous pain, some studies suggest that the hypothalamic neuropeptide oxytocin may play a role in migraine pathophysiology. However, it remains unknown whether oxytocin can interact with the trigeminovascular system at TCC level. The present study was designed to test the above hypothesis in a well-established electrophysiological model of migraine. Using anesthetized rats, we evaluated the effect of oxytocin on TCC neuronal activity in response to dural nociceptive trigeminovascular activation. We found that spinal oxytocin significantly reduced TCC neuronal firing evoked by meningeal electrical stimulation. Furthermore, pretreatment with L-368,899 (a selective oxytocin receptor antagonist, OTR) abolished the oxytocin-induced inhibition of trigeminovascular neuronal responses. This study provides the first direct evidence that oxytocin, probably by OTR activation at TCC level inhibited dural nociceptive-evoked action potential in this complex. Thus, targeting OTR at TCC could represent a new avenue to treat migraine.

The effect of farrowing duration and parity on preovulatory follicular size and oxytocin release of sows at subsequent oestrus.

This study examined the extent to which prolonged farrowing and parity are associated with plasma oxytocin concentrations and follicular development of oestrous sows during subsequent insemination. A total of 30 sows were allocated to two groups based on farrowing duration: (i) SHORT (n=14): 159±29min, (ii) LONG (n=16): 533±190min. The sows were also divided into two parity classes: (i) YOUNG (n=14): parity 2.5±0.8, (ii) OLD (n=16): parity 6.4±2.3. After weaning, the ovaries were examined daily with transrectal ultrasound. On the second day of oestrus, blood samples were collected for oxytocin (OT) assay at -15, -10, -5, 0, +1, +2, +3, +4, +6, +8, +10, +15, +20, +25, +30, +40, +50 and +60min with a boar contact between 0 and +10min. Boar presence stimulated an increase in OT concentrations (p<.05). During boar presence, OT in the LONG group was higher than in the SHORT group (p<.01). The sows in the OLD group had a longer farrowing duration than in the YOUNG group (p<.05). OT levels and diameters of follicles were more relevant for parity than was the duration of farrowing. We therefore conclude that the OT levels and follicular development of oestrous sows are associated due to parity but difficult to be predicted from the duration of previous farrowing.

First experiences with neuropsychological effects of oxytocin administration in childhood-onset craniopharyngioma.

The hypothalamic hormone oxytocin plays a major role in regulation of behavior and body composition. Quality of survival is frequently impaired in childhood craniopharyngioma patients due to sequelae such as behavioral deficits and severe obesity caused by tumor or treatment-related hypothalamic lesions. In our pilot cross-sectional study, we analyzed emotion recognition abilities and oxytocin concentrations in saliva and urine before and after single nasal administration of 24 IU oxytocin in 10 craniopharyngioma patients. Four craniopharyngioma presented with grade I lesions (limited to anterior hypothalamic areas) and 6 craniopharyngioma with grade II lesions (involving mammillary bodies and posterior hypothalamic areas). Emotional tasks were assessed before and after administration of oxytocin using the Geneva multimodal emotion portrayals corpus and the Multidimensional Mood Questionnaire. All patients presented with detectable levels of oxytocin before administration. Nasal administration of oxytocin was well-tolerated and resulted in increased oxytocin concentrations in saliva and urine. After oxytocin administration, craniopharyngioma patients with postsurgical lesions limited to the anterior hypothalamus area showed improvements in emotional identifications compared to craniopharyngioma patients with lesions of anterior and posterior hypothalamic areas. Focusing on correct assignments to positive and negative emotion categories, craniopharyngioma patients improved assignment to negative emotions. Oxytocin might have positive effects on emotion perception in craniopharyngioma patients with specific lesions of the anterior hypothalamic area. Further studies on larger cohorts are warranted.

Commentary: Oxytocin-Gaze Positive Loop and the Coevolution of Human-Dog Bonds.

Commentary: Oxytocin-Gaze Positive Loop and the Coevolution of Human-Dog Bonds.

