Oxytocin Receptor Density Research Articles

Oxytocin in the ventromedial hypothalamic nucleus reduces feeding and acutely increases energy expenditure.

Central oxytocin reduces food intake and increases energy expenditure. The ventromedial hypothalamic nucleus (VMN) is associated with energy balance and contains a high density of oxytocin receptors. We hypothesized that oxytocin in the VMN is a negative regulator of energy balance acting to reduce feeding and increase energy expenditure. To test this idea, oxytocin or vehicle was injected directly into the VMN of Sprague-Dawley rats during fasted and nonfasted conditions. Energy expenditure (via indirect calorimetry) and spontaneous physical activity (SPA) were recorded simultaneously. Animals were also exposed to a conditioned taste aversion test, to determine whether oxytocin's effects on food intake were associated with malaise. When food was available during testing, oxytocin-induced elevations in energy expenditure lasted for 1 h, after which overall energy expenditure was reduced. In the absence of food during the testing period, oxytocin similarly increased energy expenditure during the first hour, but differences in 12-h energy expenditure were eliminated, implying that the differences may have been due to the thermic effects of feeding (digestion, absorption, and metabolic processing). Oxytocin acutely elevated SPA and reduced feeding at doses that did not cause a conditioned taste aversion during both the fed and fasted states. Together, these data suggest that oxytocin in the VMN promotes satiety and acutely elevates energy expenditure and SPA and implicates the VMN as a relevant site for the antiobesity effects of oxytocin.

Comparative analysis of oxytocin receptor density in the nucleus accumbens: An adaptation for female and male alloparental care?

Parental behavior is commonly displayed by progenitors. However, other individuals, genetically related (e.g. siblings, aunts, uncles) or not with the newborns, also display parental behavior (commonly called alloparental, or adoptive behavior). I hypothesize that species that live in family or social groups where other non-reproductive members (males and females) take care of infants, have brain adaptations to promote or facilitate that behavioral response. The present work revises the evidence supporting the hypothesis that high density of oxytocin receptors (OXTR) in the nucleus accumbens (NA) is one of those adaptations. All species known to have high NA OXTR show not only female, but also male alloparental care. Therefore, I predict that high NA OXTR could be present in all species in which juvenile and adult male alloparental behavior have been observed. Strategies to test this and other alternative working hypothesis and its predictions are presented.

Natural variation in maternal care shapes adult social behavior in rats

Features of the early postnatal environment profoundly shape later physical and behavioral phenotypes. The amount of licking/grooming that rat dams direct towards their offspring has durable consequences, including behavioral and physiological dimensions of stress reactivity, cognition, and reproductive behavior. We examined how natural variation in maternal care alters social behavior in adult offspring and how this relates to anxiety behavior and oxytocin receptor density. Male and female offspring of mothers who received high levels of licking spent significantly more time in social contact with unfamiliar individuals than did offspring whose dams provided less grooming. Reduced anxiety behavior was associated with greater social interaction. No differences in oxytocin receptor binding assessed by (125) I-OVTA autoradiography were detected between groups. The present investigation characterizes a novel impact of maternal care on adult social interaction behavior, replicates anxiety behavior differences, and illustrates connections between social behavior and anxiety in adulthood across maternal treatment groups.

Chronic methamphetamine treatment induces oxytocin receptor up-regulation in the amygdala and hypothalamus via an adenosine A2A receptor-independent mechanism

