Temporary peripartal impairment in memory and attention and its possible relation to oxytocin concentration

The aim of the present study was to investigate peripartal performance on cognitive tests and its possible relationship with plasma oxytocin concentrations. Twenty women (cases) were tested on five experimental occasions, the first toward the end of pregnancy and the last 12 months postpartum. On each experimental occasion performance on cognitive tests of memory and attention was recorded and oxytocin concentrations were simultaneously assayed in plasma-samples. Twenty non-pregnant women (controls) were investigated at similar intervals. Cases were found to have improved their performance on some cognitive tests significantly more than controls when results at 6 and 12 months after delivery were compared with those from the end of pregnancy and up to three months after partus. This observation strongly suggests impairment in cognitive performance during the peripartal period. Cases had significantly higher oxytocin concentrations than controls in plasma samples up to three months post partum. No correlation was, however, found between cognitive test results and levels of oxytocin concentration.     

Behavioural actions of neurohypophysial peptides

The neurohypophysial hormones vasopressin and oxytocin modulate memory processes. Vasopressin facilitates while oxytocin attenuates memory consolidation and retrieval. These influences are located in different regions of the molecules. Thus, the neurohypophysial hormones act as precursor molecules for neuropeptides involved in memory processes. The covalent ring structures of both vasopressin and oxytocin mainly affect consolidation, the linear parts, retrieval processes, while nearly the whole oxytocin or vasopressin molecule is needed for attenuation of consolidation and retrieval. Regional studies by microdissection techniques in combination with a sensitive radioenzymatic catecholalmine assay, indicate that vasopressin modulates memory processes by modulation of neurotransmission in distinct catecholamine systems. Recent experiments suggest that the influence of vasopressin on memory consolidation is mediated by the dorsal noradrenergic bundle via terminal regions of this bundle. Studies on the conversion of oxytocin in synaptosomal plasma membrane preparations of rat limbic brain suggest the possible generation of fragments with specific effects on memory processes. Regional differences in enzyme activity further substantiate the implication of oxytocin as a prohormone in this respect. Clinical studies support the evidence from laboratory findings that vasopressin is also involved in memory processes in man.     

Menstrual cycle-related changes in plasma oxytocin are relevant to normal sexual function in healthy women

Circulating levels of the neuro-hypophysial nonapeptide oxytocin increase during sexual arousal and orgasm in both men and women. A few studies have evaluated the effect of the menstrual cycle on plasma oxytocin in normally cycling, sexually active, healthy fertile women using or not using contraceptive pills. In 20 ovulating women and 10 women taking an oral contraceptive (group 1 and group 2, respectively), sexual function, hormonal profile, and plasma oxytocin (OT) were evaluated throughout the menstrual cycle. In group 1, plasma OT was significantly lower during the luteal phase in comparison with both the follicular and ovulatory phases. Plasma oxytocin was significantly correlated with the lubrication domain of the Female Sexual Function Index (FSFI) during the luteal phase and showed a trend towards statistical significance during the follicular phase. In group 2, plasma OT did not show any significant fluctuation throughout the menstrual cycle, even though a significant correlation was evident with both the arousal and the lubrication domain of the FSFI during the assumption of the contraceptive pill. These findings suggest that plasma OT fluctuates throughout the menstrual cycle in normally cycling healthy fertile women with adequate sexual activity but not taking any oral contraceptive pill. Moreover, plasma OT levels significantly relates to the genital lubrication in both women taking and not taking oral contraceptive pill apparently confirming its role in peripheral activation of sexual function.     

Neurohypophyseal principles and memory.

