Oxytocin antagonist treatments alter the formation of pair relationships in zebra finches of both sexes

Oxytocin and vasopressin are known to be important in affiliative behaviors. Although these peptides have been shown to be involved in monogamous pairing behavior in a few mammalian species, their role across monogamous species is not well understood. In particular, monogamy is most common in birds, yet the role of mesotocin and vasotocin (avian homologues of oxytocin and vasopressin) in pair relationships has not been established in any avian species. The goal of the present study was to investigate the effects of an oxytocin antagonist on pairing and pairing-related behaviors in the monogamous zebra finch. To accomplish this, we systemically administered one of three doses of an oxytocin antagonist (1 μg, 5 μg, or 10 μg) or a vehicle to adult male and female zebra finches (in separate experiments) with no prior pairing experience. Subjects were observed over three days and allowed to choose mates. We found that oxytocin antagonists increased the latency to pair and decreased pair formation in both sexes. The effects of these treatments on overall pairing behaviors were more pronounced in females than in males, suggesting sexually differentiated effects on motivation to contact conspecifics. Treatments also reduced courtship, as measured by directed singing, in males. These results suggest that nonapeptides play a key role in pair formation in zebra finches of both sexes, similar to findings in other monogamous species.     

Central oxytocin receptors mediate mating-induced partner preferences and enhance correlated activation across forebrain nuclei in male prairie voles

Oxytocin (OT) is a deeply conserved nonapeptide that acts both peripherally and centrally to modulate reproductive physiology and sociosexual behavior across divergent taxa, including humans. In vertebrates, the distribution of the oxytocin receptor (OTR) in the brain is variable within and across species, and OTR signaling is critical for a variety of species-typical social and reproductive behaviors, including affiliative and pair bonding behaviors in multiple socially monogamous lineages of fishes, birds, and mammals. Early work in prairie voles suggested that the endogenous OT system modulates mating-induced partner preference formation in females but not males; however, there is significant evidence that central OTRs may modulate pair bonding behavior in both sexes. In addition, it remains unclear how transient windows of central OTR signaling during sociosexual interaction modulate neural activity to produce enduring shifts in sociobehavioral phenotypes, including the formation of selective social bonds. Here we re-examine the role of the central OT system in partner preference formation in male prairie voles using a selective OTR antagonist delivered intracranially. We then use the same antagonist to examine how central OTRs modulate behavior and immediate early gene (Fos) expression, a metric of neuronal activation, in males during brief sociosexual interaction with a female. Our results suggest that, as in females, OTR signaling is critical for partner preference formation in males and enhances correlated activation across sensory and reward processing brain areas during sociosexual interaction. These results are consistent with the hypothesis that central OTR signaling facilitates social bond formation by coordinating activity across a pair bonding neural network.     

The effects of neonatal paternal deprivation on pair bonding, NAcc dopamine receptor mRNA expression and serum corticosterone in mandarin voles

High levels of paternal care are important for the development of social behavior in monogamous rodents. However, the effects of paternal care on the formation of pair bonding and underlying neuroendocrine mechanisms, especially the involvements of dopamine system and corticosterone, are not well understood. We investigated effects of paternal deprivation on pair bonding in mandarin voles (Microtus mandarinus), a socially monogamous rodent. Paternal deprivation was found to inhibit the formation of pair bonding in females according to partner preference tests (PPT). Paternal deprivation also reduced body contact behavior and increased aggression in males and females in PPT. During social interaction tests (SIT), paternal deprivation was found to reduce investigative and aggressive behaviors but increase body contact and self-grooming in females, and reduce staring, aggression, body contact and self-grooming in males when interacting with the opposite sex. Paternal deprivation reduced the expression of dopamine 1-type receptor (D1R) mRNA and dopamine 2-type receptor (D2R) mRNA in the nucleus accumbens of female offspring in later life, but enhanced mRNA expression of these two dopamine receptors in males. After three days of cohabitation the expression of D1R mRNA and D2R mRNA was negatively correlated for voles reared by two parents, but positively correlated in paternally deprived animals. Paternal deprivation reduced serum corticosterone levels in females but had the opposite effect in males. Three days of cohabitation did not alter corticosterone levels of PD females, but reduced it in PC females. Our results provide substantial evidence that paternal deprivation inhibits the formation of pair bonding in female mandarin voles and alters social behavior later in life. These behavioral variations were possibly associated with sex-specific alterations in the expression of two types of dopamine receptors and serum corticosterone levels induced by paternal deprivation.     