Social evolution. Oxytocin-gaze positive loop and the coevolution of human-dog bonds.

Human-like modes of communication, including mutual gaze, in dogs may have been acquired during domestication with humans. We show that gazing behavior from dogs, but not wolves, increased urinary oxytocin concentrations in owners, which consequently facilitated owners' affiliation and increased oxytocin concentration in dogs. Further, nasally administered oxytocin increased gazing behavior in dogs, which in turn increased urinary oxytocin concentrations in owners. These findings support the existence of an interspecies oxytocin-mediated positive loop facilitated and modulated by gazing, which may have supported the coevolution of human-dog bonding by engaging common modes of communicating social attachment.

Oxytocin in rat nucleus raphe magnus influences pain modulation

The main function of Nucleus raphe magnus (NRM) is mostly pain mediation. Our previous study has demonstrated that oxytocin (OXT) regulates antinociception through the central nervous system rather than the peripheral organs, and pain stimulation increases OXT concentration in the NRM. The experiment was designed to investigate OXT in the rat NRM effect on pain modulation. The results showed that 1) pain stimulation increased OXT concentration in NRM perfusion liquid; 2) Intra-NRM microinjection of OXT increased the pain threshold in a dose-dependent manner, whereas intra-NRM microinjection of OXT receptor antagonist, desGly-NH2, d(CH2)5[D-Tyr2, Thr-sup-4]OVT decreased the pain threshold; 3) NRM pre-treatment with OXT receptor antagonist completely attenuated the pain threshold increase induced by intra-NRM administration of OXT. The data suggested that OXT in NRM was involved in antinociception via OXT receptors.

Alpha-1-Adrenergic Receptor Blockade Modifies Insulin-Regulated Aminopeptidase (IRAP) Activity in Rat Prostate and Modulates Oxytocin Functions

Oxytocin (OT) is one of the important paracrine factors that prostate synthesizes. OT maintains its resting tone and stimulates its contractile activity. However, the involvement of OT in modulating cell proliferation of the prostate is being investigated. In fact, alterations in OT concentrations accompany both benign prostatic hyperplasia/hypertrophy and carcinoma of the prostate. The enzyme Insulin-regulated aminopeptidase (IRAP) is the main responsible of OT levels regulation through its catabolism. To date, the long-acting selective α(1)-adrenergic receptor antagonist doxazosin is widely used to the treatment of BPH. Thus, our aim was to analyze the effects of doxazosin on IRAP specific activity and its putative effects on prostate OT regulation and functions. Fifteen male Wistar rats were treated subcutaneously with 10 mg/Kg doxazosin during 15 days and fifteen controls were treated with the vehicle only. After the treatment period, prostate was removed to obtain soluble and membrane-bound fractions. Soluble and membrane-bound IRAP specific activities were assayed fluorometrically using leucyl-ß-naphthylamide as substrate. Prostate OT content was assayed by enzyme immunoassay. Doxazosin treatment significantly increased membrane-bound IRAP specific activity in rat prostate by 59.4%, whereas no changes were observed in the soluble fraction. Treatment with doxazosin also significantly increased OT concentration by 26.3%. In vivo administration of doxazosin to male rats modify both prostatic IRAP activity and OT levels. Because there is now evidence that OT plays a physiological role in the regulation of growth and muscular contractility within the gland, more attention should be paid to IRAP activity, which could represent a new target for the regulation of the functions of OT under physiological or pathological conditions such as BPH and prostate cancer.

Increased oxytocin concentrations and prosocial feelings in humans after ecstasy (3,4-methylenedioxymethamphetamine) administration

MDMA (3,4-methylenedioxymethamphetamine or “ecstasy”) is a recreationally used drug with remarkable and characteristic prosocial effects. In spite of abundant attention in the scientific literature, the mechanism of its prosocial effects has not been elucidated in humans. Recently, research in animals has suggested that the neuropeptide oxytocin may induce these effects. In a double blind, randomized, crossover, and placebo-controlled study in 15 healthy volunteers we assessed blood oxytocin and MDMA concentrations and subjective prosocial effects after oral administration of 100 mg MDMA or placebo. MDMA induced a robust increase of blood oxytocin concentrations and an increase of subjective prosocial feelings. Within subjects, the variations in these feelings were significantly and positively correlated with variation in oxytocin levels, and the correlations between these feelings and oxytocin were significantly stronger than those between these feelings and blood MDMA levels. MDMA induces oxytocin release in humans, which may be involved in the characteristic prosocial effects of ecstasy.