The neurohypophyseal hormones vasopressin and oxytocin modulate memory processes. Vasopressin facilitates, while oxytocin attenuates memory consolidation and retrieval. These influences are located in different regions of the molecules. Thus, the neurohypophyseal hormones act as precursor molecules for neuropeptides involved in memory processes. The covalent ring structures of both vasopressin and oxytocin mainly affect consolidation; the linear parts, retrieval processes; while nearly the whole oxytocin or vasotocin molecule is needed for attenuation of consolidation and retrieval. Regional studies, utilizing microdissection techniques in combination with a sensitive radioenzymatic catecholamine assay, revealed a distinct pattern of effects on cerebral alpha-methyl-p-tyrosine methylester-induced catecholamine disappearance following intraventricular vasopressin administration in limbic midbrain structures. In situations in which the amount of bioavailable vasopressin in the brain is absent, as is the case in the Brattleboro rat with hereditary diabetes insipidus, or neutralized in normal Wistar rats following the intraventricular administration of antivasopressin serum, regional catecholamine disappearance in most cases is altered in a direction opposite to that observed after intracerebroventricular vasopressin administration. These results indicate that vasopressin modulates memory processes by modulation of neurotransmission in distinct catecholamine systems. Recent experiments suggest that the influence of vasopressin on memory consolidation is mediated by the dorsal noradrenergic bundle via terminal regions of this bundle.     

Sexual dimorphism in oxytocin responses to health perception and disgust,with implications for theories on pathogen detection

In response to a recent hypothesis that the neuropeptide oxytocin might be involved in human pathogen avoidance mechanisms, we report the results of a study in which we investigate the effect of intranasal oxytocin on two behaviors serving as proxies for pathogen detection. Participants received either oxytocin or a placebo and were asked to evaluate (1) the health of Caucasian male computer-generated pictures that varied in facial redness (an indicator of hemoglobin perfusion) and (2) a series of pictures depicting disgusting scenarios. Men, but not women, evaluated all faces, regardless of color, as less healthy when given oxytocin compared to a placebo. Women, on the other hand, expressed decreased disgust when given oxytocin compared to a placebo. These results suggest that intranasal oxytocin administration does not facilitate pathogen detection based on visual cues, but instead reveal clear sex differences in the perception of health and sickness cues.     

Oxytocin enhances onset of lactation among mothers delivering prematurely.

In a double-blind group sequential trial the efficiency of an oxytocin nasal spray in enhancing lactation was studied during the first five days after delivery in women who had given birth prematurely. The cumulative volume of breast milk obtained between the second and fifth days after delivery was 3.5 times greater in primiparas given oxytocin than in primiparas given placebo. There was no significant difference in the composition of the milk between the untreated women and those given oxytocin. The results of this study show that oxytocin nasal spray is an effective and safe means of enhancing lactation in women using a breast pump.     

Effect of prostaglandins on milk ejection.

Prostaglandins (PGs) of type F2 alpha, E1, and E2 have been reported both, to inhibit or to facilitate posterior pituitary oxytocin release in lactating animals and women, and to suppress or to stimulate the mammary myoepithelium. Prostaglandin-induced milk ejection in women and cows has been attributed to central oxytocin release, but no oxytocin blood levels were determined. Moreover, for lactating cows, sows, rabbits, guinea pigs, and rats a direct PG effect on the mammary myoepithelium resulting in milk ejection has been suggested. On the other hand, PGs were found to antagonize the milk-ejection response to oxytocin in rabbits and rats. The mechanisms involved in PG synergism or antagonism of oxytocin-induced milk ejection are not understood. Studies in lactating rats showed that blood pressure active PG doses of F2 alpha, E1, and E2 largely inhibited the intramammary pressure response to oxytocin. Whereas the oxytocin-antagonistic action of PGF2 alpha was not affected by adrenergic blockers (phenoxybenzamine, propranolol), the anti-oxytocin effects of PGE1 and E2 were eliminated after alpha-receptor blockade while the activity of oxytocin increased. Under beta-receptor or alpha- plus beta-receptor blockade, the oxytocin-inhibitory effects of PGE1 and E2 were almost abolished. Mechanisms of PG-induced inhibition of the oxytocin response may involve mammary vascular changes and/or alterations in myoepithelial activity of cyclic adenosine-3,5-monophosphate (c-AMP), cyclic guanosine-3,5-monophosphate (c-GMP), and phosphodiesterase (PDE). It seems unlikely that PGs bring about significant posterior pituitary oxytocin release in rats.     

