Effects of paternal deprivation on empathetic behavior and the involvement of oxytocin receptors in the anterior cingulate cortex.

Paternal deprivation (PD) impairs social cognition and sociality and increases levels of anxiety-like behavior. However, whether PD affects the levels of empathy in offspring and its underlying mechanisms remain unknown. The present study found that PD increased anxiety-like behavior in mandarin voles (Microtus mandarinus), impaired sociality, reduced the ability of emotional contagion, and the level of consolation behavior. Meanwhile, PD reduced OT neurons in the paraventricular nucleus (PVN) in both male and female mandarin voles. PD decreased the level of OT receptor (OTR) mRNA in the anterior cingulate cortex (ACC) of male and female mandarin voles. Besides, OTR overexpression in the ACC reversed the PD-induced changes in anxiety-like behavior, social preference, emotional contagion, and consolation behavior. Interference of OTR expression in the ACC increased levels of anxiety-like behaviors, while it reduced levels of sociality, emotional contagion, and consolation. These results revealed that the OTR in the ACC is involved in the effects of PD on empathetic behaviors, and provide mechanistic insight into how social experiences affect empathetic behaviors.

Chronic stress and stressful emotional contagion affect the empathy-like behavior of rats.

Empathy is a potential motivation for prosocial behaviors that is related to many psychiatric diseases, such as major depressive disorder; however, its neural mechanisms remain unclear. To elucidate the relationship between empathy and stress, we established a chronic stress contagion (SC) procedure combined with chronic unpredictable mild stress (CUMS) to investigate (1) whether depressive rats show impaired empathy-like behavior toward fearful conspecifics, (2) whether frequent social contact with normal familiar conspecifics (social support) alleviates the negative effects of CUMS, and (3) the effect of long-term exposure to a depressed partner on emotional and empathic responses in normal rats. We found that the CUMS group showed less empathy-like behavior in the social transfer of fear model (STFM), as indicated by less social interaction with the demonstrator and reduced freezing behavior in the fear-expression test. Social contact partially alleviated depression-like behaviors and the negative effect of CUMS in the fear-transfer test. The normal rats who experienced stress contagion from daily exposure to a depressed partner for 3 weeks showed lower anxiety and increased social response in the fear-transfer test than the control group. We concluded that chronic stress impairs empathy-like behaviors, while social contact partially buffers the effect of CUMS. Thus, social contact or contagion of stress is mutually beneficial to both stressed individuals and nonstressed partners. Higher dopamine and lower norepinephrine levels in the basolateral amygdala probably contributed to these beneficial effects.

Providing or receiving alloparental care promote partner preference and alter central oxytocin and dopamine systems in adult mandarin voles.

Juveniles of cooperative breeding species usually remain in the natal area and provide care to younger siblings, a behavior considered one form of alloparenting in the natural condition. Previous studies have demonstrated the effects of providing or receiving alloparental care on adult behaviors, including anxiety-like behavior, social interaction, and parental behavior, but little is known about the influences on species-typical bonding behaviors, such as pair-bond formation. In this study, we explored this concept using socially monogamous mandarin voles (Lasiopodomys mandarinus). As the oxytocin (OT) and dopamine systems are involved in alloparental and pair-bonding behaviors, we also examined the levels of central OT and tyrosine hydroxylase (TH), as well as OT receptor (OTR) and dopamine D1-type and D2-type receptors (D1R and D2R) mRNA expression in the nucleus accumbens (NAcc) and amygdala to investigate the underlying mechanisms. Our results show that mandarin voles providing alloparental care to younger siblings displayed facilitation of partner preference formation, lower levels of OT expression in the paraventricular nucleus of the hypothalamus (PVN) and lateral hypothalamus (LH), and increased OTR and D2R mRNA expression in the NAcc compared to controls. Individuals receiving alloparental care also demonstrated facilitation of partner preference formation in adult voles. Additionally, alloparental care enhanced OT expression in the PVN, anterior medial preoptic nucleus (MPOAa), medial amygdala (MeA), and TH expression in the ventral tegmental area (VTA) and zona incerta (ZI). Furthermore, males displayed decreased D1R mRNA expression in the NAcc, whereas females showed slightly increased D2R expression in the amygdala. These results demonstrate that providing or received alloparental care can promote partner preference formation in monogamous species and that these changes are associated with altered OT and dopamine levels and their receptors in specific brain regions.