小型田鼠:研究单配制进化与调控的模型

哺乳动物的单配制通常被认为是社会性单配制,它不是单纯地由性行为来决定,而是由诸多因素,包括长期的pair bond、夫妻双方共同抚育后代、免近亲交配以及雌雄两性相似等来决定的。在这篇综述中,我们论述了如何以啮齿类田鼠属(Microtus)为模型,通过比较研究来帮助我们理解社会性单配制的进化以及其神经调控机制。对田鼠属的研究不仅证实了单配制起源于艰苦的生存条件的假说,而且还证实了雌性性选择可能有利于维持单配制。不仅如此,哺乳动物单配制的进化还需要雄性的prosocial行为的不断强化。例如,亲近行为可以促进pairbond的形成并强化雄性对后代的哺育行为,而这种强化则来源于神经多肽催产素(OT)和加压素(AVP)与类固醇类激素的相互作用。催产素和加压素调控pairbond和双亲哺育行为的表达,而单配制和多配制田鼠的催产素和加压素受体在脑内的分布有显的不同。比较研究揭示了小型田鼠单配制的调控机制,而种内差异和行为上的可塑性则有助于我们进一步理解这种机制。比如,在某些条件下,多配制的草原田鼠(Microtus pennsylvanicu)的雄性个体具有哺育后代的行为。尽管草原田鼠的加压素Vla受体在脑内的分布与其他多配制的田鼠相似,但是如果脑室注射加压素,仍可以诱发其哺育后代的行为。同样是单配制的橙腹田鼠(Microtus ochrogaster),生活在：Illnois的显示出高水平的prosocial行为,而生活在Kansas的则表现出较低水平的社会性行为。即使两个种群的催产素或加压素Vla受体在脑内的分布相同,它们的雌激素受体表达水平显不同,这在雄性个体表现尤其明显。与Kansas的雄性个体相比,在终纹床核(bed rucleus of the stria tenninalis)和杏仁核中区(medial amygdala)这两个调控亲近行为和攻击行为的脑区,Illinois的雄性个体的α雌激素受体的水平要低得多。这些研究表明对雌激素的低敏感程度有利于高水平地表达prosocial行为并降低特定类型的攻击行为。     

Mating patterns in the golden lion tamarin (Leontopithecus rosalia): continuous receptivity and concealed estrus

Sociosexual behavior was monitored on a daily basis for 3 months in 5 pairs of golden lion tamarins (Leontopithecus rosalia). Urine samples were collected daily from each female and urinary estrogen cycles were determined by radioimmunoassay. Mounts and copulations were observed during all phases of the estrogen cycle. Peaks or regular cycles in sexual behavior were not documented. There were no significant changes in affiliative behavior by females or males that were associated with changes in urinary estrogen values. A negative relationship between pair bond duration and frequency of sexual interactions was observed: newly established pairs exhibited 2-6 times more frequent sexual behavior than a long-established pair. The lack of a conspicuous sexual signal in female golden lion tamarins may be related to a pattern of continuous sexual receptivity. Both reproductive patterns, concealed estrus and continuous receptivity, are explicable in relation to either monogamous or polyandrous mating systems.     

