Showing papers on "Oxytocin published in 2012"

Oxytocin stimulates adult neurogenesis even under conditions of stress and elevated glucocorticoids.

Abstract: Oxytocin has been linked to social behavior, including social recognition, pair bonding and parenting, but its potential role in promoting neuronal growth has not been investigated. We show here that oxytocin, but not vasopressin, stimulates both cell proliferation and adult neurogenesis in the hippocampus of rats. Oxytocin is also capable of stimulating adult neurogenesis in rats subjected to glucocorticoid administration or cold water swim stress. These findings suggest that oxytocin stimulates neuronal growth and may protect against the suppressive effects of stress hormones on hippocampal plasticity.

Peripheral oxytocin suppresses food intake and causes weight loss in diet-induced obese rats

Abstract: Growing evidence suggests that oxytocin plays an important role in the regulation of energy balance and that central oxytocin administration induces weight loss in diet-induced obese (DIO) animals....

Cortisol-induced increases of plasma oxytocin levels predict decreased immediate free recall of unpleasant words

Abstract: Cortisol and oxytocin have been shown to interact in both the regulation of stress responses and in memory function. In the present study we administered cortisol to 35 healthy female subjects in a within-subject double-blind placebo-controlled design, while measuring oxytocin levels, adrenocorticotropic hormone (ACTH) levels, and free recall of pleasant and of unpleasant words. We found that cortisol administration suppressed ACTH levels and (1) induced a decrease in oxytocin associated with ACTH suppression and (2) an increase in oxytocin that was independent from ACTH suppression. This cortisol-induced increase in plasma oxytocin was associated with a selective decrease in immediate free recall of unpleasant words from primacy positions. The present results add to evidence that cortisol-induced increases in oxytocin could mediate some of the effects of stress and cortisol on memory, and possibly play a role in the regulation of the hypothalamo-pituitary–adrenal stress response. This mechanism could significantly impact affective and social behaviors, in particular during times of stress.

An obligate role of oxytocin neurons in diet induced energy expenditure.

Abstract: Oxytocin neurons represent one of the major subsets of neurons in the paraventricular hypothalamus (PVH), a critical brain region for energy homeostasis. Despite substantial evidence supporting a role of oxytocin in body weight regulation, it remains controversial whether oxytocin neurons directly regulate body weight homeostasis, feeding or energy expenditure. Pharmacologic doses of oxytocin suppress feeding through a proposed melanocortin responsive projection from the PVH to the hindbrain. In contrast, deficiency in oxytocin or its receptor leads to reduced energy expenditure without feeding abnormalities. To test the physiological function of oxytocin neurons, we specifically ablated oxytocin neurons in adult mice. Our results show that oxytocin neuron ablation in adult animals has no effect on body weight, food intake or energy expenditure on a regular diet. Interestingly, male mice lacking oxytocin neurons are more sensitive to high fat diet-induced obesity due solely to reduced energy expenditure. In addition, despite a normal food intake, these mice exhibit a blunted food intake response to leptin administration. Thus, our study suggests that oxytocin neurons are required to resist the obesity associated with a high fat diet; but their role in feeding is permissive and can be compensated for by redundant pathways.

Elevated Salivary Levels of Oxytocin Persist More than 7 h after Intranasal Administration

Abstract: We addressed the question how long salivary oxytocin levels remain elevated after intranasal administration, and whether it makes a difference when 16 IU or 24 IU of oxytocin administration is used. Oxytocin levels were measured in saliva samples collected from 46 female participants right before intranasal administration (at 9:30 AM) of 16 IU (n = 18) or 24 IU (n = 10) of oxytocin, or a placebo (n = 18), and each hour after administration, for 7h in total. Oxytocin levels did not differ among conditions before use of the nasal spray. Salivary oxytocin levels in the placebo group showed high stability across the day. After oxytocin administration oxytocin levels markedly increased, they peaked around 1h after administration, and were still significantly elevated 7h after administration. The amount of oxytocin (16 IU or 24 IU) did not make a difference for oxytocin levels. The increase of oxytocin levels for at least 7h shows how effective intranasal administration of oxytocin is. Our findings may raise ethical questions about potentially persisting behavioral effects after participants have left the lab setting. More research into the long-term neurological and behavioral effects of sniffs of oxytocin is urgently needed.

Roles of Oxytocin Neurones in the Control of Stress, Energy Metabolism, and Social Behaviour

Abstract: Oxytocin neurones are activated by stressful stimuli, food intake and social attachment. Activation of oxytocin neurones in response to stressful stimuli or food intake is mediated, at least in part, by noradrenaline/prolactin-releasing peptide (PrRP) neurones in the nucleus tractus solitarius, whereas oxytocin neurones are activated after social stimuli via medial amygdala neurones. Activation of oxytocin neurones induces the release of oxytocin not only from their axon terminals, but also from their dendrites. Oxytocin acts locally where released or diffuses and acts on remote oxytocin receptors widely distributed within the brain, resulting in anxiolytic, anorexic and pro-social actions. The action sites of oxytocin appear to be multiple. Oxytocin shows anxiolytic actions, at least in part, via serotoninergic neurones in the median raphe nucleus, has anorexic actions via pro-opiomelanocortin neurones in the nucleus tractus solitarius and facilitates social recognition via the medial amygdala. Stress, obesity and social isolation are major risk factors for mortality in humans. Thus, the oxytocin-oxytocin receptor system is a therapeutic target for the promotion of human health.

