From Parental Behavior to Sexual Function: Recent Advances in Oxytocin Research.

Purpose of Review: Oxytocin plays many diverse roles in physiological and behavioral processes, including social activity, parental nurturing, stress responses, and sexual function. In this narrative review, we provide an update on the most noteworthy recent findings in this fascinating field. Recent Findings: The development of techniques such as serial two-photon tomography and fiber photometry have provided a window into oxytocin neuroanatomy and real-time neuronal activity during social interactions. fMRI and complementary mapping techniques offer new insights into oxytocin's influence on brain activity and connectivity. Indeed, oxytocin has recently been found to influence the acquisition of maternal care behaviors and to mediate the influence of social touch on brain development and social interaction. Additionally, oxytocin plays a crucial role in male sexual function, affecting erectile activity and ejaculation, while its role in females remains controversial. Recent studies also highlight oxytocin's interaction with other neuropeptides, such as melanin-concentrating hormone, serotonin, and arginine vasopressin, influencing social and affective behaviors. Finally, an update is provided on the status of clinical trials involving oxytocin as a therapeutic intervention. Summary: The exploration of oxytocin's complexities and its interplay with other neuropeptides holds promise for targeted treatment in various health and disease contexts. Overall, these findings contribute to the discovery of new and specific pathways to allow therapeutic targeting of oxytocin to treat disorders.

The effect of flow-responsive vacuum and pulsation with early attachment of milking unit on teat tissue condition and milking performance in Holstein dairy cows.

The objectives of this study were to assess the effect of flow-responsive vacuum and pulsation, in conjunction with the early attachment of the milking unit (TRT), on teat tissue conditions and milking characteristics in dairy cows. In a switch-back trial, 5,235 Holstein cows milked 3 times daily in a rotary parlor were assigned to the TRT or control (CON) group. The trial lasted 84 d and was comprised of 4 alternating 3-week periods of TRT and CON. For both groups, premilking udder preparation consisted of teat brushing, forestripping and predipping, and wiping of teats, resulting in a stimulation time of 4 s. In the TRT group, the preparation lag time was 58 s, and in the CON group, it was 91 s for early- and mid-lactation cows and 105 s for late-lactation animals. Upon milking unit attachment, the TRT cows were milked at a lower vacuum (37.6 kPa) and pulsation (50 cycles/min, pulsation ratio of 30:70). The vacuum and pulsation settings were changed to milking mode when the milk flow reached 0.5 kg/min (pulsation switch-point) and 1.6 kg/min (vacuum switch-point). For milking mode, the vacuum setting was 47.7 kPa, and the pulsation rate was 60 cycles/min at a ratio of 65:35. The CON cows were milked with a flow-responsive vacuum, using the same vacuum settings as the TRT group. We assessed machine milking-induced short-term teat tissue changes and teat-end hyperkeratosis by palpation and visual inspection postmilking. Electronic on-farm milk meters were used to assess milking characteristics. Generalized linear mixed models were used to analyze the effect of treatment on the outcome variables. Compared with cows in group CON, the odds ratios (95% confidence interval; 95% CI) of short-term teat-tissue changes in early-, mid-, and late lactation cows in group TRT were 0.62 (0.52-0.76), 0.61 (0.48-0.77), and 0.93 (0.76-1.14), respectively. The least squares means [LSM, (95% CI)] for milking unit-on time in early-, mid-, and late lactation animals, respectively, were 251 (248-253), 236 (234-238), and 220 (218-222) s for group TRT and 247 (245-249), 232 (230-234), and 214 (213-216) s for the CON group. The LSM (95% CI) of peak milk flow rate in early-, mid-, and late lactation animals, respectively, were 5.75 (5.68-5.82), 5.77 (5.70-5.84), and 5.54 (5.48-5.59) kg/min for the TRT cows and 5.65 (5.58-5.72), 5.74 (5.68-5.81), and 5.45 (5.40-5.51) kg/min for the CON cows. The odds ratios (95% CI) of forced take-off in group TRT for early-, mid-, and late lactation cows, respectively, were 0.39 (0.37-0.41), 0.32 (0.30-0.34), and 0.47 (0.44-0.52) compared with their respective CON groups. In this study, cows that were milked using flow-responsive vacuum and pulsation with early attachment of the milking unit had lower odds of short-term teat tissue changes and forced take-off, as well as a higher peak milk flow rate. Our data suggest that the application of flow-responsive vacuum and pulsation facilitates early attachment of the milking unit, improves teat tissue condition, and has the potential to improve parlor efficiency.