Pairing Patterns in Japanese Beetles (Popillia japonica Newman): Effects of Sex Ratio and Time of Day

Size-related patterns between unpaired and paired individuals and between males and females of a given pair give clues about both a species' sexual behavior and the environmental factors affecting its sexual behavior. We studied the mating patterns of Japanese beetles (Popillia japonica) in east–central Illinois. The frequency of male–female pairs varied significantly among days and within a day, with pairs being significantly more common in the morning and the evening. The sex ratio on the food plants was significantly male biased, but although the sex ratio fluctuated among days and among time periods, the variation in the frequency of mating pairs was not explained by variation in the sex ratio. We found no assortative pairing with respect to size, but sizes of paired and unpaired individuals did differ. Paired females were larger than unpaired females at all time periods. In contrast, paired males were larger at 0700 and smaller at 1000, and little difference existed at other times of the day. The size of males and females, sex ratio, and pairing frequency also differed among days. Much of this variation in size and pairing frequency was related to a seasonal effect: later in the summer, beetles of both sexes were smaller and pairs were less common. Interestingly, pairs were also less frequent on days with higher average temperatures. This between-day variation in pairing, in combination with the within-day pairing differences, suggests that the temperature may alter the cost, and hence likelihood, of pairing in this species.     

Social stimuli cause changes of plasma oxytocin and behavior in guinea pigs

The neuropeptide oxytocin (OXT) is a key factor in the initiation and regulation of sociosexual behavior. The present study analyzes the effects of cohabitation and social challenge on plasma OXT concentration rates in guinea pig pairs in relation to male sociosexual behavior. The cohabitation phase lasted 3 days. On day 4, the pair was socially challenged by introducing an unfamiliar male. Displayed male sexual behavior varied significantly during cohabitation, with peaks on day 1. Sociopositive behavior, i.e., side-by-side contact, was increased on days 3 and 4. Cohabitation per se led to elevated plasma OXT concentrations only in males. In contrast, both sexes reacted with increased plasma OXT concentrations to the social challenge (day 4). At that time, male OXT was significantly correlated with sexual behavior and female OXT with sociosexual behavior received from the partner. Additionally, pairs were synchronized in their OXT release during days 3 and 4. We conclude that cohabitation causes sexually dimorphic plasma OXT concentration patterns in guinea pigs. Secondly, the conformity of OXT release in both sexes may represent an endocrine marker for long-term cohabitation, which is reflected behaviorally by increased spatial proximity.     

Cellular mechanisms of social attachment

Pharmacological studies in prairie voles have suggested that the neuropeptides oxytocin and vasopressin play important roles in behaviors associated with monogamy, including affiliation, paternal care, and pair bonding. Our laboratory has investigated the cellular and neuroendocrine mechanisms by which these peptides influence affiliative behavior and social attachment in prairie voles. Monogamous prairie voles have a higher density of oxytocin receptors in the nucleus accumbens than do nonmonogamous vole species; blockade of these receptors by site-specific injection of antagonist in the female prairie vole prevents partner preference formation. Prairie voles also have a higher density of vasopressin receptors in the ventral pallidal area, which is the major output of the nucleus accumbens, than montane voles. Both the nucleus accumbens and ventral pallidum are key relay nuclei in the brain circuits implicated in reward, such as the mesolimbic dopamine and opioid systems. Therefore, we hypothesize that oxytocin and vasopressin may be facilitating affiliation and social attachment in monogamous species by modulating these reward pathways.     

雌雄同居对子午沙鼠情绪及下丘脑催产素表达的影响

雌雄同居是配偶关系形成的重要阶段,涉及到一系列生理和情绪的变化,对长期稳定的配偶关系形成具有重要意义。然而由于单配制动物模型较少,雌雄同居过程中的神经调控,尤其是两性差异仍不清楚。本研究以室内繁殖的子午沙鼠(Meriones meridianus)为研究对象,采用高架十字迷宫、强迫游泳和免疫组化法,探究雌雄同居对雌雄子午沙鼠的情绪变化及其相关脑区催产素表达的影响。结果表明：雌雄同居10 d后,在高架十字迷宫中,雌性沙鼠进入开放臂的频次显著减少(P <0.05),焦虑指数显著升高(P <0.05);在强迫游泳实验中,同居组雌性沙鼠停止游泳的频次和时间显著增加(P <0.05);同居组雌性沙鼠在下丘脑室旁核和视上核中的催产素表达水平显著升高(P <0.05)。然而同居组雄性的行为和催产素水平均没有出现显著变化,这可能与雌雄配偶关系形成过程中的两性不同步有关。综上,雌雄同居仅使得雌性子午沙鼠表现出焦虑样行为,且下丘脑催产素系统可能参与了该过程。     