PVN electrical stimulation prolongs withdrawal latencies and releases oxytocin in cerebrospinal fluid, plasma, and spinal cord tissue in intact and neuropathic rats

We are studying an endogenous, oxytocinergic analgesia system to obtain more information about normal and pathological pain processes. In the recent years, this oxytocinergic system has been shown to be involved in normal and pathological pain suppression. The paraventricular nucleus (PVN) of the hypothalamus is an important source of brain oxytocin (OT). A descending pathway reaching the dorsal horn in the spinal cord was postulated to mediate analgesic effects at the spinal cord level. However, the oxytocin concentration during pain conditions and during PVN electrical stimulation needs to be determined. We designed experiments to measure the OT concentration in cerebrospinal fluid (CSF), plasma, and OT protein in lumbar spinal cord tissue in control and neuropathic rats. Sciatic loose ligature was used as the experimental method to produce neuropathic pain. The main findings were (1) Chronic pain experiments in animals showed that the stimulation of the anterior part of the PVN increased OT concentration and produced analgesia states, as measured by von Frey, cold, and heat plantar tests. (2) Differential effects were produced by electrical stimulation of the anterior or posterior regions of the PVN; electrical stimulation of the anterior part of the PVN enhanced the OT concentration in CSF and plasma, and it also increased OT protein concentrations in the spinal cord tissue; in contrast, the stimulation of the posterior part of the PVN only increased OT concentrations in CSF. These results suggest the participation of an endogenous analgesia system mediated by OT.

Effect of different milking routines on milking-related release of the hormones oxytocin, prolactin and cortisol, and on milk yield and milking performance in Murrah buffaloes

Milking-related release of oxytocin, prolactin, and cortisol was studied following three premilking treatments. Six Murrah buffaloes were treated with direct application of milking cluster (O), a 1-min pre-stimulation (M), and combined feeding and pre-stimulation (MF). Machine milk yield, stripping yield and milk composition were recorded. Milk ejection occurred significantly earlier with MF than M and O (P<0.05; 2.50, 5.10 and 6.33 min, respectively). In all treatments, milk ejection occurred with small increases >3-5 ng/l in oxytocin concentration. Increase in oxytocin concentration over a threshold level and milk ejection occurred simultaneously and were closely correlated (r=0.83, P<0.05). There was a positive correlation between total time oxytocin concentration remained elevated over threshold levels and machine yield (r=0.86, P<0.05). For treatment O, milk ejection was inhibited during machine milking, while a marked increase in oxytocin occurred during hand stripping (6 and 16 ng/l, respectively). For treatment M, mean oxytocin concentrations remained unchanged during prestimulation but increased during subsequent machine milking and hand stripping (6.38, 18.06 and 12.36 ng/l, respectively). For treatment MF, although there was a 3.6-fold increase during pre-stimulation, oxytocin increased by 10-fold and 3-fold during machine milking and hand stripping, and was significant for machine milking (P<0.05, 17.32, 47.86, 18.13 ng/l, respectively). Milk-ejection-related cortisol release was visible only in treatment MF. For treatments O and M, prolactin concentration increased prior to the increase in oxytocin. The stripping yield was higher, and fat content in the stripping yield significantly lower, for treatment O indicating incomplete milking. Thus buffaloes are easily disturbed even by small changes in milking routines.

Effects of steroids on oxytocin secretion by the human prostate in vitro.