Investigation of effect peripheral kisspeptin treatment on hypothalamo-pituitary-gonadal axis and hypothalamo-pituitary-adrenal axis in male rats.

Kisspeptin is an endogenous peptide hormone that is the most potent stimulator of the hypothalamo-pituitary-gonadal (HPG) axis. The HPG axis can be suppressed by the activation of the hypothalamo-pituitary-adrenal (HPA) axis. The physiological role of kisspeptin in the interaction of the HPG axis and the HPA axis is not fully understood yet. The purpose of the current study was to investigate the possible effects of peripheral injection (intraperitoneally) of kisspeptin on HPG axis and HPA axis activity as well. Adult male Wistar rats were randomly divided into seven groups as sham (control), kisspeptin (10 nmol), p234 (10 nmol), kisspeptin + p234, kisspeptin + antalarmin (10 mg/kg), kisspeptin + astressin2b (100 µg/kg), and kisspeptin + atosiban (0.250 mg/kg) (n = 10 each group). At the end of the experiment, the hypothalamus, pituitary gland, and serum samples of the rats were collected. Serum follicle-stimulating hormone and luteinizing hormone levels of the kisspeptin, kisspeptin + antalarmin and kisspeptin + astressin2b groups were significantly higher than the control group. Serum testosterone levels were significantly higher in the kisspeptin, kisspeptin + antalarmin, kisspeptin + astressin2b, and kisspeptin + atosiban groups that compared to the control group. There was no a significant difference in corticotropic releasing hormone immunoreactivity in the paraventricular nucleus of the hypothalamus, serum adrenocorticotropic hormone and corticosterone concentrations among all groups. Moreover, no significant difference was found in the concentration of pituitary oxytocin. Our results suggest that peripheral kisspeptin injection induces an activation in the HPG axis, but not in the HPA axis in male rats.

A single intravenous reelin injection restores corticosterone-induced neurochemical and behavioral alterations in dams during the post-partum period.

Introduction: Treatment with the synaptic plasticity protein reelin has rapid antidepressant-like effects in adult corticosterone (CORT)-induced depressed rats, whether administered repeatedly or acutely. However, these effects remain unexplored in the context of post-partum depression (PPD). Methods: This study investigated the antidepressant-like effect of a single injection of reelin in a CORT-induced model of PPD. Long-Evans female dams received either daily subcutaneous CORT (40 mg/kg) or saline injections (controls) from the post-partum day (PD) 2 to 22, and on PD22 were treated with a single intravenous reelin (3 µg) or vehicle injection. Results: Reelin treatment fully normalized to control levels the CORT-induced increase in Forced Swim Test (FST) immobility and the decrease in reelin-positive cells in the subgranular zone of the intermediate hippocampus. It also increased the number of oxytocin-positive cells in the paraventricular nucleus (PVN), the number of reelin-positive cells in the dorsal and ventral hippocampus, and the dendritic complexity of newborn neurons in the intermediate hippocampus, causing a partial recovery compared to controls. None of these changes were associated with fluctuations in estrogen levels measured peripherally. Discussion: This study brings new insights into the putative antidepressant-like effect of peripherally administered reelin in an animal model of PPD. Future studies should be conducted to investigate these effects on a dose-response paradigm and to further elucidate the mechanisms underlying the antidepressant-like effects of reelin.