Dose dependent effects of oxytocin on cognitive defects and anxiety disorders in adult rats following acute infantile maternal deprivation stress

ABSTRACT

Maternal deprivation at an early age is a powerful stressor that causes permanent alterations in cognitive and behavioral functions during the later stages of life. We investigated the effects of oxytocin on cognitive defects and anxiety disorders caused by acute infantile maternal deprivation in adult rats. We used 18-day-old Wistar albino rats of both sexes. The experimental groups included control (C), maternally deprived (MD), maternally deprived and treated with 0.02 μg/kg oxytocin (MD-0.02 µg/kg oxy), maternally deprived and treated with 2 μg/kg oxytocin (MD-2 µg/kg oxy). When the rats were 60 days old, the open field (OF) and elevated plus maze (EPM) behavioral tests, and the Morris water maze (MWM) test for spatial learning and memory were performed. In addition, the number of neurons in the hippocampus, prefrontal cortex (PFC) and amygdala were determined using quantitative histology. We also measured vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) levels in the PFC. In both sexes, the MD group failed the learning test and the MD-2 μg/kg oxy group failed in the memory test. The MD-0.02 μg/kg oxy group spent more time in the open arm of the EPM device and their locomotor activities were greater in the OF test. The VEGF and BDNF levels in the PFC were higher in the MD-0.02 μg/kg oxy groups than the other maternally deprived groups (oxytocin ±). The number of PFC neurons was low in all male maternally deprived (oxytocin ±) groups, while the number of amygdala neurons was low in both female and male maternally deprived (oxytocin ±) groups. Male rats were more affected by maternal deprivation; administration of oxytocin had dose-dependent biphasic effects on learning, memory and anxiety.     

Oxytocin and Social Preference in Female House Mice (Mus musculus domesticus)

In social species, same‐sex individuals may form social bonds behaviourally expressed as individual preferences, resulting in fitness benefits such as increased offspring survival, longevity and group cohesion. As a result of individual preferences, female house mice (Mus musculus domesticus) form social affiliations while communally nursing and may do so with kin or non‐kin. However, the mechanisms behind the formation of such preferences are unknown. Oxytocin has been linked to a range of social behaviours including bond facilitation, social memory and parental care. Here, we experimentally increased oxytocin in pairs of unfamiliar, unrelated females and predicted that females with elevated oxytocin would demonstrate increased affiliative behaviours compared against a control. Subsequently, we tested for the formation of a social preference, using a preference test with the previous partner and a new unfamiliar female. Our results indicated no significant effect of treatment on positive and negative behaviours between females during the three initial cohabitation days. In both treatments, females demonstrated increased socio‐positive behaviours and cohabitation time with their partner and decreased socio‐negative behaviours and latency to meet, over the 3‐d period. During the partner preference test, control but not oxytocin females demonstrated a significant preference for their cohabitation partner, and oxytocin females spent similar amounts of time with both stimulus females. Therefore, increasing peripheral oxytocin appears not to be involved in the facilitation of initial encounters with a stranger but may hinder the formation of a preference for this new partner.     

Oxytocin attenuates deficits in social interaction but not recognition memory in a prenatal valproic acid-induced mouse model of autism

Recent studies have reported that oxytocin ameliorates behavioral abnormalities in both animal models and individuals with autism spectrum disorders (ASD). However, the mechanisms underlying the ameliorating effects of oxytocin remain unclear. In this study, we examined the effects of intranasal oxytocin on impairments in social interaction and recognition memory in an ASD mouse model in which animals are prenatally exposed to valproic acid (VPA). We found that a single intranasal administration of oxytocin restored social interaction deficits for up to 2 h in mice prenatally exposed to VPA, but there was no effect on recognition memory impairments. Additionally, administration of oxytocin across 2 weeks improved prenatal VPA-induced social interaction deficits for at least 24 h. In contrast, there were no effects on the time spent sniffing in control mice. Immunohistochemical analysis revealed that intranasal administration of oxytocin increased c-Fos expression in the paraventricular nuclei (PVN), prefrontal cortex, and somatosensory cortex, but not the hippocampal CA1 and CA3 regions of VPA-exposed mice, suggesting the former regions may underlie the effects of oxytocin. These findings suggest that oxytocin attenuates social interaction deficits through the activation of higher cortical areas and the PVN in an ASD mouse model.     