Oxytocin (OT) concentrations are elevated in prostate tissue of patients with benign prostatic hyperplasia (BPH). Oxytocin specifically increases growth, 5 alpha-reductase activity and contractility in the prostate. In the rat prostatic OT concentrations are regulated by gonadal steroids, with androgens reducing but oestrogens increasing OT concentrations. The regulation of prostatic oxytocin in man is not understood. This study investigates the effects of gonadal steroids on oxytocin production by the human prostate. Primary explants (approx. 1 mm3) of prostate tissue from patients with BPH were incubated in Dulbecco's modified Eagle's media in the absence or presence of 10 nmol/L testosterone (T), 10 nmol/L dihydrotestosterone (DHT), T or DHT plus 100 nmol/L of the anti-androgen cyproterone acetate (CPA), 55 pmol/L diethylstilbestrol (DES), or DES plus DHT. The amount of oxytocin secreted into the media after 3 days was measured by radioimmunoassay. Testosterone and DHT significantly increased oxytocin concentrations secreted into the media from 0.86 +/- 0.11 ng/g of tissue (control) to 1.51 +/- 0.14 ng/g (p < 0.01) and 1.54 +/- 0.13 ng/g (p < 0.05), respectively. Incubation of tissue samples with CPA resulted in oxytocin concentrations similar to control levels. Treatment with DES caused a significant increase from 1.99 +/- 0.71 to 3.98 +/- 1.36 ng/g (p < 0.05). A similar increase was measured in media of tissue incubated in DES plus DHT (p < 0.001). The results demonstrate that, unlike the rat where androgens decrease oxytocin, in hyperplastic human prostate tissue both androgens and oestrogens increase oxytocin. This imbalance in the regulation of oxytocin may result in promoting prostatic overgrowth in the pathogenesis of BPH.

Oxytocin release and its relationship to dihydro-15-keto PGF2alpha and arginine vasopressin release during parturition and to suckling in postpartum mares

Pituitary blood was collected from the intercavernal sinus in five mares before and during parturition, and in nine mares immediately after parturition to investigate oxytocin patterns during parturition and early lactation, and to determine the relationship between oxytocin, prostaglandin and arginine vasopressin during parturition. In four mares in which sample collection began at least 6 h before rupture of the chorioallantois, a significant increase (P < 0.05) in PGF(2alpha) concentration was detected before a significant increase in oxytocin concentration. Cross-correlation analysis of log-transformed oxytocin and PGF(2alpha) concentrations revealed a significant correlation (P < 0.05) at a 6 min lag period, indicating that in the 2 h before delivery of the foal, an increase in prostaglandin was followed 6 min later by an increase in oxytocin. A significant effect of suckling on oxytocin release by the mare was detected in only two of nine mares, when oxytocin concentrations were evaluated 0-3 min after suckling. When foals were prevented from sucking for 1 h, by being either muzzled (n = 2) or separated from the mare (n = 2), there was no significant association between resumption of suckling and oxytocin release by the mare. The results of these studies show that: (i) oxytocin secretion from the maternal posterior pituitary gland begins before, or in association with, the onset of the second stage of labour, and that prostaglandin increases in the peripheral circulation before oxytocin release; and (ii) suckling is not significantly related to oxytocin release in mares.

C-fos and c-jun in the paraventricular nucleus play a role in regulating peptide gene expression, oxytocin and glutamate release, and maternal behaviour.