根田鼠的熟悉性及其自然动情下的配偶选择

报道了在室内雌鼠自然动情条件下根田鼠两性个体配偶选择的3种熟悉性效应的5组实验结果,包括雌性对熟悉和陌生雄鼠、配偶和陌生雄鼠、配偶和熟悉雄鼠的择偶行为实验 , 雄性对熟悉和陌生雌鼠、配偶和陌生雌鼠的择偶行为实验。在实验前, 将1对性成熟的雌雄鼠 (非亲缘关系) 每天关养8 h 共8 d 建立熟悉性; 配对雌雄鼠至少生育1胎则为配偶关系。在 Y 形迷宫内的30 min 实验中, 两个被选择鼠分别以项链拴在横跨选择箱顶端中央的一根铁丝上, 限制它们在各自箱内活动; 而允许异性选择鼠从中立箱自由进入两个选择箱。记录选择鼠对异性被选择鼠的访问、社会探究、攻击、交配和友好行为的频次和时间。经Wilcoxon 关联样本 T 检验发现, 除交配行为不显著外, 雌性根田鼠均选择熟悉性较高的雄鼠; 而雄鼠不具这种选择性。该结果提示雌雄根田鼠的不同择偶行为也许就是反映该种婚配制度特征的直接行为过程。因此, 在择偶行为中, 雌性根田鼠表现的单配性倾向和雄鼠的多配性倾向, 只能以其婚配制度为一雄多雌制的假设来解释。我们的实验还说明在多配制田鼠中, 一雄多雌制与混交制在雌鼠择偶行为上是不同的, 而与单配制的相似或相近, 故简单地比较多配制与单配制则不能反映田鼠亚科动物婚配制度的多样性。     

The effect of pair bonding in Cabrera vole’s scent marking

The Cabrera vole (Microtus cabrerae) is a rare rodent living in patchy grassy areas of the Iberian Peninsula where unpaired individuals of both sexes use scent marking primarily to increase their mate-finding likelihood. Cabrera voles establish long-term pair bonds with opposite-sex conspecifics constituting a breeding pair, which is expected to reduce the efforts in searching for a new mate. Under such circumstances, scent marking as a strategy to increase mate-finding likelihood became useless. Accordingly, we hypothesise that pair bonded Cabrera voles suppress mate-finding scent marking to reduce energetic costs and predation risk. To test this hypothesis, we compared scent-marking behaviour towards a clean substrate, in both paired and non-paired voles. No differences were found in the scent marks’ type and the amount of marks placed by voles in both conditions. We also analysed the scent-marking behaviour of both sex pair bonded voles when exposed simultaneously to a clean substrate, a substrate pre-marked by males and a substrate pre-marked by females. We found no significant differences in scent-marks (urine-marked area and number of faecal boli) across the three types of substrate types. In accordance with our prediction, these results suggest that pair bonded Cabrera voles did not use scent marking for mate finding, thus providing further support to the existence of a monogamous mating strategy. Furthermore, our results fail to support the use of scent marking for territorial defence purposes.     

田鼠属动物婚配制度的研究范式

从社会组织的生态格局、熟悉性、社会等级和交配近况等择偶行为的影响因子,性二型和雄性射精能力等个体特征,配对关系的神经内分泌机制几方面综述了田鼠动物婚配制度的研究进展,同时从生态学、比较心理学、生理学、神经生物学等方面探讨择偶行类节式的特点。生态学方法,用鼠动物具有完整的婚配制度多样性格局,是婚配制度比较研究的哺乳动物类群。运用比较心理学方法,通过择偶行为实验可直接比较单配制与较研究的理想哺乳动物类     

Natural variation in paternal behavior is associated with central estrogen receptor alpha and oxytocin levels