Molecular cloning and expression of a new gene,GON-SJTU1 in the rat testis

Background

A prolonged latent phase is independently associated with an increased incidence of subsequent labor abnormalities. We aimed to compare between oxytocin augmentation, amniotomy and a combination of both on the duration of labor among women with a prolonged latent phase.

Methods

Women with a singleton fetus in cephalic presentation who have a prolonged latent phase, were randomly allocated to amniotomy (group 1), oxytocin (group 2) or both (group 3). A group of women who progressed spontaneously without intervention composed the control group (group 4). The primary outcome was the duration of time from initiation of augmentation until delivery.

Results

A total of 213 women were consented and randomized to group 1 (70 women), group 2 (72 women) and group 3 (71 women). Group 4 was composed from additional 70 women. A mean reduction of 120 minutes in labor duration was observed among group 3 compared to group 1 (p = 0.08) and 180 minutes compared to group 2 and 4 (p = 0.001). Women in group 3 had a shorter length of time from augmentation until the beginning of the active phase and a shorter first stage of labor than group 1 (p = 0.03), group 2 (p = 0.001) and group 4 (p = 0.001). Satisfaction was greater among group 3 and 4. Mode of delivery and neonatal outcome were comparable between the groups.

Conclusion

Labor augmentation by combined amniotomy and oxytocin among women with a prolonged latent phase at term seems superior compared to either of them alone.     

Oxytocin increases VTA activation to infant and sexual stimuli in nulliparous and postpartum women

After giving birth, women typically experience decreased sexual desire and increased responsiveness to infant stimuli. These postpartum changes may be viewed as a trade-off in reproductive interests, which could be due to alterations in brain activity including areas associated with reward. The goal of this study was to describe the roles of oxytocin and parity on reward area activation in response to reproductive stimuli, specifically infant and sexual images. Because they have been shown to be associated with reward, the ventral tegmental area (VTA) and nucleus accumbens (NAc) were targeted as areas of expected alterations in activity. Oxytocin was chosen as a potential mediator of reproductive trade-offs because of its relationship to both mother–infant interactions, including breastfeeding and bonding, and sexual responses. We predicted that postpartum women would show higher reward area activation to infant stimuli and nulliparous women would show higher activation to sexual stimuli and that oxytocin would increase activation to infant stimuli in nulliparous women. To test this, we measured VTA and NAc activation using fMRI in response to infant photos, sexual photos, and neutral photos in 29 postpartum and 30 nulliparous women. Participants completed the Sexual Inhibition (SIS) and Sexual Excitation (SES) Scales and the Brief Index of Sexual Function for Women (BISF-W), which includes a sexual desire dimension, and received either oxytocin or placebo nasal spray before viewing crying and smiling infant and sexual images in an fMRI scanner. For both groups of women, intranasal oxytocin administration increased VTA activation to both crying infant and sexual images but not to smiling infant images. We found that postpartum women showed lower SES, higher SIS, and lower sexual desire compared to nulliparous women. Across parity groups, SES scores were correlated with VTA activation and subjective arousal ratings to sexual images. In postpartum women, sexual desire was positively correlated with VTA activation to sexual images and with SES. Our findings show that postpartum decreases in sexual desire may in part be mediated by VTA activation, and oxytocin increased activation of the VTA but not NAc in response to sexual and infant stimuli. Oxytocin may contribute to the altered reproductive priorities in postpartum women by increasing VTA activation to salient infant stimuli.     

The Association between Oxytocin and Social Capital

Background

Oxytocin is known to be related to social behaviors, including trust. However, few studies have investigated the association between oxytocin levels and social capital. Thus, we tested the hypothesis that endogenous oxytocin levels are positively associated with social capital. We also considered whether the association differed across gender because previous studies have shown differential effects of OT on social behaviors depending on gender.

Methods

We recruited a convenience sample of 50 women and 31 men in Japan via community sampling from whom we obtained urine sample with which to measure oxytocin levels. Individual-level cognitive social capital (social trust and mutual aid) and structural social capital (community participation) were assessed using a questionnaire. We used multivariate regression, adjusted for covariates (age, number of children, self-rated health, and education), and stratified by gender to consider associations between oxytocin and social capital.