In sheep, birth leads to the induction of maternal behaviour through brain oxytocin release. Associated with these events is an upregulation of oxytocin, opioid and corticotrophin-releasing hormone (CRH) gene expression, as well as that of the immediate early gene c-fos in the paraventricular nucleus (PVN) of the hypothalamus. We investigated the role of c-fos dimerizing with c-jun in controlling the induction of maternal behaviour, altered peptide gene expression, and oxytocin and amino acid release in this region at birth. Fluorescence-labelled antisense oligodeoxyribonucleotides (ODNs) against c-fos/c-jun were infused bilaterally in the PVN, via microdialysis probes with 100 kDa cut-off membranes, and were incorporated into 50-60% of the cells. Compared with the control (scrambled) sequences, they significantly reduced basal concentration of glutamate (to 31.7% of baseline after 10 h) and prevented birth-induced release of aspartate. In addition, antisense treatment reduced the birth-induced increase in oxytocin concentration in the PVN, but not in blood. Although all the animals were fully maternal, the antisense treatment did reduce the peak expression of two components of maternal behaviour: low-pitched bleats; and lamb sniffing. Finally, in situ hybridization histochemistry revealed that the antisense treatment significantly reduced the birth-induced upregulation of c-fos, oxytocin, CRH and preproenkephalin mRNA expression in the PVN, whilst not affecting that of arginine vasopressin. These results suggest that c-fos/c-jun transcription factors play a role in the birth-induced upregulation of oxytocin, CRH and preproenkephalin gene expression, as well as on glutamate and oxytocin release in the sheep PVN.

Metabolism of oxytocin in rat uterus and placenta in late gestation.

Concentrations of oxytocin (OT) peptide increase in rat uterine tissues at the time of parturition. We have measured the rate of OT metabolism in these tissues in late gestation to determine whether a decrease in OT catabolism is responsible for the increase in OT concentrations. Uterine and placental tissues were obtained from groups of rats at Days 16, 19, 21, 21.5, 22, and after delivery of the first pup. Delivery usually occurs in the early afternoon of Day 22. Some animals were treated with the estrogen receptor blocker tamoxifen, which will delay parturition by approximately 24 h. Cytosolic and microsomal preparations obtained using ultracentrifugation were incubated with radiolabeled OT. Metabolites were separated using HPLC, and enzyme kinetic parameters were calculated. OT was actively metabolized in both uterine and placental tissues. Total oxytocinase activity was similar in the two tissues. In uterine tissues, activity was greater in the cytosolic fractions. In placenta, activity was evenly distributed between the cytosolic and microsomal fractions. The cytosolic fractions of each tissue contained predominantly post-proline endopeptidase activity, whereas the microsomes contained predominantly aminopeptidase activity. There was a slight trend to decreasing oxytocinase activity with advancing gestation in both subcellular fractions, but this was statistically significant only in the microsomal fraction. The maximal decline in activity was only 25-50%. Tamoxifen treatment had no effect on oxytocinase activity. We conclude that rat uterine and placental tissues contain post-proline endopeptidase and aminopeptidase activities that metabolize OT. It is doubtful that changes in these activities are major factors in regulating the increase in OT concentrations measured in rat intrauterine tissues at the time of parturition.

Cocaine's effect on plasma oxytocin concentrations in the baboon during late pregnancy

OBJECTIVE: The hypothesis for this investigation was that intravenous cocaine would result in an elevation of maternal plasma oxytocin levels in the baboon during late pregnancy. STUDY DESIGN: Five gravid chronically instrumented baboons had timed arterial blood samples obtained before and after an intravenous bolus cocaine infusion at least 5 days after surgery. Plasma oxytocin concentrations were measured by specific radioimmunoassays, and baseline samples were compared with postcocaine samples. RESULTS: The plasma oxytocin concentrations were significantly elevated at all sampling times after the 1.0 mg/kg cocaine dose ( p < 0.05). CONCLUSION: The increased oxytocin concentrations after cocaine use may be responsible for the increased incidence of preterm labor. (A M J O BSTET G YNECOL 1996;174:1026-7.)

Effect of 5-HT 1C and 5-HT 2 receptor stimulation on excessive grooming, penile erection and plasma oxytocin concentrations