Involvement of Serotonergic Projections from the Dorsal Raphe to the Medial Preoptic Area in the Regulation of the Pup-Directed Paternal Response of Male Mandarin Voles.

Male mammals display different paternal responses to pups, either attacking or killing the young offspring, or contrastingly, caring for them. The neural circuit mechanism underlying the between-individual variation in the pup-directed responsiveness of male mammals remains unclear. Monogamous mandarin voles were used to complete the present study. The male individuals were identified as paternal and infanticidal voles, according their behavioral responses to pups. It was found that the serotonin release in the medial preoptic area (MPOA), as well as the serotonergic neuron activity, significantly increased upon licking the pups, but showed no changes after attacking the pups, as revealed by the in vivo fiber photometry of the fluorescence signal from the 5-HT 1.0 sensor and the calcium imaging indicator, respectively. It was verified that the 5-HTergic neural projections to the MPOA originated mainly from the ventral part of the dorsal raphe (vDR). Furthermore, the chemogenetic inhibition of serotonergic projections from the vDR to the MPOA decreased the paternal behaviors and shortened the latency to attack the pups. In contrast, the activation of serotonergic neurons via optogenetics extended the licking duration and inhibited infanticide. Collectively, these results elucidate that the serotonergic projections from the vDR to the MPOA, a previously unrecognized pathway, regulate the paternal responses of virgin male mandarin voles to pups.

Paraventricular Nucleus Oxytocin Subsystems Promote Active Paternal Behaviors in Mandarin Voles.

Paternal care plays a critical role in the development of brain and behaviors in offspring in monogamous species. However, the neurobiological mechanisms, especially the neuronal circuity, underlying paternal care is largely unknown. Using socially monogamous male mandarin voles (Microtus mandarinus) with high levels of paternal care, we found that paraventricular nucleus of the hypothalamus (PVN) to ventral tegmental area (VTA) or nucleus accumbens (NAc) oxytocin (OT) neurons are activated during paternal care. Chemogenetic activation/inhibition of the PVN OT projection to VTA promoted/decreased paternal care, respectively. Chemogenetic inhibition of the PVN to VTA OT pathway reduced dopamine (DA) release in the NAc of male mandarin voles during licking and grooming of pups as revealed by in vivo fiber photometry. Optogenetic activation/inhibition of the VTA to NAc DA pathway possibly enhanced/suppressed paternal behaviors, respectively. Furthermore, chemogenetic activation/inhibition of PVN to NAc OT circuit enhanced/inhibited paternal care. This finding is a first step toward delineating the neuronal circuity underlying paternal care and may have implications for treating abnormalities in paternal care associated with paternal postpartum depression or paternal abuse.SIGNIFICANCE STATEMENT Paternal behavior is essential for offspring survival and development in some mammalian species. However, the circuit mechanisms underlying the paternal brain are poorly understood. We show that manipulation of paraventricular nucleus of the hypothalamus (PVN) to ventral tegmental area (VTA) oxytocin (OT) projections as well as VTA to nucleus accumbens (NAc) DA projections promote paternal behaviors. Inhibition the PVN to VTA OT pathway reduces DA release in the NAc during pup licking and grooming. PVN to NAc OT circuit is also essential for paternal behaviors. Our findings identify two new neural circuits that modulate paternal behaviors.

The involvement of oxytocin in the effects of chronic social defeat stress on emotional behaviours in adult female mandarin voles.