There is mounting evidence that the neuropeptide oxytocin is a possible candidate for the treatment of drug addiction. Oxytocin was shown to reduce methamphetamine self-administration, conditioned place-preference, hyperactivity and reinstatement in rodents, highlighting its potential for the management of methamphetamine addiction. Thus, we hypothesised that the central endogenous oxytocinergic system is dysregulated following chronic methamphetamine administration. We tested this hypothesis by examining the effect of chronic methamphetamine administration on oxytocin receptor density in mice brains with the use of quantitative receptor autoradiographic binding. Saline (4ml/kg/day, i.p.) or methamphetamine (1mg/kg/day, i.p.) was administered daily for 10days to male, CD1 mice. Quantitative autoradiographic mapping of oxytocin receptors was carried out with the use of [125I]-vasotocin in brain sections of these animals. Chronic methamphetamine administration induced a region specific upregulation of oxytocin receptor density in the amygdala and hypothalamus, but not in the nucleus accumbens and caudate putamen. As there is evidence suggesting an involvement of central adenosine A2A receptors on central endogenous oxytocinergic function, we investigated whether these methamphetamine-induced oxytocinergic neuroadaptations are mediated via an A2A receptor-dependent mechanism. To test this hypothesis, autoradiographic oxytocin receptor binding was carried out in brain sections of male CD1 mice lacking A2A receptors which were chronically treated with methamphetamine (1mg/kg/day, i.p. for 10days) or saline. Similar to wild-type animals, chronic methamphetamine administration induced a region-specific upregulation of oxytocin receptor binding in the amygdala and hypothalamus of A2A receptor knockout mice and no genotype effect was observed. These results indicate that chronic methamphetamine use can induce profound neuroadaptations of the oxytocinergic receptor system in brain regions associated with stress, emotionality and social bonding and that these neuroadaptations are independent on the presence of A2A receptors. These results may at least partly explain some of the behavioural consequences of chronic methamphetamine use.

Variations in oxytocin receptor (OTR) density in term trophoblast depend on the contactile activity of the uterus

Oxytocin (OT) stimulates uterine contractions during labor. Before initiation of labor, increased sensitivity to OT must be accompanied by a strong upregulation of OTR in the myometrium and decidua. Despite OTR is present in the placental trophoblast cells, its expression and role in the context of uterine contractions or placental separation have not been studied thoroughly. Here we examined comparatively term placentae (Group I; N = 12) obtained after cesarean sections performed without spontaneously induced uterine contractions and placentae delivered after normal labors (Group II; N = 12). Mean OT concentrations was measured by ELISA in the placental samples taken from maternal surface. Next, the cytotrophoblast cells were isolated using Kliman's method based on trypsin, DNase and a 5–70% Percoll gradient centrifugation, and cultured in normoxia. After 5 days the cultures were fixed and immunostained for OTR. Quantitative morphometry was applied for evaluation of OTR expression. There were no significant differences in the mean OT concentration between the groups (p >; 0.05), whereas 11.2‐fold increase in the expression of OTR was observed in trophoblast cultures established in Group I. Thus, induction of labor with normal uterine contractions involves upregulation of OTR in placental region contiguous to the uterine wall. It may be crucial for the course of third stage of labor.

Oxytocin, Feeding, and Satiety

Oxytocin neurons have a physiological role in food intake and energy balance. Central administration of oxytocin is powerfully anorexigenic, reducing food intake and meal duration. The central mechanisms underlying this effect of oxytocin have become better understood in the past few years. Parvocellular neurons of the paraventricular nucleus project to the caudal brainstem to regulate feeding via autonomic functions including the gastrointestinal vago-vagal reflex. In contrast, magnocellular neurons of the supraoptic and paraventricular nuclei release oxytocin from their dendrites to diffuse to distant hypothalamic targets involved in satiety. The ventromedial hypothalamus, for example, expresses a high density of oxytocin receptors but does not contain detectable oxytocin nerve fibers. Magnocellular neurons represent targets for the anorexigenic neuropeptide α-melanocyte stimulating hormone. In addition to homeostatic control, oxytocin may also have a role in reward-related feeding. Evidence suggests that oxytocin can selectively suppress sugar intake and that it may have a role in limiting the intake of palatable food by inhibiting the reward pathway.

Long chain polyunsaturated fatty acids alter oxytocin signaling and receptor density in cultured pregnant human myometrial smooth muscle cells.