Interplay of MeCP2/ REST/ Synaptophysin-BDNF and intranasal oxytocin influence on Aß-induced memory and cognitive impairments.

BACKGROUND: Alzheimer's disease (AD) is linked to the accumulation of Aß, increased tau hyperphosphorylation, persistent neuroinflammation, and a decline in neurotrophic factors, neurogenesis, and synaptic plasticity. Oxytocin (OT) has a significant impact on memory and learning. We examined the influence of intranasal (IN) OT on synaptic plasticity, neurogenesis, histone acetylation, and spatial and cognitive memories in rats. METHODS: Aß25-35 (5µg/2.5µl) was administered bilaterally in the CA1 of male Wistar rats for four consecutive days. After 7 days of recovery, OT (2µg/µl, 10µl in each nostril) was administered IN for seven consecutive days. Working, spatial, and cognitive memories, and gene expression of neurogenesis and synaptic plasticity involved factors were measured in the hippocampus. Histone acetylation (H3K9 and H4K8) was also measured using western blotting. RESULTS: IN OT significantly improved working and spatial memory impairment induced by Aß. The factors involved in synaptic plasticity (MeCP2, REST, synaptophysin, and BDNF) and neurogenesis (Ki67 and DCX) were also significantly increased by IN administration of OT. We also found an enhancement in the levels of H3K9ac and H4K8ac following OT administration. CONCLUSION: These findings indicated that IN OT could improve hippocampus-related behaviors by increasing synaptic plasticity, stimulating neurogenesis, and chromatin plasticity.

The relationship between cardiac activity, behaviour and endogenous oxytocin and vasopressin in Prader-Willi Syndrome: An exploratory study.

This study aimed to increase our understanding of cardiac activity abnormalities in Prader-Willi Syndrome (PWS) and the relationship between cardiac activity, PWS behaviours thought to be associated with cardiac vagal tone and endogenous oxytocin and vasopressin levels. We compared cardiac activity (respiratory sinus arrhythmia (RSA), low-frequency heart rate variability (LF-HRV), heart period) in 30 adolescents and adults with PWS to 30 typically developing age-matched controls. RSA, LF-HRV, and heart period were lower in individuals with PWS than in the control group. In the control group, RSA was higher for females than males. However, for those with PWS, there was no difference between the sexes. Individuals with the mUPD genetic subtype had lower RSA and LF-HRV than participants with the PWS deletion subtype and compared to typically developing controls, no difference was found between the latter two groups. Heart period was also lower for those with mUPD compared to controls. Higher RSA reduced the odds of having temper outbursts and skin-picking. RSA was lower in those with PWS and psychosis compared to those with PWS without psychosis. Finally, we found RSA correlated with vasopressin for those with mUPD but not deletion. There was no relationship between RSA and oxytocin plasma or saliva levels. Our findings suggest autonomic dysfunction in PWS that is more marked in mUPD than deletion and potentially due to greater loss of parasympathetic activity in mUPD.

The Oxytocinergic System and Racial Ingroup Bias in Empathic Neural Activity.

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

Sex-specific effects on elements of the social brain neural network in Wistar rats from perinatal exposure to FireMaster 550 or its components.

Developmental exposure to chemical flame retardants (FRs) has been linked to a variety of neurodevelopmental disorders and abnormal socioemotional behaviors in human and laboratory animal studies. We have previously shown in Wistar rats that gestational and lactational exposure to the FR mixture Firemaster 550 (FM 550) or its brominated or organophosphate ester (OPFR) components (at 2,000µg, 1,000µg, and 1,000µg oral to the dam respectively) results in increased anxiety-like behaviors in females and decreased sociality in both sexes. Using their siblings, this study characterized sex and chemical specific targets of disruption in brain regions underlying each behavioral phenotype. Offspring were exposed across gestation and lactation then prepared for either immunohistochemistry or autoradiography at postnatal day 90 to quantify expression of serotonin, estrogen receptor α (ERα), and oxytocin receptor (OTR) in multiple brain regions. No effect of exposure was found in males for any biological target. In females, serotonin innervation was increased in the medial amygdala of FM 550 exposed animals while ERα expression in the bed nucleus of the stria terminalis (BNST) was reduced by FM 550 and OPFR. Evidence of disrupted OTR was observed in males, particularly the BNST but considered an exploratory finding given the small sample size. These results begin to shed light on the mechanisms by which developmental FR exposure alters socioemotional behaviors of relevance to neurodevelopmental disorders.

