Oxytocin Receptor mRNA Research Articles

Maternal High Fat Diet-Induced Obesity Modifies Histone Binding and Expression of Oxtr in Offspring Hippocampus in a Sex-Specific Manner.

Maternal obesity during pregnancy increases risk for neurodevelopmental disorders in offspring, although the underlying mechanisms remain unclear. Epigenetic deregulation associates with many neurodevelopmental disorders, and recent evidence indicates that maternal nutritional status can alter chromatin marks in the offspring brain. Thus, maternal obesity may disrupt epigenetic regulation of gene expression during offspring neurodevelopment. Using a C57BL/6 mouse model, we investigated whether maternal high fat diet (mHFD)-induced obesity alters the expression of genes previously implicated in the etiology of neurodevelopmental disorders within the Gestational Day 17.5 (GD 17.5) offspring hippocampus. We found significant two-fold upregulation of oxytocin receptor (Oxtr) mRNA in the hippocampus of male, but not female, GD 17.5 offspring from mHFD-induced obese dams (p < 0.05). To determine whether altered histone binding at the Oxtr gene promoter may underpin these transcriptional changes, we then performed chromatin immunoprecipitation (ChIP). Consistent with the Oxtr transcriptional changes, we observed increased binding of active histone mark H3K9Ac at the Oxtr transcriptional start site (TSS) in the hippocampus of mHFD male (p < 0.05), but not female, offspring. Together, these data indicate an increased vulnerability of male offspring to maternal obesity-induced changes in chromatin remodeling processes that regulate gene expression in the developing hippocampus, and contributes to our understanding of how early life nutrition affects the offspring brain epigenome.

Central relaxin-3 receptor (RXFP3) activation impairs social recognition and modulates ERK-phosphorylation in specific GABAergic amygdala neurons.

In mammals, the extended amygdala is a neural hub for social and emotional information processing. In the rat, the extended amygdala receives inhibitory GABAergic projections from the nucleus incertus (NI) in the pontine tegmentum. NI neurons produce the neuropeptide relaxin-3, which acts via the Gi/o-protein-coupled receptor, RXFP3. A putative role for RXFP3 signalling in regulating social interaction was investigated by assessing the effect of intracerebroventricular infusion of the RXFP3 agonist, RXFP3-A2, on performance in the 3-chamber social interaction paradigm. Central RXFP3-A2, but not vehicle, infusion, disrupted the capacity to discriminate between a familiar and novel conspecific subject, but did not alter differentiation between a conspecific and an inanimate object. Subsequent studies revealed that agonist-infused rats displayed increased phosphoERK(pERK)-immunoreactivity in specific amygdaloid nuclei at 20min post-infusion, with levels similar to control again after 90min. In parallel, we used immunoblotting to profile ERK phosphorylation dynamics in whole amygdala after RXFP3-A2 treatment; and multiplex histochemical labelling techniques to reveal that after RXFP3-A2 infusion and social interaction, pERK-immunopositive neurons in amygdala expressed vesicular GABA-transporter mRNA and displayed differential profiles of RXFP3 and oxytocin receptor mRNA. Overall, these findings demonstrate that central relaxin-3/RXFP3 signalling can modulate social recognition in rats via effects within the amygdala and likely interactions with GABA and oxytocin signalling.

Long-Term Isolation Elicits Depression and Anxiety-Related Behaviors by Reducing Oxytocin-Induced GABAergic Transmission in Central Amygdala.