Epidemiological studies and interventional clinical trials indicate that consumption of long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) such as docosahexaenoic acid (DHA) lengthen gestational duration. Although the mechanisms are not well understood, prostaglandins (PG) of the 2-series are known to play a role in the initiation and progress of labor. In animal studies, modest DHA provision has been shown to reduce placental and uterine PGE2 and PGF2α, matrix metalloproteinase (MMP)-2 and MMP-9 expression, and placental collagenase activity. However, modulation of PG biosynthesis may not account for all the effects of LC n-3 PUFAs in labor. We investigated one potential PG-independent mechanism of LC PUFA action using cultured pregnant human myometrial smooth muscle cells. Our goal was to characterize the effect of LC PUFA treatment on oxytocin signaling, a potent uterotonic hormone involved in labor. The addition of 10 µM–100 µM DHA or arachidonic acid (AA) to the culture media for 48 h resulted in dose dependent enrichment of these fatty acids in membrane lipid. DHA and AA significantly inhibited phosphatidylinositol turnover and [Ca2+]i mobilization with oxytocin stimulation compared to bovine serum albumin control and equimolar oleic acid. DHA and AA significantly reduced oxytocin receptor membrane concentration without altering binding affinity or rate of receptor internalization. These findings demonstrate a role for LC n-3 PUFAs in regulation of oxytocin signaling and provide new insight into additional mechanisms pertaining to reports of dietary fish and fish oil consumption prolonging gestation.

Variation in maternal and anxiety-like behavior associated with discrete patterns of oxytocin and vasopressin 1a receptor density in the lateral septum

The relationship between anxiety and maternal behavior has been explored across species using a variety of approaches, yet there is no clear consensus on the nature or direction of this relationship. In the current study, we have assessed stable individual differences in anxiety-like behavior in a large cohort (n=57) of female F2 hybrid mice. Using open-field behavior as a continuous and categorical (high vs. low) measure we examined the relationship between the anxiety-like behavior of virgin F2 females and the subsequent maternal behavior of these females. In addition, we quantified oxytocin (OTR) and vasopressin (V1a) receptor density within the lateral septum to determine the possible correlation with anxiety-like and maternal behavior. We find that, though activity levels within the open-field do predict latency to engage in pup retrieval, anxiety-like measures on this test are otherwise not associated with subsequent maternal behavior. OTR density in the dorsal lateral septum was found to be negatively correlated with activity levels in the open-field and positively correlated with frequency of nursing behavior. V1a receptor density was significantly correlated with postpartum licking/grooming of pups. Though we do not find support for the hypothesis that individual differences in trait anxiety predict variation in maternal behavior, we do find evidence for the role of OTR and V1a receptors in predicting maternal behavior in mice and suggest possible methodological issues (such as distinguishing between trait and state anxiety) that will be a critical consideration for subsequent studies of the anxiety–maternal behavior relationship.This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.

Oxytocin receptor density is associated with male mating tactics and social monogamy

Despite its well-described role in female affiliation, the influence of oxytocin on male pairbonding is largely unknown. However, recent human studies indicate that this nonapeptide has a potent influence on male behaviors commonly associated with monogamy. Here we investigated the distribution of oxytocin receptors (OTR) throughout the forebrain of the socially monogamous male prairie vole (Microtus ochrogaster). Because males vary in both sexual and spatial fidelity, we explored the extent to which OTR predicted monogamous or non-monogamous patterns of space use, mating success and sexual fidelity in free-living males. We found that monogamous males expressed higher OTR density in the nucleus accumbens than non-monogamous males, a result that mirrors species differences in voles with different mating systems. OTR density in the posterior portion of the insula predicted mating success. Finally, OTR in the hippocampus and septohippocampal nucleus, which are nuclei associated with spatial memory, predicted patterns of space use and reproductive success within mating tactics. Our data highlight the importance of oxytocin receptor in neural structures associated with pairbonding and socio-spatial memory in male mating tactics. The role of memory in mating systems is often neglected, despite the fact that mating tactics impose an inherently spatial challenge for animals. Identifying mechanisms responsible for relating information about the social world with mechanisms mediating pairbonding and mating tactics is crucial to fully appreciate the suite of factors driving mating systems.This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.