The Effects of Testosterone on Hypothalamic and Serum Oxytocin Levels Are Affected by the Estrogen Milieu in Female Rats.

Previous studies have suggested that the effects of androgens on body weight (BW) and appetite are affected by the estrogen milieu in females; however, the mechanism underlying these effects remains unclear. We hypothesized that androgens may affect endogenous oxytocin (OT), which is a hypothalamic anorectic factor, and that these effects of androgens may be altered by the estrogen milieu in females. To investigate this hypothesis, in the present study, we examined the effects of testosterone on peripheral and central OT levels in ovariectomized female rats that did or did not receive estradiol supplementation. Ovariectomized female rats were randomly divided into non-estradiol-supplemented or estradiol-supplemented groups, and half of the rats in each group were concurrently supplemented with testosterone (i.e., rats were divided into four groups, n = 7 per each group). We also measured peripheral and central OT receptor (OTR) gene expression levels. As a result, we found that testosterone increased serum and hypothalamic OT levels and OT receptor mRNA levels in non-estradiol-supplemented rats, whereas it had no effects on these factors in estradiol-supplemented rats. In addition, testosterone reduced food intake, BW gain, and fat weight in non-estradiol-supplemented rats, whereas it did not have any effects on BW, appetite, or fat weight in estradiol-supplemented rats. These findings indicate that the effects of androgens on OT may be affected by the estrogen milieu, and elevated OT levels may be related to the blunting of appetite and prevention of obesity under estrogen-deficient conditions.

Emerging Treatments and Therapies for Autism Spectrum Disorder: A Narrative Review.

The prevalence of autism spectrum disorder (ASD) has increased over the last decade. In this regard, many emerging therapies have been described as ASD therapies. Although ASD does not have a cure, there are several management options available that can help reduce symptom severity. ASD is highly variable and, therefore, standard treatment protocols and studies are challenging to perform. Many of these therapies also address comorbidities for which patients with ASD have an increased risk. These concurrent diagnoses can include psychiatric and neurological disorders, including attention deficit and hyperactivity disorder, anxiety disorders, and epilepsy, as well as gastrointestinal symptoms such as chronic constipation and diarrhea. Both the extensive list of ASD-associated disorders and adverse effects from commonly prescribed medications for patients with ASD can impact presenting symptomatology. It is important to keep these potential interactions in mind when considering additional drug treatments or complementary therapies. This review addresses current literature involving novel pharmacological treatments such as oxytocin, bumetanide, acetylcholinesterase inhibitors, and memantine. It also discusses additional therapies such as diet intervention, acupuncture, music therapy, melatonin, and the use of technology to aid education. Notably, several of these therapies require more long-term research to determine efficacy in specific ASD groups within this patient population.

Vocal recognition of partners by female prairie voles.

Recognizing conspecifics is vitally important for differentiating kin, mates, offspring and social threats.1 Although often reliant upon chemical or visual cues, individual recognition across the animal kingdom is also facilitated by unique acoustic signatures in vocalizations.2-4 However, amongst the large Muroidea superfamily of rodents that encompasses laboratory species amenable to neurobiological studies, there is scant behavioral evidence for individual vocal recognition despite individual acoustic variation.5-10 Playback studies have found evidence for coarse communicative functions like mate attraction and territorial defense, but limited finer ability to discriminate known individuals' vocalizations.11-17 Such a capacity would be adaptive for species that form lifelong pair bonds requiring partner identification across timescales, distances and sensory modalities, so to improve the chance of finding individual vocal recognition in a Muroid rodent, we investigated vocal communication in the prairie vole (Microtus ochrogaster) - one of the few socially monogamous mammals.18 We found that the ultrasonic vocalizations of adult prairie voles can communicate individual identity. Even though the vocalizations of individual males change after cohabitating with a female to form a bond, acoustic variation across individuals is greater than within an individual so that vocalizations of different males in a common context are identifiable above chance. Critically, females behaviorally discriminate their partner's vocalizations over a stranger's, even if emitted to another stimulus female. These results establish the acoustic and behavioral foundation for individual vocal recognition in prairie voles, where neurobiological tools19-22 enable future studies revealing its causal neural mechanisms.