Chronic social defeat stress (CSDS) can induce anxiety and depression in male rodents, but the prevalence of anxiety and depression is much higher in females, and effects of CSDS on adult females and its underlying mechanism remain unclear. Oxytocin is a stress-buffering hormone in the brain that modulates the physiological effects of stress. Strikingly, research regarding the effect of oxytocin on emotional changes caused by CSDS is still lacking in females. Thus, we focused on the involvement of the oxytocin system in changes in emotional regulation induced by CSDS in female voles. Seventy-day-old female mandarin voles (Microtus mandarinus) were exposed to aggressive adult females for 14 days, and the effects of CSDS on emotion and regulation of oxytocin system were characterized. In addition, we injected vehicle, oxytocin and oxytocin receptor antagonist into the nucleus accumbens (Nacc) of female voles to investigate the involvement of Nacc oxytocin in the effect of CSDS on emotion. Herein, we reported that CSDS increased anxiety and depression-like behaviour and the circulating level of corticosterone, but decreased the number of oxytocin projections and the protein and mRNA expression levels of oxytocin receptor in the Nacc. Injection of oxytocin into the Nacc reversed the effects of CSDS on anxiety-like and depressive-like behaviour, whereas combined injections of oxytocin and oxytocin receptor antagonist eliminated these effects. In conclusion, CSDS increases the levels of anxiety and depression possibly via a reduction in oxytocin projections and the oxytocin receptor level in the Nacc. Nacc oxytocin may be involved in the effects of CSDS on emotional behaviours.

Reduced Consolation Behaviors in Physically Stressed Mandarin Voles: Involvement of Oxytocin, Dopamine D2, and Serotonin 1A Receptors Within the Anterior Cingulate Cortex.

BACKGROUND: Consolation is a type of empathy-like behavior that has recently been observed in some socially living rodents. Despite the growing body of literature suggesting that stress affects empathy, the relationship between stress and consolation remains understudied at the preclinical level. Here, we examined the effects of chronic emotional stress or physical stress exposure on consolation and emotional behaviors by using the socially monogamous mandarin vole (Microtus mandarinus) in both males and females. METHOD/RESULTS: Physical stress voles were exposed to 14-day social defeat stress, whereas emotional stress voles vicariously experienced the defeat of their partners. We found that physical stress, but not emotional stress, voles showed reduced grooming toward their defeated partners and increased anxiety- and despair-like behaviors. Meanwhile, physical stress voles exhibited decreased neural activity in the anterior cingulate cortex, which is centrally involved in empathy. The densities of oxytocin receptors, dopamine D2 receptors, and serotonin 1A-receptors within the anterior cingulate cortex were significantly decreased in the physical stress group compared with controls. All the behavioral and physiological changes were similar between the sexes. Finally, we found that the reduced consolation behavior and some anxiety-like syndromes in physical stress voles could be alleviated by pretreatment with an oxytocin receptor, D2 receptors, or serotonin 1A-receptor agonist within the anterior cingulate cortex, whereas injections of corresponding receptor antagonists to the control voles decreased the consolation behavior and increased some anxiety-like behaviors. CONCLUSIONS: Our results indicated that chronic physical stress exposure impaired consolation and induced anxiety-like behaviors in mandarin voles and oxytocin receptors, 5-HT1A receptors, and D2 receptors within the anterior cingulate cortex may play important roles in these processes.

Preweaning Paternal Deprivation Impacts Parental Responses to Pups and Alters the Serum Oxytocin and Corticosterone Levels and Oxytocin Receptor, Vasopressin 1A Receptor, Oestrogen Receptor, Dopamine Type I Receptor, Dopamine Type II Receptor Levels in Relevant Brain Regions in Adult Mandarin Voles.

Although maternal separation and neonatal paternal deprivation (PD) have been found to exert a profound and persistent effects on the physiological and behavioural development of offspring, whether preweaning PD (PPD; from PND 10 to 21) affects maternal and parental responses to pups and the underlying neuroendocrine mechanism are under-investigated. Using monogamous mandarin voles (Microtus mandarinus), the present study found that PPD increased the latency to approach a pup-containing ball, decreased the total durations of sniffing and contacting a pup-containing ball and walking and increased the total duration of inactivity in both sexes. Moreover, PPD decreased serum oxytocin levels and increased corticosterone levels, but only in females. Furthermore, in both males and females, PPD decreased the expression of oxytocin receptor mRNA and protein in the medial preoptic area (MPOA), nucleus accumbens (NAcc) and medial prefrontal cortex (mPFC), but increased it in the medial amygdala (MeA) and decreased the expression of oestrogen receptor mRNA and protein in the MPOA. PPD increased the expression of dopamine type I receptor in the NAcc, but decreased it in the mPFC. PPD decreased dopamine type II receptor (D2R) in the NAcc both in males and females, but increased D2R in the mPFC in females and decreased D2R protein expression in males. Moreover, PPD decreased vasopressin 1A receptor (V1AR) in the MPOA, MeA and mPFC, but only in males. Our results suggest that the reduction of parental responses to pups induced by PPD may be associated with the sex-specific alteration of several neuroendocrine parameters in relevant brain regions.