Variations in Maternal Behavior—Oxytocin and Reward Pathways—Peripheral Measures Matter?!

Variations in Maternal Behavior—Oxytocin and Reward Pathways—Peripheral Measures Matter?!

Increasing oxytocin receptor expression in the nucleus accumbens of pre-pubertal female prairie voles enhances alloparental responsiveness and partner preference formation as adults

Oxytocin receptors (OXTR) in the nucleus accumbens (NAcc) promote alloparental behavior and partner preference formation in female prairie voles. Within the NAcc there is significant individual variation in OXTR binding and virgin juvenile and adult females with a high density of OXTR in the NAcc display an elevated propensity to engage in alloparental behavior toward novel pups. Over-expression of OXTR in the NAcc of adult female prairie voles using viral vector gene transfer facilitates partner preference formation, but has no effect on alloparental behavior, even though OXTR antagonists infused into the NAcc blocks both behaviors. We therefore hypothesized that long-term increases in OXTR signaling during development may underlie the relationship between adult OXTR density in the NAcc and alloparental behavior. To test this hypothesis, we used viral vector gene transfer to increase OXTR density in the NAcc of prepubertal, 21day old female prairie voles and tested for both alloparental behavior and partner preference formation as adults. Consistent with a developmental impact of OXTR signaling, adults over-expressing OXTR from weaning display both increased alloparental behavior and partner preference formation. Thus, the relatively acute impact of elevated OXTR signaling in the NAcc on partner preference formation previously reported appears to be dissociable from the effects of longer term, developmentally relevant OXTR signaling necessary for modulating alloparental behavior. These results are consistent with the hypothesis that oxytocin can have both long-term “organizational” effects as well as acute “activational” effects on affiliative behaviors.

Oxytocin and same-sex social behavior in female meadow voles

The neuropeptide oxytocin (OT) has been implicated in a range of mammalian reproductive and social behaviors including parent-offspring bonding and partner preference formation between socially monogamous mates. Its role in mediating non-reproductive social relationships in rodents, however, remains largely unexplored. We examined whether OT facilitates same-sex social preferences between female meadow voles—a species that forms social nesting groups in short, winter-like day lengths. In contrast to results from studies of opposite-sex attachment between prairie vole mates, we found that neither OT nor dopamine neurotransmission was required for baseline levels of social partner preference formation or expression. OT enhanced preference formation beyond baseline levels—an effect that was counteracted by treatment with an oxytocin receptor antagonist (OTA). Oxytocin receptor (OTR) density correlated with social behavior in brain regions not known to be associated with opposite-sex affiliation, including the lateral septum and central amygdala. In addition, voles housed in short day lengths (SD) exhibited higher levels of OTR binding in the central amygdala, and voles exposed to high concentrations of estradiol exhibited less binding in the nucleus accumbens (NAcc) and increased binding in the ventromedial nucleus of the hypothalamus. These results suggest that same-sex social behavior shares common elements with other mammalian social behaviors affected by OT, but that the specific neural pathways through which OT exerts its influence are likely distinct from those known for sexual attachments.

Brainstem oxytocinergic modulation of heart rate control in rats: effects of hypertension and exercise training