Isolation stress is a major risk factor for neuropsychiatric disorders such as depressive and anxiety disorders. However, the molecular mechanisms underlying isolation-induced neuropsychiatric disorders remain elusive. In the present study, we investigated the subcellular mechanisms by which long-term isolation elicits depression and anxiety-related behaviors in mice. First, we found that long-term isolation induced depression-related behaviors in the forced swimming test (FST) and the sucrose preference test, as well as anxiety-related behaviors in the elevated zero maze test (EZMT) and the open field test. Next, we showed that intracentral amygdala (CeA) injection of oxytocin (OXT), but not intracerebroventricular injection, attenuated isolation-induced depression and anxiety-related behaviors via oxytocin receptor (OXTR), not vasopressin-1a receptor (V1aR), in the FST and EZMT, respectively. Quantitative real-time polymerase chain reaction analysis revealed that after 5 weeks of isolation, mRNA transcription of OXTR in the CeA, but not that of V1aR, significantly decreased, whereas OXT and vasopressin mRNA transcription in the paraventricular nucleus of hypothalamus did not change significantly. Whole-cell patch clamping of acute brain slices demonstrated that the frequency of miniature inhibitory postsynaptic currents (mIPSCs) in CeA neurons, but not their amplitude, was lower in isolated mice than in group-housed mice. Notably, OXT treatment increased the mIPSC frequency in the CeA neurons, but to a lesser extent in the case of isolated mice than in that of group-housed mice via OXTR. Taken together, our findings suggest that long-term isolation down-regulates OXTR mRNA transcription and diminishes OXT-induced inhibitory synaptic transmission in the CeA and may contribute to the development of depression and anxiety-related behaviors in isolated mice through the enhancement of CeA activity.

Oxytocin receptor mRNA expression in dorsolateral prefrontal cortex in major psychiatric disorders: A human post-mortem study

There is growing interest in oxytocin as a putative treatment for various psychiatric disorders including major depressive disorder, bipolar disorder and schizophrenia/schizoaffective disorder. However, potential alterations in the endogenous brain oxytocin system in these disorders are poorly characterized. Brain expression of oxytocin and its receptor genes in patients with these psychiatric disorders has not been well studied outside the hypothalamus. We measured expression of mRNA for oxytocin and its receptor in the dorsolateral prefrontal cortex of postmortem brains using quantitative polymerase chain reaction in a total of 581 individuals. These individuals either were diagnosed with major depressive disorder (n = 135), bipolar disorder (n = 57), schizophrenia/schizoaffective disorder (n = 169), or were control subjects, defined as individuals with no lifetime history of any of these disorders (n = 220). Diagnoses of major depressive disorder and bipolar disorder were associated with significantly increased oxytocin receptor mRNA levels in the dorsolateral prefrontal cortex. This finding is discussed in light of the extant literature on the dysregulation of oxytocin signaling in individuals with major psychiatric disorders.

Adolescent intermittent ethanol exposure: Effects on pubertal development, novelty seeking, and social interaction in adulthood

Alcohol use initiated early in adolescence is a major predictor for the development of alcohol use disorders. This risk may be increased when drinking is initiated around the time of puberty, given evidence of bidirectional relationships between alcohol and gonadal hormones. The current study examined the effects of adolescent intermittent ethanol exposure (AIE) on pubertal timing and expression of novelty-seeking and peer-directed behaviors as well as neural correlates of these behaviors. AIE did not affect pubertal timing or the later expression of novelty-seeking and peer-directed behaviors. AIE increased corticosterone (CORT) levels in females not tested behaviorally in adulthood or tested in the novel-object exploration paradigm, whereas social interaction blunted CORT levels in AIE females. Delays in pubertal timing and decreases in CORT levels were correlated, however, with increased novelty seeking in adult males - a phenotype associated with increased addiction vulnerability. In females, social testing elevated oxytocin receptor (OXTR) mRNA expression in the central amygdala (CeA), with this social testing-associated elevation evident in the lateral septum (LS), regardless of sex. Vasopressin receptor 1a (AVP-1aR) mRNA expression in the CeA was enhanced by social testing in females, but not males, with expression of this gene suppressed by social testing in the LS in males, but not females. Together, these data demonstrate that behavioral and neural alterations that may serve as risk factors in later drug vulnerabilities are likely not the result of a single insult, but may reflect interactions among several variables including sex, pubertal timing, stress reactivity, and test circumstances.

Parent-offspring cohabitation after weaning inhibits partner preference and alters central oxytocin and dopamine systems in adult mandarin vole.