Serotonin Signaling Trough Prelimbic 5-HT1A Receptors Modulates CSDS-Induced Behavioral Changes in Adult Female Voles.

BACKGROUND: Most previous studies have focused on the effects of social defeat in male juvenile individuals. Whether chronic social defeat stress in adulthood affects female emotion and the underlying mechanisms remains unclear. METHODS: Using highly aggressive adult female mandarin voles (Microtus mandarinus), the present study aimed to determine the effects of chronic social defeat stress on anxiety- and depression-like behaviors in adult female rodents and investigate the neurobiological mechanisms underlying these effects. RESULTS: Exposure of adult female voles to social defeat stress for 14 days reduced the time spent in the central area of the open field test and in the open arms of the elevated plus maze and lengthened the immobility time in the tail suspension and forced swimming tests, indicating increased anxiety- and depression-like behaviors. Meanwhile, defeated voles exhibited increased neural activity in the prelimbic cortex of the medial prefrontal cortex. Furthermore, chronic social defeat stress reduced serotonin projections and levels of serotonin 1A receptors in the medial prefrontal cortex-prelimbic cortex. Intra-prelimbic cortex microinjections of the serotonin 1A receptor agonist 8-OH-DPAT reversed the alterations in emotional behaviors, whereas injections of the serotonin 1A receptor antagonist WAY-100635 into the prelimbic cortex of control voles increased the levels of anxiety- and depression-like behaviors. CONCLUSIONS: Taken together, our results demonstrated that chronic social defeat stress increased anxiety- and depression-like behaviors in adult female voles, and these effects were mediated by the action of serotonin on the serotonin 1A receptors in the prelimbic cortex. The serotonin system may be a promising target to treat emotional disorders induced by chronic social defeat stress.

Role of oxytocin in the medial preoptic area (MPOA) in the modulation of paternal behavior in mandarin voles.

Parental care plays an important role in individual survival and development in mammals. Many studies have focused on the mechanisms underlying maternal behavior. However, the underlying neural mechanisms of paternal behavior are less understood. Using monogamous mandarin voles (Microtus mandarinus), the present study found that fathers initiated more paternal behavior and the virgin male showed more infanticide. Moreover fathers had shorter latency to approach a pup at the postnatal day (PND) 10 than PND1, PND20 than nonfathers. Fathers had a shorter latency to take care of unfamiliar pups than nonfathers. They had higher levels of paternal behavior at PND 10 than PND1 and PND20 toward the mandarin vole pups. Fathers had a significantly higher serum concentration of oxytocin (OT) than virgin males. Both RT-PCR and Western blot results indicated that the levels of the oxytocin receptor (OTR) in the medial preoptic area (MPOA) of fathers were significantly higher than in virgin males, but the levels of vasopressin 1a receptor (V1AR) mRNA and protein expression in the MPOA did not show significant differences. Microinjection of an oxytocin receptor antagonist into the MPOA significantly reduced the total duration of paternal behavior and increased the latency to approach the pup and initiate paternal behavior. Our results indicated that OT plays a key role in the modulation of paternal behavior via the MPOA.

Pre-weaning paternal deprivation impairs social recognition and alters hippocampal neurogenesis and spine density in adult mandarin voles.

Disruption of the early social environment, such as maternal separation or early deprivation, can impair cognitive function, alter offspring neurogenesis and restrict dendritic architecture in the hippocampus. However, whether paternal deprivation during the pre-weaning period affects adult neurogenesis, synaptogenesis and social recognition remains unclear in monogamous species. In the present study, mandarin vole (Microtus mandarinus) pups were deprived of fathers during postnatal day 14-21. Then social recognition, hippocampal neurogenesis and spine density, basal levels of corticosterone (CORT) and oxytocin (OT) were examined at adulthood. We found that paternal deprivation impaired social recognition at adulthood. In addition, paternal deprivation significantly reduced 5-bromo-2-deoxyuidine (BrdU) immunoreactive cells (p < 0.01) and Brdu/Neun-labeled cells (p < 0.05) in the dentate gyrus compared to those of biparental care group in females, but not in males (p > 0.05). Meanwhile, paternal deprivation group had fewer double-staining cells with BrdU and the immature neuron marker doublecortin than biparental care group both in male (p < 0.01) and female (p < 0.05) voles. Paternal deprivation also decreased the number of dendritic spines in the dentate gyrus at adulthood. Paternal deprivation reduced circulating levels of OT and increased CORT only in females. These results demonstrated that impaired social recognition induced by paternal deprivation may be linked with alterations in neurogenesis and spine densityof the dentate gyrus and levels of OT and CORT, especially in females.