Serotonin (5-HT) receptor agonist-induced excessive grooming, penile erection and oxytocin secretion were studied in chronically cannulated freely moving rats. The 5-HT 1C receptor agonists, m-chlorophenylpiperazine (m-CPP), which also binds to other 5-HT receptors, produced dose-dependent excessive grooming, penile erection and increases in circulating oxytocin concentrations. Maximal responses for excessive grooming and penile erection occured at 0.3–0.6 mg/kg i.v. m-CPP. Higher doses (0.9–2.5 mg/kg i.v.) caused further increases in oxytocin concentrations, but attenuated both behavioral responses. All three responses to m-CPP (0.6 mg/kg) were attenuated by antagonist with high affinity for the 5-HT 1C receptor site (mianserin, LY-53857 and metergoline), but not by the 5-HT 2 receptor antagonist ketanserin. The 5-HT 2/5-HT 1C agonist, 1-(2,5-dimenthoxy-4-iodophenyl)-2-aminopropane (DOI), increased plasma oxytocin concentrations only. After katanserin pretreatment, DOI caused penile erection and diminished the oxytocin response. All responses to DOI were blocked completely by pretreatment with LY-53857 plus ketanserin. Excessive grooming and penile erection showed significant bimodal correlations with the oxytocin response. These data suggest that stimulation of 5-HT 1C receptors induces excessive grooming, penile erection and increased oxytocin secretion. Stimulation of 5-HT 2 receptors causes a further increase in plasma oxytocin concentration, but inhibits both behavioral responses.

Plasma oxytocin during the first and second stages of spontaneous human labour.

A technique for complete oxytocinase inhibition has been combined with a rapid serial sampling strategy to determine plasma oxytocin concentrations in twelve women during the early and late first stage and in eight women throughout the second stage of labour. The progress of labour is not related to an increase in oxytocin concentration, uterine contractions are not associated with changes in plasma oxytocin concentration and hypocontractile labour does not appear to be the result of a deficit of oxytocin. The majority of patients do not demonstrate an increase in plasma oxytocin concentration during the second stage of labour; however, a minority produce a large surge immediately before delivery. The results do not support a role for oxytocin during spontaneous labour unless uterine activity is controlled by extremely low plasma hormone concentrations or the uterus becomes sensitive to a constant oxytocin concentration.

Oxytocin and vasopressin release in discrete brain areas after naloxone in morphine-tolerant and -dependent anesthetized rats: push-pull perfusion study

The effects of naloxone on the release of oxytocin and vasopressin in discrete brain areas were investigated in control and morphine-tolerant/dependent female rats anesthetized with urethane. Two or three consecutive push-pull perfusates were collected for 30-40 min each and the peptide contents measured by radioimmunoassay; naloxone (5 mg/kg, i.v.) was given after the first perfusion. In control rats, naloxone did not increase oxytocin release from any of the regions studied: mediolateral septum, dorsal hippocampus, nucleus of tractus solitarius, or supraoptic nucleus. After naloxone, vasopressin release was approximately doubled in the nucleus of tractus solitarius (p less than 0.05), indicating endogenous opioid inhibition of vasopressin release. Naloxone increased oxytocin concentration in the circulation 3.7-fold (p less than 0.001) but did not affect vasopressin secretion. In rats made morphine tolerant/dependent by intracerebroventricular infusion of morphine for 5 d, oxytocin and vasopressin release in the perfused brain was initially similar to that in control rats, indicating tolerance to any initial morphine effects. In these rats, naloxone increased oxytocin release in the septum threefold relative to control rats (p less than 0.02) but did not alter oxytocin release in hippocampus or nucleus of tractus solitarius. Thus, the oxytocin neurons projecting to septum can develop morphine dependence and may be inhibited acutely by opioids acting via mu-receptors. The results indicate morphine acts selectively on oxytocin neurons projecting to mediolateral septum compared with other central projection areas and compared with centrally projecting vasopressin neurons. In the supraoptic nucleus, naloxone increased oxytocin release 2.3-fold (from 9.2 +/- 3.1 pg/30 min) and increased oxytocin release from axons of these neurons fivefold (from 7.8 +/- 3.2 pg/30 min). Naloxone had no significant effect on vasopressin release from any of the central sites, or on vasopressin secretion into blood, although oxytocin secretion was increased 36-fold (from 17.2 +/- 2.6 pg/ml; p less than 0.001), confirming dependence of magnocellular oxytocin neurons. The central processes of magnocellular supraoptic neurons may be a major source of central oxytocin released during morphine withdrawal.