In some mammals, offspring may live with their parents for a very long time after weaning, but little is known about the effect of post-weaning parent-offspring cohabitation on the behavioral and neurobiological development of offspring. Here, we explored the effect of this experience on partner preference in adult mandarin vole (Microtus mandarinus). Levels of central oxytocin (OT), tyrosine hydroxylase (TH), as well as OT receptor (OTR), dopamine D1-type and D2-type receptors (D1R and D2R) mRNA expression in the nucleus accumbens (NAcc) and medial amygdala (MeA) were also measured. Our data showed that post-weaning living with parents inhibited the preference to partner over an unfamiliar opposite-sex conspecific. Voles with this experience possessed more OT-but less TH-immunoreactive neurons as compared to the control. Additionally, males with this experience had less D2R and OTR mRNA expression in the NAcc than the control while females had less D2R mRNA expression in the NAcc, but more OTR mRNA expression in the MeA. These findings demonstrate that post-weaning parent-offspring cohabitation inhibits the partner preference formation at adulthood, and these changes may be associated with alterations in the levels of central OT and DA, and their receptor mRNA expression in specific brain regions.

Oxytocin administration in the basolateral and central nuclei of amygdala moderately suppresses food intake.

Oxytocin (OT) at acting central nuclei decreases meal size and reduces intake of palatable sweet solutions. It remains largely unclear as to which brain sites mediate OT's effect on palatability versus energy or the combination of those aspects of consumption. Here, we expanded the search for sites that mediate anorexigenic properties of OT by focusing on two subdivisions of the amygdala, its central (CNA) and basolateral (BLA) nuclei. We injected OT directly into the BLA or CNA in rats and assessed intake of standard chow induced by energy deprivation and intake of sweet solutions in nondeprived animals. We examined whether these effects are reversible by OT receptor (OTr) antagonism and whether OT presence in BLA or CNA induces taste aversion. We also determined the effect of energy deprivation and exposure to sweet saccharin on BLA and CNA expression of OTr mRNA. OT administration in BLA at 0.3 μg and in CNA at 1 μg reduced standard chow intake after deprivation by ~25%. Only administration of OT in BLA was effective in suppressing consumption of sucrose and saccharin solutions. The anorexigenic effects of OT in BLA and CNA were attenuated by OTr antagonist, L-368,899, pretreatment. OT at anorexigenic doses did not promote acquisition of taste aversion. BLA OTr mRNA expression was affected by exposure to palatable saccharin, whereas that of CNA OTr, by energy deprivation. OT in the amygdala moderately decreases food intake. The functional relationship between amygdalar OT and energy intake versus palatability-driven intake depends on the discrete localization of the OTr within this complex structure.

Chronic central oxytocin infusion impairs sociability in mandarin voles

Oxytocin (OT) has been reported to increase social contact, however some studies have related OT to reduced social contact, particularly with unfamiliar individuals. The underlying mechanisms of OT on social contact remain unclear. In this study, male mandarin vole (Microtus mandarinus), a socially monogamous rodent, was used as an animal model in which osmotic minipumps were used to intracerebroventricularly administer two dosages of OT or saline for 12 consecutive days. We examined the effect of long-term OT treatment on social behavior, anxiety levels, and levels of oxytocin, vasopressin (AVP) and dopamine (DA) receptors mRNA expression in the nucleus accumbens (NAcc), and medial amygdala (MeA). The data showed that chronic central OT infusion decreased social preference behavior (a reduction of preference for interacting with novel social stimulus relative to a novel object) concomitant to a reduction of OT receptors in the NAcc and MeA. We also found alterations in AVP and DA receptor levels in the NAcc and MeA after treatment with OT. Moreover, chronic central OT treatment did not affect levels of anxiety-related behavior in male voles. In conclusion, these results indicated that chronic OT treatment may differ from the treatment effects predicted in short-term studies, and significant dosage effects were observed.