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.

Different behavioral, neural and neuropeptide responses of fathers to their own and to alien pups in mandarin voles.

Mothers often prefer to care for their own offspring rather than those of other females. However, whether fathers respond differently to their own pups and to alien ones remains unclear. In this study, we found that male mandarin voles (Microtus mandarinus) directed more sniffing toward their own pups than toward alien pups. The numbers of Fos-immunoreactive neurons in the medial preoptic nucleus, bed nucleus of the stria terminalis, nucleus accumbens, anterior cingulate cortex were significantly increased when fathers were exposed to an alien pups; however, more brain regions such as paraventricular nucleus, hypothalamic supraoptic nucleus, lateral habenula, ventral lateral septal nucleus, and medial amygdaloid nucleus showed increased number of Fos-immunoreactive neurons activated when the fathers were exposed to their own pups. Exposure to their own pups also induced a greater number of Fos-immunoreactive neurons in the anterior cingulate cortex, paraventricular nucleus, hypothalamic supraoptic nucleus, lateral habenula, ventral lateral septal nucleus and medial amygdaloid nucleus, as well as higher expression of oxytocin and vasopressin in the paraventricular nucleus, compared with exposure to alien pups. Our results indicated that fathers demonstrated different behavioral and neural responses to their own and to alien pups.

Bilobalide alleviates depression-like behavior and cognitive deficit induced by chronic unpredictable mild stress in mice.

Bilobalide (BB), a unique constituent of Ginkgo biloba, has powerful neuroprotection and stress-alleviating properties. However, whether BB exerts a positive effect on depression and cognitive deficit induced by chronic stress is not known. The present study was designed to investigate the influence of BB on depression and cognitive impairments induced by chronic unpredictable mild stress (CUMS) in mice. During daily exposure to stressors for 5 consecutive weeks, mice were administered BB at the doses of 0, 3, or 6 mg/kg/day intraperitoneally. We replicated the finding that CUMS induced depression-like behavior and cognitive deficits as the CUMS+vehicle (VEH) group showed a significant increase in immobility in the tail suspension test, a decrease in the discrimination index of the novel object recognition task, and increased latency to platform and decreased number of platform crossings in the Morris water maze compared with the control+VEH group. Chronic administration of BB effectively reversed these alterations. In addition, the CUMS+VEH group showed significantly higher levels of baseline serum corticosterone than those of the control+VEH group and BB dose-dependently inhibited this effect. Our results suggest that BB may be useful for inhibition of depression-like behavior and cognitive deficits, and this protective effect was possibly exerted partly through an action on the hypothalamic-pituitary-adrenal axis.

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.

Early bi-parental separation or neonatal paternal deprivation in mandarin voles reduces adult offspring paternal behavior and alters serum corticosterone levels and neurochemistry.

Although the effect of early social environments on maternal care in adulthood has been examined in detail, few studies have addressed the long-term effect on paternal care and its underlying neuroendocrine mechanisms. Here, using monogamous mandarin voles (Microtus mandarinus) that show high levels of paternal care, the effects of early bi-parental separation (EBPS) or neonatal paternal deprivation (NPD) on adult paternal behavior, serum corticosterone levels, and receptor mRNA expression in the nucleus accumbens (NAcc) and medial preoptic area (MPOA) were investigated. Compared to the parental care group (PC), we found that EBPS reduced crouching behavior and increased inactivity, self-grooming, and serum corticosterone levels in adult offspring; and NPD significantly reduced retrieval behavior and increased self-grooming behavior of offspring at adulthood. EBPS displayed more dopamine type I receptor (D1R) mRNA expression in the NAcc, but less oxytocin receptor (OTR) mRNA expression than PC in the MPOA. Both EBPS and NPD exhibited more mRNA expression of estrogen receptor alpha (ERα) than PC in the MPOA. In the EBPS group, increased serum corticosterone concentration was closely associated with reduced crouching behavior, and reduced expression of OTR was closely associated with altered crouching behavior and increased D1R expression. Our results provide substantial evidence that EBPS or NPD has long-term consequences and reduces paternal behavior in adult animals. Importantly the oxytocin system in the MPOA might interact with NAcc dopamine systems to regulate paternal behavior and EBPS may affect interactions between the MPOA and NAcc.