Oxytocinergic brainstem projections participate in the autonomic control of the circulation. We investigated the effects of hypertension and training on cardiovascular parameters after oxytocin (OT) receptor blockade within the nucleus tractus solitarii (NTS) and NTS OT and OT receptor expression. Male spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were trained (55% of maximal exercise capacity) or kept sedentary for 3 months and chronically instrumented (NTS and arterial cannulae). Mean arterial blood pressure (MAP) and heart rate (HR) were measured at rest and during an acute bout of exercise after NTS pretreatment with vehicle or OT antagonist (20 pmol of OT antagonist (200 nl of vehicle)(-1)). Oxytocin and OT receptor were quantified ((35)S-oligonucleotide probes, in situ hybridization) in other groups of rats. The SHR exhibited high MAP and HR (P < 0.05). Exercise training improved treadmill performance and reduced basal HR (on average 11%) in both groups, but did not change basal MAP. Blockade of NTS OT receptor increased exercise tachycardia only in trained groups, with a larger effect on trained WKY rats (+31 +/- 9 versus +12 +/- 3 beats min(1) in the trained SHR). Hypertension specifically reduced NTS OT receptor mRNA density (-46% versus sedentary WKY rats, P < 0.05); training did not change OT receptor density, but significantly increased OT mRNA expression (+2.5-fold in trained WKY rats and +15% in trained SHR). Concurrent hypertension- and training-induced plastic (peptide/receptor changes) and functional adjustments (HR changes) of oxytocinergic control support both the elevated basal HR in the SHR group and the slowing of the heart rate (rest and exercise) observed in trained WKY rats and SHR.

The Meaning of Weaning: Influence of the Weaning Period on Behavioral Development in Mice

Maternal care during the first week postpartum has long-term consequences for offspring development in rodents. However, mother-infant interactions continue well beyond this period, with several physiological and behavioral changes occurring between days 18 and 28 PN. In the present study, we investigate the long-term effects on offspring behavior of being weaned at day 21 PN versus day 28 PN. We found that male and female offspring engage in higher initial levels of social interaction if weaned at day 28 PN, as well as sexually dimorphic changes in exploratory behavior. Females who were themselves weaned earlier also appeared to wean their own pups earlier. Sex-specific effects of weaning age were found on levels of oxytocin and vasopressin V1a receptor density in the hypothalamus, central nucleus of the amygdala and nucleus accumbens. These results indicate that altering weaning age in mice may be a useful model for investigating the development of sexual dimorphism in neurobiology and behavior.

The story of O – is oxytocin the mediator of the placebo response?

While the placebo responses in various medical conditions have been shown to follow a few basic principles such as expectancies, reward learning and Pavlovian conditioning, the underlying neurobiology and the mediating hormonal and/or neuromodulating processing have remained obscure. We here report the collected evidence that oxytocin (OXT), a 389-amino acid polypeptide located on chromosome 3p25 that is released in the brain (hypothalamus) and in peripheral tissue, is the central mediator of the placebo response: we hypothesize that exogenous OXT via an OXT agonist will enhance the placebo response, while exogenous OXT blockade by an antagonist will reduce the placebo response in placebo analgesia and other placebo models. It is furthermore proposed that the placebo response in trials may be predicted by circulating plasma OXT levels, the OXT receptor density in the brain and/or the presence of one or more of the single nucleotide polymorphisms of the OXT promoter gene.

Involvement of oxytocin and its receptor in nociceptive modulation in the central nucleus of amygdala of rats

Studies have demonstrated that oxytocin plays important roles in pain modulation in the central nervous system. Oxytocin-ergic neurons are found in paraventricular nucleus and supraoptic nucleus of the hypothalamus. The oxytocin-ergic neurons send fibers from hypothalamus to amygdala and high density of oxytocin receptors are found in the central nucleus of amygdala (CeA). The present study was performed to investigate the influences of oxytocin and its receptors on nociceptive responses in the CeA of rats. Intra-CeA injection of 0.1, 0.5 or 1 nmol of oxytocin induced dose-dependent increases in the handpaw withdrawal latency induced by noxious thermal and mechanical stimulation in rats. The oxytocin-induced anti-nociception could be blocked by the selective oxytocin antagonist 1-deamino-2- d-Tyr-(Oet)-4-Thr-8-Orn-oxytocin. The present study demonstrated that oxytocin and its receptors are involved in nociceptive modulation in the CeA of rats.

Oxytocin administration, but not social housing condition, reduces growth rate of human breast cancer xenografts (MCF7) in SCID mice.