Effect of alcohol use disorder on oxytocin peptide and receptor mRNA expression in human brain: A post-mortem case-control study

Animal and human evidence supports a role for oxytocin in alcohol-seeking behaviors. There is interest, therefore, in targeting the oxytocin pathway as a new pharmacologic approach to treat alcohol use disorder. To this end, it is important to understand the effect of alcohol use disorder on endogenous oxytocin in brain regions that are relevant for the initiation and maintenance of alcohol use disorder. We examined human post-mortem brain tissue from males with alcohol use disorder (n=11) compared to nonalcohol dependent male controls (n=16). We a priori targeted five brain regions that in rodent studies, are projection areas for oxytocin neurons: nucleus accumbens, amygdala, hippocampus, ventral tegmental area and prefrontal cortex. Fold change in mRNA levels of oxytocin peptide and receptor were measured in each of the brain regions studied. Fold change for oxytocin peptide mRNA was significantly elevated in the prefrontal cortex of subjects with alcohol use disorder compared to controls (uncorrected p=0.0001; FDR-corrected p=0.001). For the entire sample of 27 subjects, there was a significant positive correlation between the fold change in oxytocin peptide mRNA in the prefrontal cortex and both daily alcohol intake (r2=0.38; p=0.002) and drinks per week (r2=0.24; p=0.02). Results are discussed in light of the previous animal and human literature on changes in the endogenous oxytocin system as an effect of chronic alcohol exposure.

The regulation of oxytocin and oxytocin receptor in human placenta according to gestational age

Oxytocin (OXT) is a peptide hormone that plays a central role in the regulation of parturition and lactation. OXT signaling is mediated by OXT receptor (OXTR), which shows species- and tissue-specific expressions and gene regulation. In the present study, we examined the synthesis of OXT and OXTR in human placenta tissue according to gestational age. A total of 48 placentas were divided into early preterm, late preterm and term groups depending on gestational age, and expression of OXT and OXTR was evaluated. First, OXT and OXTR mRNA and protein were detected in normal placenta tissue via Q-PCR, Dot-blot and Western blot assay. Both OXT and OXTR levels in normal placenta increased gradually in the late stage of pregnancy, suggesting that local OXT may play a critical role in the function of the placenta. To determine the regulatory mechanism of OXT, placental BeWo cells were administrated estrogen (E2) or progesterone (P4), and expression of OXT and OXTR was tested. The mRNA and protein levels of OXT and OXTR were upregulated by E2 but blocked by co-treatment with P4 In order to confirm the estrogen receptor (ESR)-mediated signaling, we administrated ESR antagonists together with E2 to BeWo cells. As a result, both OXT and OXTR were significantly altered by ESR1 antagonist (MPP) while moderately regulated by ESR2 antagonist (PHTPP). These results suggest that OXT and OXTR are controlled mainly by E2 in the placenta via ESR1 and thus may play physiological functions in the human placenta during the late stage of pregnancy.

Up-regulation of oxytocin receptor gene and protein in the sheep anterior pituitary by a dopamine derivative (salsolinol)

Specific oxytocin receptors (OTR) have been identified in the anterior pituitary (AP), and their expression has been shown to change in relation to the animal physiological stage, whereas salsolinol (a derivative of dopamine) has been shown to stimulate the synthesis and release of oxytocin (OT) in lactating sheep. In the present study, the expression of both OTR mRNA and OTR protein in the AP were examined by real-time quantitative PCR and enzyme-linked immunosorbent assay, either in anestrous or lactating sheep 48 h after weaning lambs. Moreover, the effect of salsolinol administered via an intracerebroventricular (i.c.v.) infusion was tested in additional sheep at the same physiological stages. The i.c.v. infusions of Ringer-Locke (control) and salsolinol solutions were carried out from 10:00 to 15:00 h in a serial manner, i.e. five 30-min infusions at 30-min intervals. We observed both OTR gene and OTR protein expression in the AP, in both anestrous and lactating sheep, but it was significantly (P &amp;lt; 0.01 and P &amp;lt; 0.05, respectively) higher in the AP of lactating animals compared to anestrous animals. Salsolinol i.c.v. treatment in anestrous sheep evoked a significant (P &amp;lt; 0.05) increase in both OTR gene and OTR protein expression compared to control animals. In contrast, salsolinol did not affect either OTR gene or OTR protein expression in lactating sheep. In conclusion, the expression of OTR in the sheep AP is upregulated by salsolinol. The effect of salsolinol was more pronounced in non-lactating sheep, with a reduced response due to ongoing OTR expression in lactating animals. Increased expression of OTR in the AP of lactating sheep may be related to the stimulation of pituitary lactotrophs by OT following the release of prolactin during suckling.