In monogamous mammals paternal care plays an important role in the neural and behavioral development of offspring. However, the neuroendocrine mechanisms underlying paternal behavior remain poorly understood. Here, we investigate the association between natural variation in paternal responsiveness and central levels of oxytocin (OT) and estrogen receptor alpha (ERα). We used the frequency of licking and grooming behavior to distinguish low paternal responsiveness and high paternal responsiveness in virgin mandarin voles (Microtus mandarinus). Males that engaged in high paternal behavior had elevated levels of OT immunoreactive neurons in the paraventricular nuclei of the hypothalamus and supraoptic nuclei of the hypothalamus compared with males that displayed low paternal behavior. Likewise, males of high paternal responsiveness had more ERα immunoreactive neurons in the medial preoptic area, bed nucleus of the stria terminalis, arcuate nucleus of the hypothalamus and medial amygdaloid nucleus compared to low responsive males. The level of ERα immunoreactive neurons in the ventromedial hypothalamic nucleus was lower in highly paternal males compared to less paternal males. These results suggest that natural variation in paternal responsiveness may be directly related to variation in central OT and ERα.     

Sex Discrimination via Anal Gland Secretion in a Territorial Monogamous Mammal

Monogamy in mammals is relatively unusual, only occurring in 3–5% and to an even lesser degree in rodents. Monogamy exists in two forms, facultative which evolved due to female dispersion and obligate when male care is needed for offspring survival. Most monogamous rodents use scent marking as a form of territorial defence to obtain exclusive access to vital resources. Intrasexual competition occurs in many species to maintain pair bonds and also to signal presence within a territory. In this study, we tested the hypothesis that resident obligate monogamous Eurasian beaver (Castor fiber) can discriminate between the sexes when investigating anal gland secretions (AGS) from unknown (stranger) mated pairs. We predicted that, due to intrasexual competition, dominant territorial male and female beavers will display a stronger response to AGS of same‐sex conspecifics. Territorial intrusion by mated pair strangers was simulated by the formation of experimental scent mounds (ESM) with AGS. Our results showed that both sexes (1) displayed a stronger response to the male AGS in sniffing duration, (2) physically responded for longer durations towards male AGS and (3) overmarked male AGS more frequently. We infer that obligate monogamous mammals can determine the sexual identity of intruding conspecifics of a mated pair via AGS and that intruding males may pose more of a threat to resident males via intrasexual competition and resident females due to the long‐term costs, such as infanticide and abortion, of a new dominant male.     

Estrous phase alters social behavior in a polygynous but not a monogamous Peromyscus species

The social organization of rodent species determines behavioral patterns for both affiliative and agonistic encounters. The neuropeptide oxytocin has been implicated in the mediation of social behavior; however, variability in both neuropeptide expression and social behavior within a single species indicates an additional mediating factor. The purpose of the present comparative study was to investigate social behaviors in naïve mixed-sex pairs of monogamous Peromyscus californicus and polygynous Peromyscus leucopus. We identified substantial inter- and intra-specific variability in the expression of affiliative and agonistic behaviors. Although all P. californicus tested engaged in frequent and prolonged intervals of social contact and rarely engaged in aggressive behaviors, P. leucopus exhibited significant variability in both measures of social behaviors. The naturally occurring differences in social behavior displayed by P. leucopus vary across the estrous cycle, and correspond to hypothalamic oxytocin, as well as circulating oxytocin and glucocorticoid concentrations. These results provide evidence for a rhythm in social behavior across the estrous cycle in polygynous, but not monogamous, Peromyscus species.     