Results

Among women, oxytocin was inversely associated with social trust and mutual aid (p<0.05). However, women participating in only 1 organization in the community showed higher oxytocin than women who participated in either no organizations (p<0.05) or 2 or more organization (i.e. inverse-U shape association). Among men, no association was observed between oxytocin and either form of cognitive and structural social capital.

Conclusion

Women who perceived low cognitive social capital showed higher oxytocin levels, while structural social capital showed inverse-U shape association with oxytocin. No association between oxytocin and social capital was found among men. Further study is needed to elucidate why oxytocin was inversely associated with cognitive social capital only among women.     

Plasma oxytocin during third stage of labour: comparison of natural and active management.

The incidences of postpartum haemorrhage and retained placenta have decreased with the use of synthetic oxytocin and controlled cord traction. Whether such treatment is valuable is open to question because of the lack of clinical and physiological studies. The physiological effects of synthetic oxytocin on plasma concentrations of oxytocin and events during delivery were assessed. Plasma oxytocin concentration was determined in serial samples during the late second stage and throughout the third stage of labour in 25 women. Ten women received combined ergotamine and synthetic oxytocin intramuscularly and 15 were not treated. The geometric mean plasma oxytocin concentration significantly increased in the women given oxytocin when measured before and after delivery of the fetal anterior shoulder (3.1 (SD 2.0) pmol/l before and 15.9 (2.7) pmol/l after). Six of the women who did not receive treatment showed a significant increase in geometric mean plasma oxytocin concentration before and after delivery of the fetal shoulder (3.2 (2.0) pmol/l before and 6.4 (2.0) pmol/l after) and nine did not show an increase (geometric mean 2.4 (3.1) pmol/l before and 2.2 (2.2) pmol/l after). Of these nine women, two had an abnormal third stage of delivery; one woman had a postpartum haemorrhage and one required manual removal of the placenta. As it is impossible to predict which women will show a rise in the plasma concentration of endogenous oxytocin, intramuscular oxytocin should be given routinely.     

The influence of offspring,parity, and oxytocin on cognitive flexibility during the postpartum period

Pregnancy and the postpartum period are times of profound behavioral change including alterations in cognitive function. This has been most often studied using hippocampal-dependent tasks assessing spatial learning and memory. However, less is known about the cognitive effects of motherhood for tasks that rely on areas other than the hippocampus. We have previously shown that postpartum females perform better on the extradimensional phase of an attentional set shifting task, a measure of cognitive flexibility which is dependent on the medial prefrontal cortex (mPFC). The present experiments aimed to extend this work by examining the importance of postpartum stage as well as offspring and parity in driving improved mPFC cognitive function during motherhood. We also examined whether the neuropeptide oxytocin, which plays a role in regulating numerous maternal functions, mediates enhanced cognitive flexibility during motherhood. Our results demonstrate that compared to virgin females, cognitive flexibility is enhanced in mothers regardless of postpartum stage and is not affected by parity since both first (primiparous) and second (biparous) time mothers showed the enhancement. Moreover, we found that improved cognitive flexibility in mothers requires the presence of offspring, as removal of the pups abolished the cognitive enhancement in postpartum females. Lastly, using an oxytocin receptor antagonist, we demonstrate that oxytocin signaling in the mPFC is necessary for the beneficial effects of motherhood on cognitive flexibility. Together, these data provide insights into the temporal, experiential and hormonal factors which regulate mPFC-dependent cognitive function during the postpartum period.     

Effects of oxytocin outside pregnancy

For a long time, oxytocin was regarded as a pregnancy hormone released by the hypophysis to stimulate labour and milk ejection. In the present survey, data have been collected from the literature to show the spectrum of the hitherto known functions of oxytocin outside pregnancy. It is now known that oxytocin receptors can occur almost ubiquitously in the organism, that oxytocin is also formed outside of the brain and that oxytocin has functions in a number of organs. In the first part of the survey, stimuli that contribute to an increase in oxytocin release are compiled. In the second part, details are given on the individual oxytocin targets. Although the majority of findings are based on the results of animal experiments, there are already a number of studies that indicate similar effects of oxytocin in humans. According to the current state of knowledge, oxytocin appears to be involved in functions in the following organs: male and non-pregnant female reproductive tract, pancreas, cardiovascular system, kidney, brain and breast. There are indications that oxytocin may also have actions in other organs. There continues to be a considerable need for research into oxytocin in order to better understand the physiological and pathophysiological actions and to be able to derive possible therapeutic uses. Further light on the spectrum of functions of oxytocin may be cast by the possibility of the use of oxytocin antagonists.     