Relative expression of oxytocin receptor gene in buffalo endometrium in late luteal phase and pregnancy stages

ABSTRACTMolecular level information related to buffalo (Bubalus bubalis) reproduction and related genes is not present at appropriate level. If such exploration is made in the form of comparison between expression of genes is made between non-pregnant and pregnant phase, it may be helpful to aid manipulate the reproduction. Hence, the present study was carried out to reveal mRNA quantitative real time expression of oxytocin receptor (OTR) mRNA. IFN-τ is considered as the substance of maternal recognition of pregnancy and shut down the probable mechanisms which lead to luteolysis. Such mechanism includes shutting down of OTR. Therefore, relative expression of OTR was studied in endometrial tissue of three groups. The groups were non-pregnant late luteal phase, pregnancy stage I (pregnancy of <42 days) and pregnancy stage II (>42 days of pregnancy). With designed primer and GAPDH as house-keeping gene, relative mRNA expression was measured in Real-time PCR. After statistical analysis of results, the gene found to be expressed in all three stages with non-significant difference.

The expression of genes involved in myometrial contractility changes during ex situ culture of pregnant human uterine smooth muscle tissue.

Background: Ex situ analyses of human myometrial tissue has been used to investigate the regulation of uterine quiescence and transition to a contractile phenotype. Following concerns about the validity of cultured primary cells, we examined whether myometrial tissue undergoes culture-induced changes ex situ that may affect the validity of in vitro models. Objectives: To determine whether human myometrial tissue undergoes culture-induced changes ex situ in Estrogen receptor 1 (ESR1), Prostaglandin-endoperoxide synthase 2 (PTGS2) and Oxytocin receptor (OXTR) expression. Additionally, to determine whether culture conditions approaching the in vivo environment influence the expression of these key genes. Methods: Term non-laboring human myometrial tissues were cultured in the presence of specific treatments, including; serum supplementation, progesterone and estrogen, cAMP, PMA, stretch or NF-κB inhibitors. ESR1, PTGS2 and OXTR mRNA abundance after 48 h culture was determined using quantitative RT-PCR. Results: Myometrial tissue in culture exhibited culture-induced up-regulation of ESR1 and PTGS2 and down-regulation of OXTR mRNA expression. Progesterone prevented culture-induced increase in ESR1 expression. Estrogen further up-regulated PTGS2 expression. Stretch had no direct effect, but blocked the effects of progesterone and estrogen on ESR1 and PTGS2 expression. cAMP had no effect whereas PMA further up-regulated PTGS2 expression and prevented decline of OXTR expression. Conclusion: Human myometrial tissue in culture undergoes culture-induced gene expression changes consistent with transition toward a laboring phenotype. Changes in ESR1, PTGS2 and OXTR expression could not be controlled simultaneously. Until optimal culture conditions are determined, results of in vitro experiments with myometrial tissues should be interpreted with caution.

Oxytocin receptors in dioestrous and anoestrous canine uteri.

The aim of the study was to localize oxytocin receptors (OTR) and measure mRNA expression of OTR in the canine uterus with and without the influence of progesterone. Uterine samples were taken from nine anoestrous and eight dioestrous bitches during ovariohysterectomy. Histological changes were evaluated in haematoxylin and eosin (HE)-stained samples. Purified polyclonal antibody for OTR was used in immunohistochemistry to localize receptors in uterine layers. Relative mRNA concentration of OTR was evaluated with real-time PCR from full-thickness uterine samples taken from the middle horn and the body. Myometrial smooth muscle cells, endometrial luminal epithelium (LE) and deep and superficial glandular epithelium were positively stained for oxytocin receptors in non-pregnant animals. No significant difference in staining intensity was detected between uterine middle horn and body. However, the staining intensity of LE was significantly higher in dioestrous than in anoestrous uteri (p<.05). Leucocytes and endothelium of blood vessels were also positively stained for OTR. Real-time PCR showed no significant differences in OTR mRNA expression between the middle horn and the body of the uterus, or between anoestrous and dioestrous uterus. No correlation was noted between OTR mRNA expression and blood progesterone concentration. In conclusion, despite the apparent inactivity, the uterus of the non-pregnant bitch expresses OTR. The distribution or relative expression of OTR does not differ between uterine horn and body in dioestrus or anoestrus except in LE. LE may have more oxytocin-dependent activity during dioestrus than anoestrus.