Abstract Abstract #5076 Background: Oxytocin decreases human breast cancer cell proliferation in vitro and oxytocin receptors are reported to be present on at least 80% of human breast tumors. Animal studies show increased oxytocin levels in association with pair bonding, maternal care giving and mating behavior. Our experiment tested two hypotheses: 1) exogenous administration of oxytocin(OT) and 2) sibling-group housing, compared to individual housing, will reduce the growth in human breast cancer cell -MCF7-xenografts in SCID mice. We also hypothesized this effect would be mediated by differences in circulating OT. Materials and Methods: A 2 X 2 design was used to study 48 animals. Half of the animals lived in group(GRP) housing, the others were housed singly(SGL). Half of the animals in each housing group received OT (10-9 M) administered by a continuous release pellet(Innovative Research of America) and the others received a placebo(PBO) pellet. At weaning(4 wks), SCID mice were randomized to individual cages vs. groups of 4 mice per cage. At maturation (vaginal cornification-8 wks), continuous release estrogen pellets were implanted and two days later MCF7 cells(0.1ml/10X106)were implanted in the mammary fat pad. Pellets containing OT or PBO were implanted, subcutaneously, 2 days after the MCF7 cells. Plasma was collected 2 days prior to and 2 days following pellet &amp; cell implantation, 14 days later and at sacrifice (41 – 60 d) for analysis of OT concentration using enzyme immunoassay (Assay Designs, Inc). Tumor volumes were measured every three days. Statistical Analyses: A natural log transformation of the plasma OT levels was used to reduce skewness in the observed values. Tumor volumes were converted to cubed root to linearize and a regression line was fit to generate tumor growth rate(slope). Differences in tumor growth rate by housing condition (GRP/SGL), oxy Rx(Y/N) and OT plasma levels were tested by mixed effects ANOVA. Results: OT plasma levels in animals with OT pellets, as compared to PBO, were significantly different at 2 &amp; 14 days after pellet implantation(p=0.001), but not at baseline or at sacrifice. OT plasma levels were higher in group vs single housing (p=.023). Due to the lack of difference in plasma OT at the time of sacrifice, we limited prediction of tumor growth rate to the first 29 days when OT pellets were secreting OT (extrapolation from levels at 2 &amp; 14 days). Slower tumor growth rate occurred with OT treatment compared to PBO(p=0.031), and with higher OT plasma levels(p=0.032) but not with group vs. single housing.&amp;#x2028; Discussion: Continuous oxytocin administration over 29 days produced increased oxytocin plasma levels and both were associated with reduced MCF7 xenograft growth rate in SCID mice. Our next step will be to test whether breast tumor oxytocin receptor density moderates the association between plasma oxytocin and tumor growth rate. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5076.

Social enrichment during postnatal development induces transgenerational effects on emotional and reproductive behavior in mice

Across species there is evidence that the quality of the early social environment can have a profound impact on neurobiology and behavior. In the present study we explore the effect of communal rearing conditions (three dams with three litters per cage) during the postnatal period on offspring (F1) and grand-offspring (F2) anxiety-like and maternal behavior in Balb/c mice. Females rearing pups in communal nests exhibited increased levels of postpartum maternal care and communal rearing was found to abolish sex-differences in weaning weights. In adulthood, communally reared offspring were observed to display reduced anxiety-like behavior when placed in a novel environment. When rearing their own offspring under standard conditions, communally reared females demonstrated higher levels of motivation to retrieve pups, built higher quality nests, and exhibited higher levels of postpartum care compared to standard reared females. When exposed to an intruder male, communally reared females were more subordinate and less aggressive. F2 offspring of communally reared females were observed to engage in reduced anxiety-like behavior, have larger litter sizes and an increased frequency of nursing on PND 1. Analysis of neuropeptide receptor levels suggest that a communal rearing environment may exert sustained effects on behavior through modification of oxytocin and vasopressin (V1a) receptor densities. Though Balb-C mice are often considered “socially-incompetent” and high in anxiety-like behavior, our findings suggest that through enrichment of the postnatal environment, these behavioral and neuroendocrine deficits may be attenuated both within and across generations.