The interplay between borderline personality disorder and oxytocin: a systematic narrative review on possible contribution and treatment options.

Background: Borderline personality disorder (BPD) is a complex mental health condition marked by instability in mood, relationships, self-image, and behavior. Individuals with BPD often struggle with intense emotions, impulsivity, and maintaining stable relationships. Oxytocin, known as the "love hormone" or "bonding hormone," plays a crucial role in social bonding, trust, empathy, and emotional regulation and its dysregulation may contribute to BPD difficulties. This systematic review aims to analyze existing literature, examining the intricate interplay and encouraging future research and treatment strategies. Methods: A systematic search of Literature in PubMed, Embase and Psychinfo, without any language or time restriction, was performed until March 2024 combining thesaurus and free-search indexing terms related to "borderline personality disorder" and "oxytocin", producing 310 results (77 in PubMed, 166 in Embase and 67 in Psychinfo). Ninety-four full texts were analyzed, and 70 articles were included in qualitative analysis. Results: Oxytocin may influence attachment styles, parental behaviors, and stress responses, particularly in individuals with a history of childhood trauma. The interaction between oxytocin, genetics, early life experiences, and environmental factors contributes to the complexity of BPD. Genetic variations in the oxytocin receptor gene may influence social and emotional abilities and contribute to the development of psychopathology. Additionally, early adverse experiences, such as childhood maltreatment, can alter oxytocin functioning, impacting social cognition and emotional regulation.However, oxytocin's role in BPD treatment remains uncertain, with some studies suggesting potential benefits for specific symptoms like social threat avoidance, while others indicate adverse effects on nonverbal behavior and mentalizing. Conclusion: Understanding oxytocin's role in BPD offers insights into potential therapeutic interventions. While oxytocin-based treatments may hold promise for addressing specific symptoms, further research is needed.

Corrigendum: Effect of the nature of subsequent environment on oxytocin and cortisol secretion in maltreated children.

[This corrects the article DOI: 10.3389/fpsyt.2015.00173.].

Unlocking potential of oxytocin: improving intracranial lymphatic drainage for Alzheimer's disease treatment.

Background: The impediment to ß-amyloid (Aß) clearance caused by the invalid intracranial lymphatic drainage in Alzheimer's disease is pivotal to its pathogenesis, and finding reliable clinical available solutions to address this challenge remains elusive. Methods: The potential role and underlying mechanisms of intranasal oxytocin administration, an approved clinical intervention, in improving intracranial lymphatic drainage in middle-old-aged APP/PS1 mice were investigated by live mouse imaging, ASL/CEST-MRI scanning, in vivo two-photon imaging, immunofluorescence staining, ELISA, RT-qPCR, Western blotting, RNA-seq analysis, and cognitive behavioral tests. Results: Benefiting from multifaceted modulation of cerebral hemodynamics, aquaporin-4 polarization, meningeal lymphangiogenesis and transcriptional profiles, oxytocin administration normalized the structure and function of both the glymphatic and meningeal lymphatic systems severely impaired in middle-old-aged APP/PS1 mice. Consequently, this intervention facilitated the efficient drainage of Aß from the brain parenchyma to the cerebrospinal fluid and then to the deep cervical lymph nodes for efficient clearance, as well as improvements in cognitive deficits. Conclusion: This work broadens the underlying neuroprotective mechanisms and clinical applications of oxytocin medication, showcasing its promising therapeutic prospects in central nervous system diseases with intracranial lymphatic dysfunction.