Cyclic AMP Effectors Regulate Myometrial Oxytocin Receptor Expression.

The factors that initiate human labor are poorly understood. We have tested the hypothesis that a decline in cAMP/protein kinase A (PKA) function leads to the onset of labor. Initially, we identified myometrial cAMP/PKA-responsive genes (six up-regulated and five down-regulated genes) and assessed their expression in myometrial samples taken from different stages of pregnancy and labor. We found that the oxytocin receptor (OTR) was one of the cAMP-repressed genes, and, given the importance of OTR in the labor process, we studied the mechanisms involved in greater detail using small interfering RNA, chemical agonists, and antagonists of the cAMP effectors. We found that cAMP-repressed genes, including OTR, increased with the onset of labor. Our in vitro studies showed that cAMP acting via PKA reduced OTR expression but that in the absence of PKA, cAMP acts via exchange protein activated by cAMP (EPAC) to increase OTR expression. In early labor myometrial samples, PKA levels and activity declined and Epac1 levels increased, perhaps accounting for the increase in myometrial OTR mRNA and protein levels at this time. In vitro exposure of myometrial cells to stretch and IL-1β increased OTR levels and reduced basal and forskolin-stimulated cAMP and PKA activity, as judged by phospho-cAMP response element-binding protein levels, but neither stretch nor IL-1β had any effect on PKA or EPAC1 levels. In summary, there is a reduction in the activity of the cAMP/PKA pathway with the onset of human labor potentially playing a critical role in regulating OTR expression and the transition from myometrial quiescence to activation.

Reduced oxytocin receptor gene expression and binding sites in different brain regions in schizophrenia: A post-mortem study

Schizophrenia is a severe neuropsychiatric disorder with impairments in social cognition. Several brain regions have been implicated in social cognition, including the nucleus caudatus, prefrontal and temporal cortex, and cerebellum. Oxytocin is a critical modulator of social cognition and the formation and maintenance of social relationships and was shown to improve symptoms and social cognition in schizophrenia patients. However, it is unknown whether the oxytocin receptor is altered in the brain.Therefore, we used qRT-PCR and Ornithine Vasotocin Analog ([125I]OVTA)-based receptor autoradiography to investigate oxytocin receptor expression at both the mRNA and protein level in the left prefrontal and middle temporal cortex, left nucleus caudatus, and right posterior superior vermis in 10 schizophrenia patients and 6 healthy controls. Furthermore, to investigate confounding effects of long-term antipsychotic medication we treated rats with clozapine or haloperidol for 12weeks and assessed expression of the oxytocin receptor in cortical and subcortical brain regions.In schizophrenia patients, we found a downregulation of oxytocin receptor mRNA in the temporal cortex and a decrease in receptor binding in the vermis. In the other regions, the results showed trends in the same direction, without reaching statistical significance. We found no differences between antipsychotic-treated rats and controls.Downregulated expression and binding of the oxytocin receptor in brain regions involved in social cognition may lead to a dysfunction of oxytocin signaling. Our results support a dysfunction of the oxytocin receptor in schizophrenia, which may contribute to deficits of social cognition.

Sex Differences in the Embryonic Development of the Central Oxytocin System in Mice.

Recent studies suggest that oxytocin (OXT) may be important for organising the neural circuitry that underlies adult social behaviour. Although most of the work exploring these effects has focused on early postnatal development, there is evidence that OXT may also be important during foetal development. However, without an understanding of how the OXT system develops, the ability to functionally link OXT in foetal life to adult behaviour is limited. To understand where and when OXT could be acting during embryonic development to affect the organisation of neural substrates, we examined the development of the mouse OXT system from embryonic day (E) 12.5 through postnatal day (PND) 2 using OXT receptor (OXTR) binding and a quantitative polymerase chain reaction. In both males and females, OXTR binding was observed by E16.5 in the ventricular and subventricular zones, as well as the developing amygdala. In males, OXT mRNA was not detectable until PND2, whereas it was detectable by E16.5 in females. OXTR mRNA was detected by E12.5 in both sexes, although females appear to have more OXTR mRNA during foetal development than males. The present study is significant because it is the first to reveal an unexpected sex difference in the development of the OXT system and supports the possibility that OXT during foetal development may contribute to sex differences in adult behaviour.