Species and individual differences in juvenile female alloparental care are associated with oxytocin receptor density in the striatum and the lateral septum

The neuropeptide oxytocin has been implicated in the regulation of affiliative behavior and maternal responsiveness in several mammalian species. Rodent species vary considerably in the expression of juvenile alloparental behavior. For example, alloparental behavior is spontaneous in juvenile female prairie voles (∼20 days of age), takes 1–3 days of pup exposure to develop in juvenile rats, and is nearly absent in juvenile mice and meadow voles. Here, we tested the hypothesis that species differences in pup responsiveness in juvenile rodents are associated with oxytocin receptor (OTR) density in specific brain regions. We found that OTR density in the nucleus accumbens (NA) is highest in juvenile prairie voles, intermediate in juvenile rats, and lowest in juvenile mice and meadow voles. In the caudate putamen (CP), OTR binding was highest in prairie voles, intermediate in rats and meadow voles, and lowest in mice. In contrast, the lateral septum (LS) shows an opposite pattern, with OTR binding being high in mice and meadow voles and low in prairie voles and rats. Thus, alloparental responsiveness in juvenile rodents is positively correlated with OTR density in the NA and CP and negatively correlated with OTR density in the LS. We then investigated whether a similar receptor–behavior relationship exists among juvenile female prairie voles by correlating individual variation in alloparental behavior with variation in OTR density. The time spent adopting crouching postures, the most distinctive component of alloparental behavior in juveniles, was positively correlated with OTR density in the NA ( r = 0.47) and CP ( r = 0.45) and negatively correlated with OTR density in the lateral septum ( r = −0.53). Thus, variation in OTR density in the NA, CP, and LS may underlie both species and individual differences in alloparental care in rodents.

Oxytocin receptors in the nucleus accumbens facilitate “spontaneous” maternal behavior in adult female prairie voles

Oxytocin and the nucleus accumbens have been extensively implicated in the regulation of maternal behavior, and the processing of pup-related stimuli relevant for this behavior. Oxytocin receptor density in the nucleus accumbens is highly variable in virgin female prairie voles, as is their behavioral response to pups, ranging from neglecting and infanticidal to full maternal behavior. We hypothesized that oxytocin receptor in the nucleus accumbens facilitates the expression of “spontaneous” maternal behavior in prairie voles. Forty sexually-naive adult females were exposed to pups for the first time and tested for maternal behavior. Oxytocin receptor binding in the nucleus accumbens and other brain regions was later determined using autoradiography. Females that showed maternal behavior (lick and groom the pups and hover over them for at least 30 s, n=24) had higher oxytocin receptor density in the nucleus accumbens (shell subregion) ( P<0.05) than females that did not show maternal behavior or attacked the pups ( n=16). No differences were found in other brain regions (medial preoptic area, septum, prelimbic cortex). In a second experiment, we tested whether infusions of the oxytocin receptor antagonist (d(CH 2) 5 1,Tyr(Me) 2,Orn 8)-AVT into the nucleus accumbens would block “spontaneous” maternal behavior. As a control region, oxytocin receptor antagonist was also infused into the caudate putamen. Ten females were infused bilaterally into the nucleus accumbens or caudate putamen with either 2 ng/0.5 μl of oxytocin receptor antagonist or CSF (vehicle). While five of 10 nucleus accumbens CSF-infused animals showed maternal behavior, none of the nucleus accumbens oxytocin receptor antagonist-infused subjects did (0/10; χ 2, P<0.01). Nucleus accumbens oxytocin receptor antagonist-infused females recovered the next day and were not different from controls. Animals infused with CSF or oxytocin receptor antagonist into the caudate putamen did not differ (four/10, four/10). This is the first study to show that the nucleus accumbens is involved in the regulation of “spontaneous” maternal behavior and that oxytocin receptor in this brain region facilitates maternal responses.