Do pet dogs reciprocate the receipt of food from familiar and unfamiliar conspecifics?

Reciprocity is one of the most prominent explanations for the evolution of stable cooperation. Although reciprocity has been studied for decades in numerous animal species and behavioural contexts, its underlying proximate mechanisms remain unclear. Domestic dogs provide a useful model species for the study of proximate mechanisms, though there are currently inconsistent findings regarding dogs' propensity to reciprocate. Here, we investigated whether, after minimal training, pet dogs would press a button, which remotely controlled a food dispenser, to deliver food to an enclosure occupied by a helpful conspecific that had provided them with food or an unhelpful conspecific that had not provided them with food. We included an asocial control condition in which the enclosure was unoccupied and a social facilitation control in which the food delivery mechanism was non-functional. Whether subjects were familiar with the helpful and unhelpful conspecifics was also varied. In addition, to investigate potential mechanisms underlying reciprocity, we measured subjects salivary oxytocin concentration before and after they experienced the helpful and unhelpful acts. There was no effect of the previous helpfulness or the familiarity of the partner on the number of times subjects pressed the button. However, there was also no effect of the presence of a partner or the operationality of the food delivery mechanism on the number of button presses, indicating that subjects were not pressing the button to provision the partner. Moreover, the experience of the helpful or unhelpful act did not influence subjects' salivary oxytocin concentration. Variation in findings of reciprocity across studies appears to correspond with differing training protocols. Subjects' understanding of the task in the current study may have been constrained by the limited training received. Additional tests to verify subjects' understanding of such tasks are warranted in future studies.

Oxytocin does not acutely improve glucose tolerance in men with type 2 diabetes.

AIM: To assess oxytocin's acute glucoregulatory impact in men with type 2 diabetes in the context of our previous findings that oxytocin improves ß-cell responsivity in healthy men. METHODS: In a double-blind, crossover comparison, intranasal oxytocin (24 IU) and placebo, respectively, were administered to 25 fasted men with non-insulin-treated type 2 diabetes (age ± standard error of the mean, 63.40 ± 1.36 years; body mass index, 27.77 ± 0.66 kg/m2; HbA1c, 6.86% ± 0.08%; Homeostatic Model Assessment of Insulin Resistance (HOMA-IR, 3.44 ± 0.39) 60 minutes before an oral glucose tolerance test (oGTT). Key outcomes were compared with previous results in men with normal weight or obesity. RESULTS: Oxytocin compared with placebo increased plasma oxytocin concentrations and reduced the heart rate, but did not alter glucose metabolism in the 3 hours after oGTT onset (area under the curve, glucose, 2240 ± 80.5 vs. 2190 ± 69.5 mmol/L × min; insulin, 45 663 ± 4538 vs. 44 343 ± 4269 pmol/L × min; C-peptide, 235 ± 5.1 vs. 231 ± 15.9 nmol/L × min). CONCLUSIONS: This outcome contrasts with the oxytocin-induced attenuation of early postprandial glucose excursions in normal-weight individuals, but is in line with the absence of respective effects in men with obesity. We conclude that insulin resistance in type 2 diabetes is associated with decreased sensitivity to the acute glucoregulatory effect of oxytocin in male individuals.

Neuroendocrinology of bone.