Oxytocin Acting in the Nucleus Accumbens Core Decreases Food Intake.

Central oxytocin (OT) promotes feeding termination in response to homeostatic challenges, such as excessive stomach distension, salt loading and toxicity. OT has also been proposed to affect feeding reward by decreasing the consumption of palatable carbohydrates and sweet tastants. Because the OT receptor (OTR) is expressed in the nucleus accumbens core (AcbC) and shell (AcbSh), a site regulating diverse aspects of eating behaviour, we investigated whether OT acts there to affect appetite in rats. First, we examined whether direct AcbC and AcbSh OT injections affect hunger- and palatability-driven consumption. We found that only AcbC OT infusions decrease deprivation-induced chow intake and reduce the consumption of palatable sucrose and saccharin solutions in nondeprived animals. These effects were abolished by pretreatment with an OTR antagonist, L-368,899, injected in the same site. AcbC OT at an anorexigenic dose did not induce a conditioned taste aversion, which indicates that AcbC OT-driven anorexia is not caused by sickness/malaise. The appetite-specific effect of AcbC OT is supported by the real-time polymerase chain reaction analysis of OTR mRNA in the AcbC, which revealed that food deprivation elevates OTR mRNA expression, whereas saccharin solution intake decreases OTR transcript levels. We also used c-Fos immunohistochemistry as a marker of neuronal activation and found that AcbC OT injection increases activation of the AcbC itself, as well as of two feeding-related sites: the hypothalamic paraventricular and supraoptic nuclei. Finally, considering the fact that OT plays a significant role in social behaviour, we examined whether offering animals a meal in a social setting would modify their hypophagic response to AcbC OT injections. We found that a social context abolishes the anorexigenic effects of AcbC OT. We conclude that OT acting via the AcbC decreases food intake driven by hunger and reward in rats offered a meal in a nonsocial setting.

Distinct Effects of Estrogen on Mouse Maternal Behavior: The Contribution of Estrogen Synthesis in the Brain.

Estrogen surge following progesterone withdrawal at parturition plays an important role in initiating maternal behavior in various rodent species. Systemic estrogen treatment shortens the latency to onset of maternal behavior in nulliparous female rats that have not experienced parturition. In contrast, nulliparous laboratory mice show rapid onset of maternal behavior without estrogen treatment, and the role of estrogen still remains unclear. Here the effect of systemic estrogen treatment (for 2 h, 1 day, 3 days, and 7 days) after progesterone withdrawal was examined on maternal behavior of C57BL/6 mice. This estrogen regimen led to different effects on nursing, pup retrieval, and nest building behaviors. Latency to nursing was shortened by estrogen treatment within 2 h. Moreover, pup retrieval and nest building were decreased. mRNA expression was also investigated for estrogen receptor α (ERα) and for genes involved in regulating maternal behavior, specifically, the oxytocin receptor (OTR) and vasopressin receptor in the medial amygdala (MeA) and medial preoptic area (MPOA). Estrogen treatment led to decreased ERα mRNA in both regions. Although OTR mRNA was increased in the MeA, OTR and vasopressin receptor mRNA were reduced in the MPOA, showing region-dependent transcription regulation. To determine the mechanisms for the actions of estrogen treatment, the contribution of estrogen synthesis in the brain was examined. Blockade of estrogen synthesis in the brain by systemic letrozole treatment in ovariectomized mice interfered with pup retrieval and nest building but not nursing behavior, indicating different contributions of estrogen synthesis to maternal behavior. Furthermore, letrozole treatment led to an increase in ERα mRNA in the MeA but not in the MPOA, suggesting that involvement of estrogen synthesis is brain region dependent. Altogether, these results suggest that region-dependent estrogen synthesis leads to differential transcriptional activation due to exogenous estrogen treatment, and thereby results in different effects on maternal behavior.

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

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