Behavioral responses to pups in males with different reproductive experiences are associated with changes in central OT, TH and OTR, D1R, D2R mRNA expression in mandarin voles.

Male rodents behave differently toward pups because of different sexual and/or paternal experiences; however, the mechanisms underlying these responses are not well understood. Using socially monogamous mandarin voles (Microtus mandarinus) we investigated the behavioral responses of males with different reproductive experiences (virgin males, paired males and new fathers) to new born pups. Central levels of neuropeptide oxytocin (OT), tyrosine hydroxylase (TH), as well as oxytocin receptor (OTR), dopamine 1-type receptor (D1R) and dopamine 2-type receptor (D2R) mRNA expression in the nucleus accumbens and medial amygdala were also measured in these males. Our data showed that new fathers exhibited more approaching behavior and contained more OT-immunoreactive and TH-immunoreactive neurons. In addition to increased OTR mRNA expression in the nucleus accumbens and medial amygdala, new fathers had higher D1R and D2R mRNA expression in the nucleus accumbens, and less D1R and D2R mRNA expression in the medial amygdala than paired males. These results demonstrate that males with different reproductive experiences display different behavioral responses to pups and that these differences are associated with altered OT and dopamine, and their receptors in specific brain regions.

Sociality and oxytocin and vasopressin in the brain of male and female dominant and subordinate mandarin voles.

The dominant-subordinate hierarchy in animals often needs to be established via agonistic encounters and consequently affects reproduction and survival. Differences in brain neuropeptides and sociality among dominant and subordinate males and females remain poorly understood. Here we explore neuropeptide levels and sociality during agonistic encounter tests in mandarin voles. We found that dominant mandarin voles engaged in higher levels of approaching, investigating, self-grooming and exploring behavior than subordinates. Dominant males habituated better to a stimulus vole than dominant females. Dominant males displayed significantly less oxytocin-immunoreactive neurons in the paraventricular nuclei and more vasopressin-immunoreactive neurons in the paraventricular nuclei, supraoptic nuclei, and the lateral and anterior hypothalamus than subordinates. Dominant females displayed significantly more vasopressin-immunoreactive neurons in the lateral hypothalamus and anterior hypothalamus than subordinates. Sex differences were found in the level of oxytocin and vasopressin. These results indicate that distinct parameters related to central nervous oxytocin and vasopressin are associated with behaviors during agonistic encounters in a sex-specific manner in mandarin voles.

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.

Early paternal deprivation alters levels of hippocampal brain-derived neurotrophic factor and glucocorticoid receptor and serum corticosterone and adrenocorticotropin in a sex-specific way in socially monogamous mandarin voles.

In monogamous mammals, fathers play an important role in the development of the brain and typical behavior in offspring, but the exact nature of this process is not well understood. In particular, little research has addressed whether the presence or absence of paternal care alters levels of hippocampal glucocorticoid receptor (GR) and brain-derived neurotrophic factor (BDNF), and basal levels of serum corticosterone (CORT) and adrenocorticotropin (ACTH). Here, we explored this concept using socially monogamous mandarin voles (Microtus mandarinus), a species in which fathers display high levels of paternal care toward their pups. Our immunohistochemical study shows that paternal deprivation (PD) significantly decreased levels of GR and BDNF protein in the CA1 and CA2/3 of the hippocampus. In the dental gyrus, decreases in GR and BDNF induced by PD were evident in females but not in males. Additionally, enzyme-linked immunosorbent assay results show that PD significantly upregulated levels of serum CORT and ACTH in females, but not males. These findings demonstrate that PD alters HPA axis activity in a sex-specific way. The changes in stress hormones documented here may be associated with alteration in hippocampal BDNF and GR levels.