Neonatal paternal deprivation impairs social recognition and alters levels of oxytocin and estrogen receptor α mRNA expression in the MeA and NAcc,and serum oxytocin in mandarin voles

Paternal care is necessary for the healthy development of social behavior in monogamous rodents and social recognition underpins social behavior in these animals. The effects of paternal care on the development of social recognition and underlying neuroendocrine mechanisms, especially the involvement of oxytocin and estrogen pathways, remain poorly understood. We investigated the effects of paternal deprivation (PD: father was removed from neonatal pups and mother alone raised the offspring) on social recognition in mandarin voles (Microtus mandarinus), a socially monogamous rodent. Paternal deprivation was found to inhibit the development of social recognition in female and male offspring according to a habituation–dishabituation paradigm. Paternal deprivation resulted in increased inactivity and reduced investigation during new encounters with other animals. Paternal deprivation reduced oxytocin receptor (OTR) and estrogen receptor α (ERα) mRNA expression in the medial amygdala and nucleus accumbens. Paternal deprivation reduced serum oxytocin (OT) concentration in females, but had no effect on males. Our results provide substantial evidence that paternal deprivation inhibits the development of social recognition in female and male mandarin voles and alters social behavior later in life. This is possibly the result of altered expression of central OTR and ERα and serum OT levels caused by paternal deprivation.     

Peripheral oxytocin in female baboons relates to estrous state and maintenance of sexual consortships

The neuro-hypophysial hormone oxytocin (OT) has been implicated in female reproductive and maternal behaviors and in the formation of pair bonds in monogamous species. Here we measure variation in urinary OT concentrations in relation to reproductive biology and socio-sexual behavior in a promiscuously breeding species, the chacma baboon (Papio hamadryas ursinus). Subjects were members of a habituated group of baboons in the Okavango Delta, Botswana. We collected behavioral data and urine samples from n = 13 cycling females across their estrous cycles and during and outside short-term, exclusive sexual consortships. Samples were analyzed via enzyme immunoassay (EIA) and we used linear mixed models (LMM) to explore the relationship between peripheral OT and a female's estrous stage and consortship status, her previous reproductive experience and fertility. We also used a Pearson's correlation to examine the relationship between OT concentrations of consorting females and their extent of behavioral coordination with their consort partners. The results of the LMM indicate that only estrous stage had a significant influence on OT levels. Females had higher OT levels during their periovulatory period than during other stages of their estrous cycle. There were no differences in the OT levels between consorting and non-consorting periovulatory females. However, among consorting females, there was a significant positive relationship between urinary OT levels and the maintenance of close proximity between consort partners. Our results suggest that physiological and behavioral changes associated with the initiation and maintenance of short-term inter-sexual relationships in baboons correspond with changes in peripheral OT.     

Parental care in captive red-backed vole (Clethrionomys rutilus)

Parental behavior in ten pairs of male and female red-backed voles, Clethrionomus rutilus, was studied under laboratory conditions. Significant sex differences were found in total time spent in the nest, time spent by adults alone in the nest, grooming time, and nest-building activity; in half of the males under study, the level of paternal care was extremely low. These findings indicate different paternal contributions of female and male red-backed voles into the rearing of young, in agreement with the spatial-ethological structure of populations of this species. Parental behavior of C. rutilus is discussed in comparison with that of other species of the subfamily Microtinae.     

Stress impairs new but not established relationships in seasonally social voles

Affiliative social relationships are impacted by stressors and can shape responses to stress. However, the effects of stress on social relationships in different contexts are not well understood. Meadow voles provide an opportunity to study these effects on peer relationships outside of a reproductive context. In winter months, female meadow voles cohabit with peers of both sexes, and social huddling is facilitated by exposure to short, winter-like day lengths in the lab. We investigated the role of stress and corticosterone (cort) levels in social behavior in short day-housed female meadow voles. A brief forced swim elevated cort levels, and we assessed the effects of this stressor on new and established relationships between females. In pairs formed following exposure to swim stress, the stressor significantly reduced the fraction of huddling time subjects spent with a familiar partner. Swim stress did not affect partner preferences in pairs established prior to the stressor. Finally, we examined fecal glucocorticoid metabolite levels via immunoassay in voles housed under short day (10 h light) versus long day (14 h light) conditions and detected higher glucocorticoid levels in long day-housed voles. These findings support a role for stress regulation in the formation of social relationships in female meadow voles, and are consistent with a potential role for seasonal variation in cort in the behavioral transition from solitary to social. Together they highlight the importance of stress and possibly glucocorticoid signaling for social behavior.