Effects of pregnancy and labor on oxytocin levels in human plasma and cerebrospinal fluid

In order to investigate the significance of oxytocin in pregnancy and labor, oxytocin concentrations in plasma and cerebrospinal fluid (CSF) were determined using the specific radioimmunoassay. Plasma and CSF samples were obtained from 23 pregnant women (11 pre labor, 12 in labor), 15 nonpregnant women and 4 men at spinal puncture for anesthesia. In males and nongravidas, CSF levels of oxytocin were significantly higher than plasma levels. Plasma levels in pregnant patients pre or in labor were significantly higher than those in nongravidas. No significant difference between CSF levels in prelabor gravidas (mean +/- SE, 9.7 +/- 1.5 mu u/ml) and nongravidas (10.1 +/- 1.2 mu u/ml) was found. However, CSF levels in gravidas in labor (18.6 +/- 2.3 micromicrons/ml were significantly higher than the levels in prelabor gravidas. These results strongly suggest that oxytocin levels in human plasma and CSF are controlled by different mechanisms and that the increased oxytocin could have some specific central actions.     

Separation Anxiety,Attachment and Inter-Personal Representations: Disentangling the Role of Oxytocin in the Perinatal Period

In this paper, we aimed to assess cross-sectionally and longitudinally associations between disturbances in maternal early attachment experiences, symptoms of separation anxiety and depression and oxytocin plasma levels. We examined a mediational model that tested the hypothesis that anxious attachment style arising from the mothers’ early bonding experiences with her own parents was associated with high levels of separation anxiety which, via its impact on depression, was associated with reduced levels of oxytocin in the postnatal period. Data is reported on a structured sample of 127 women recruited during pregnancy from a general hospital antenatal clinic and an initial follow up cohort of 57 women who were re-assessed at 3-months post-partum. We found an association between lower oxytocin level in the post partum period and symptoms of separation anxiety and depression during pregnancy, as well as maternal negative interpersonal representations, upbringing attributes and anxious attachment style. Further meditational analysis revealed that the unique association between anxious attachment and depression is mediated by separation anxiety and that depressed mood mediated the relationship between separation anxiety and oxytocin. In conjunction with evidence from the literature suggesting that lower oxytocin level is associated with bonding difficulties, our findings have significant implications for understanding the biological processes underpinning adverse attachment experiences, negative affect state, and mother-to-infant bonding difficulties.     

Induction of therapeutic abortion using either extra-amniotic prostaglandin F-2-alpha or hypertonic saline followed by oxytocin

160 women with uteri at 10-20 weeks gestation were treated with either PG(prostaglandin)F2alpha or saline solution followed by oxytocin to effect an abortion. 80 women were in each treatment group. The distribution of the patients according to age, parity, and gestation duration is tabulated. PGF2alpha was administered extraovularly in a concentration of .1 mg/ml with .7 mg being injected in the operating theater and nurses administering the rest based on response to previous injections. Administration continued for up to 30 hours. Saline was given in a volume in ml dependent on the duration of pregnancy multiplied by a factor of 10. Subcutaneous injections of oxytocin were given on subsequent days to speed the abortion. 85% of the PG patients successfully aborted without surgical dilatation of the cervix. The average dosage of PG required was 7.5 mg in 11 instillations. Side effects and complications in the PG group were minimal. 1 instillation of saline followed by 2 days of oxytocin were required to effect a 79% abortion rate in the saline group. Although the number of patients requiring surgical dilatation was the same for both groups, the procedure was much less time-consuming for the PG group. The complication rate was 26% for the saline group as compared to 14% for the PG group. The PG group required a shorter hospital stay.