Central administration of oxytocin receptor ligands affects cued fear extinction in rats and mice in a timepoint-dependent manner

Abstract: Rationale Oxytocin (OXT) has been proposed as a potential therapeutic agent for post-traumatic stress disorder (PTSD).

The influence of oxytocin administration on responses to infant faces and potential moderation by OXTR genotype

Abstract: Oxytocin is a neuropeptide that is associated with increases in social affiliative behaviors, particularly toward infants. However, no previous study has investigated healthy adults’ responses to infant faces following oxytocin administration. In addition, given that preliminary evidence suggests that a single-nucleotide polymorphism of the oxytocin receptor (OXTR) gene, rs53576, may influence behaviors associated with parental sensitivity, we assessed whether such responses vary according to OXTR rs53576 genotype. The present study assessed the effects of intranasally administered oxytocin and OXTR genotype on human adults’ preferences for infant faces. A double-blind, between-groups design was used, with 57 genotyped volunteers randomly assigned to receive intranasally administered oxytocin or placebo. Fifty minutes following the administration of oxytocin or placebo, participants viewed infants’ and adults’ faces showing neutral expressions and assessed how appealing they found each face. Infants’ faces were more strongly preferred following oxytocin inhalation relative to placebo. When participants were separated according to genotype, this effect was only observed for participants homozygous for the rs53576G allele. Parallel effects were not seen for adults’ faces. The present results are consistent with the hypothesis that acute oxytocin administration increases sensitivity to reward-relevant features of infants and/or reduces sensitivity to their aversive properties. The results are also consistent with suggestions of more efficient oxytocinergic function in rs53576G homozygotes.

Neuroendocrine and behavioural responses to exposure to an infant in male prairie voles.

Abstract: Paternal behaviour and pair-bond formation are defining characteristics of social monogamy. However, in comparison to pair-bonding, the endocrine factors associated with the male care of young are not well studied. In the present study, plasma concentrations of oxytocin, vasopressin and corticosterone (CORT) were measured in reproductively naive male prairie voles as a function of exposure to an infant or control manipulations (i.e. handling or exposure to a wooden dowel). Plasma oxytocin concentrations were transiently elevated within 10 min of pup exposure. Although plasma CORT concentration typically increases after handling, after 10 min of pup exposure, the concentration of plasma CORT was not increased, suggesting an attenuation of CORT release by pup exposure. Group differences in the concentrations of plasma hormones were no longer detected at 20 or 60 min after treatment. These patterns of rapid change in the concentrations of plasma oxytocin and CORT were observed in both juvenile and adult males but not detected after control procedures. Plasma vasopressin, assessed only in adult males, did not vary as a function of pup exposure or other manipulations. In the paraventricular nucleus of the hypothalamus, pup exposure also increased activation (as assessed by the measurement of c-Fos) of neurones that stained for either oxytocin or vasopressin, whereas it decreased c-Fos expression in neurones stained for corticotrophin-releasing hormone. In addition, brief pup exposure (20 min) facilitated subsequent partner preference formation when alloparental males and pup attackers were considered as a group. In the context of other studies, these data support the hypothesis that neuroendocrine changes associated with male alloparental behaviour are related to those implicated in pair-bonding.

Modulation of anxiety behavior in the elevated plus maze using peptidic oxytocin and vasopressin receptor ligands in the rat.

Abstract: Oxytocin (OT) and arginine vasopressin (AVP), in their capacities as neuromodulators, are believed to play an important role in mood control, including regulation of the anxiety response. In the present study, the contributions of oxytocin and vasopressin receptor modulation to anxiety-like behaviors were examined in male Sprague-Dawley rats. The behavioral effects of the OT receptor agonist, carbetocin (intracerebroventricular, intravenous and intraperitoneal routes), the AVP receptor agonist desmopressin (intravenous route), and the OT/AVP(1A) receptor antagonist atosiban (intravenous route) were evaluated in the elevated plus maze. The benzodiazepine diazepam was included as a positive control. Central but not systemic administration of carbetocin produced pronounced anxiolytic-like behavioral changes comparable to those measured following systemic diazepam treatment. The anxiolytic efficacy of carbetocin was maintained following 10 days of once-daily treatment, contrasting with the effects of diazepam which were no longer distinguishable from saline treatment. Systemic administration of desmopressin produced anxiogenic-like effects whereas systemic atosiban produced anxiolytic-like effects. Co-administration of desmopressin with atosiban resulted in saline-like behavioral responses, implicating an AVP(1A) receptor mechanism in the anxiolytic and anxiogenic effects of these neuropeptides following systemic administration. A peripherally-mediated antidiuretic effect of desmopressin on water consumption was also demonstrated. These results highlight the potential therapeutic utility of AVP(1A) receptor blockade in the modulation of anxiety-related behaviors; AVP(1A) receptor blockade appears to be a more promising pharmacological target than does OT receptor activation following systemic drug administration.