The past decade has witnessed significant advances in our understanding of skeletal homeostasis and the mechanisms that mediate the loss of bone in primary and secondary osteoporosis. Recent breakthroughs have primarily emerged from identifying disease-causing mutations and phenocopying human bone disease in rodents. Notably, using genetically-modified rodent models, disrupting the reciprocal relationship with tropic pituitary hormone and effector hormones, we have learned that pituitary hormones have independent roles in skeletal physiology, beyond their effects exerted through target endocrine glands. The rise of follicle-stimulating hormone (FSH) in the late perimenopause may account, at least in part, for the rapid bone loss when estrogen is normal, while low thyroid-stimulating hormone (TSH) levels may contribute to the bone loss in thyrotoxicosis. Admittedly speculative, suppressed levels of adrenocorticotropic hormone (ACTH) may directly exacerbate bone loss in the setting of glucocorticoid-induced osteoporosis. Furthermore, beyond their established roles in reproduction and lactation, oxytocin and prolactin may affect intergenerational calcium transfer and therefore fetal skeletal mineralization, whereas elevated vasopressin levels in chronic hyponatremic states may increase the risk of bone loss.. Here, we discuss the interaction of each pituitary hormone in relation to its role in bone physiology and pathophysiology.

Temporalities of oxytocin for labour augmentation: a mixed-methods study of time factors shaping labour practices in a busy maternity unit in Tanzania.

BACKGROUND: High rates of labour augmentation with oxytocin have been found in some low- and lower-middle-income countries, causing potential perinatal harm. It is critical to understand the reasons for this overuse. Aim was to explore factors that shape practices around using oxytocin for labour augmentation in a high-volume labour ward in Dar es Salaam, Tanzania. METHODS: Mixed-methods data collection was conducted from March 2021 to February 2022, including structured observations of 234 births, 220 h of unstructured labour ward observations and 13 individual in-depth interviews with birth attendants. Thematic network analysis and descriptive statistics were used to analyse data. We used a time-lens to understand practices of oxytocin for labour augmentation in time-pressured labour wards. RESULTS: Birth attendants constantly had to prioritise certain care practices over others in response to time pressure. This led to overuse of oxytocin for augmentation to ensure faster labour progression and decongestion of the, often overburdened, ward. Simultaneously, birth attendants had little time to monitor foetal and maternal condition. Surprisingly, while oxytocin was used in 146 out of 234 (62.4%) structured labour observations, only 9/234 (4.2%) women had active labour lasting more than 12 h. Correspondingly, 21/48 (43.8%) women who were augmented with oxytocin in the first stage of labour had uncomplicated labour progression at the start of augmentation. While the partograph was often not used for decision-making, timing of starting oxytocin often correlated with natural cycles of ward-rounds and shift-turnovers instead of individual women's labour progression. This resulted in co-existence of 'too early' and 'too late' use of oxytocin. Liberal use of oxytocin for labour augmentation was facilitated by an underlying fear of prolonged labour and low alertness of oxytocin-related risks. CONCLUSIONS: Time scarcity in the labour ward often made birth attendants deviate from clinical guidelines for labour augmentation with oxytocin. Efforts to navigate time pressure resulted in too many women with uncomplicated labour progression receiving oxytocin with little monitoring of labour. Fear of prolonged labour and low alertness to oxytocin-mediated risks were crucial drivers. These findings call for research into safety and benefits of oxytocin in low-resource settings and interventions to address congestion in labour wards to prevent using oxytocin as a time-management tool.

Developmental effects of oxytocin on GABAergic neurons in the olfactory brain regions.

Oxytocin affects social recognition, interactions, and behavior in adults. Despite growing data on the role of oxytocin in the sensory systems, its effects on early olfactory system development remain poorly understood. The present study aimed to investigate the developmental impact of oxytocin on selected parameters of the GABAergic system in olfactory brain regions. We found a significant increase in the expression of GABAergic markers and scaffolding proteins in the olfactory bulb during the early stages of development in both male and female rats, regardless of oxytocin treatment administered on postnatal days 2 and 3 (P2 and P3, 5 µg/pup). Oxytocin administration markedly reduced the expression of the scaffolding protein Gephyrin in male rats and it led to a significant increase in the number of GABAergic synaptic puncta in the piriform cortex of male rats at P5, P7, and P9. Our data suggest that the developmental action of oxytocin in relation to the GABAergic system may represent a mechanism by which the plasticity and maturation of olfactory brain regions are regulated.