Maternal contact differentially modulates central and peripheral oxytocin in rat pups during a brief regime of mother-pup interaction that induces a filial huddling preference.

Abstract: Central oxytocin mediates the acquisition of a filial preference for maternal odour in rat pups, manifested by their huddling preferences. The present study was designed to examine whether maternal care modulates oxytocin concentrations in rat pups and, if so, how different types of maternal contact are associated with the pups' oxytocin concentrations. Pairs of 14-day-old littermates were removed from their home cage for 1 h and then placed with a lactating foster mother for 2 h, or they remained isolated at room temperature. Enzyme immunoassays revealed that maternal care and maternal separation can differentially modulate pups' oxytocin concentrations. Both hypothalamic and serum oxytocin increased during the 1-h separation. Pups placed with a foster mother after the separation maintained the same concentrations in the hypothalamus and serum through the fostering period. By contrast, pups placed with no mother showed a further increase in hypothalamic oxytocin but serum oxytocin decreased. Behavioural analyses revealed that skin-to-skin contact with the mother, but not simple physical contact or maternal licking/grooming, was positively correlated with the pups' hypothalamic oxytocin concentrations. These neuroendocrine data match previous findings showing that skin-to-skin contact with mother facilitates the acquisition of the pups' huddling preference for a maternally-associated odour. Taken together, the present study suggests that maternal skin-to-skin contact stimulates pups' central oxytocin, at the same time as creating the conditions for inducing a preference for maternal odour and establishing a social affiliation in rat pups; the natural schedule of maternal separation and reunion may modulate pups' oxytocin concentrations, providing scaffolding for the acquisition of their filial huddling preference.

Differential contribution of hypothalamic MAPK activity to anxiety-like behaviour in virgin and lactating rats.

Abstract: The c-Raf – MEK1/2 – ERK1/2 mitogen-activated protein kinase (MAPK) intracellular signalling cascade in neurons plays important roles in the control of a variety of behaviours, including social behaviours and anxiety. These roles partially overlap with those described for oxytocin (OXT), and it has been shown that OXT activates the MAPK pathway in the hypothalamus (of male), and hippocampus (of female) rats. Here, by combining behavioural (light/dark box) and biochemical analyses (western blotting), we tested two hypotheses: (i) that OXT is anxiolytic within the hypothalamus of females, and (ii) that this effect, as well as that of lactation-associated anxiolysis, depends on the recruitment of the MAPK pathway. We found that, when injected bilaterally into the hypothalamic paraventricular nucleus (PVN), OXT decreased anxiety-like behaviour in virgins, and that this effect depended on phosphorylation of MEK1/2. MAPK pathway activation in lactation was evident by high phosphorylated (p) MEK1/2 levels, and nuclear translocation of ERK1. The high pMEK1/2 levels were necessary for the anxiolytic phenotype typically observed during lactation. Interestingly, exogenous OXT in lactating rats reduced pMEK1/2 levels without a concomitant effect on anxiety, indicating that OXT receptor activation can lead to recruitment of additional intracellular pathways to modulate MEK activity. Still other pathways could include MEK, but without subsequent activation of ERK, as we did not observe any increase in OXT-induced ERK phosphorylation. Together the results demonstrate that the MAPK pathway, especially MEK1/2, is critically involved in the regulation of anxiety-like behaviour in female rats.

Newborn feeding behaviour depressed by intrapartum oxytocin: a pilot study.

Abstract: Aim: To investigate the effect intrapartum oxytocin administration can have on Primitive Neonatal Reflexes. The secondary objective was to observe the influence of intrapartum oxytocin may have on breastfeeding. Methods: Twenty healthy primiparae with a single gestation at term were included. To assess Primitive Neonatal Reflexes, video film was taken during an experimental situation designed to elicit Primitive Neonatal Reflexes. Three independent observers blinded to the oxytocin dose that had been administered coded the Primitive Neonatal Reflexes. Data regarding breastfeeding were collected by telephone at 3 months. Results: Medium oxytocin dose was 1931.9 ± 1754.4 mUI. A Kappa index >0.75 was obtained for four Primitive Neonatal Reflexes: swallow, jaw jerk, suck and gazing. A negative association was found between oxytocin dose and sucking (p = 0.03). At 3 months of life, women exclusively breastfeeding (63.1%) had received a significantly lower average dose of oxytocin than those not exclusively breastfeeding (36.8%) (p = 0.04). Conclusion: In this pilot study, intrapartum exogenous oxytocin seems to disturb sucking and breastfeeding duration. Further studies are required to confirm these results and to ascertain whether there could be other effects of intrapartum oxytocin on newborn behaviour.