Empathy-like Behaviour Research Articles

Beware of Strangers: Dogs' Empathetic Response to Unknown Humans.

Empathy is a complex cognitive ability that has been studied in many social animals, including dogs. Previous studies have found that dogs would rescue their distressed owner more quickly than a calm owner and that dogs respond physiologically and behaviorally to the sound of crying strangers. However, no studies have explored the empathetic and emotional contagion capabilities of dogs towards strangers in rescue paradigms. In the present study, a stranger was placed behind a clear door and was told to cry (distress) or hum (neutral). The dogs' door opening, stress behaviors, tone of approach, and physiological responses were measured. Dogs did not open more frequently or more quickly for the stranger in the distressed condition compared to the neutral condition. Additionally, there was no significant difference between the behavioral or physiological indicators of stress across conditions. It was also found that non-openers were reported by owners to have more fear and, in the empathy test, were more aggressive and fearful in their tone of approach. These results suggest that dogs may be less likely to exhibit empathy-like behaviors to unknown humans in an unfamiliar environment and that owners may be necessary to moderate a dog's stress to show empathetic behaviors.

MDMA enhances empathy-like behaviors in mice via 5-HT release in the nucleus accumbens.

MDMA (3,4-methylenedioxymethamphetamine) is a psychoactive drug with powerful prosocial effects. While MDMA is sometimes termed an "empathogen," empirical studies have struggled to clearly demonstrate these effects or pinpoint underlying mechanisms. Here, we paired the social transfer of pain and analgesia-behavioral tests modeling empathy in mice-with region-specific neuropharmacology, optogenetics, and transgenic manipulations to explore MDMA's action as an empathogen. We report that MDMA, given intraperitoneally or infused directly into the nucleus accumbens (NAc), robustly enhances the social transfer of pain and analgesia. Optogenetic stimulation of 5-HT release in the NAc recapitulates the effects of MDMA, implicating 5-HT signaling as a core mechanism. Last, we demonstrate that systemic MDMA or optogenetic stimulation of NAc 5-HT inputs restores deficits in empathy-like behaviors in the Shank3-deficient mouse model of autism. These findings demonstrate enhancement of empathy-related behaviors by MDMA and implicate 5-HT signaling in the NAc as a core mechanism mediating MDMA's empathogenic effects.

Revisiting Panksepp: a review of his contributions to neuropsychoanalysis

IntroductionPanksepp paved the way for neuropsychoanalysts to better delineate the differences between emotions, feelings, and affect, and their evolutionary purposes. Affect pertains to an individual’s capacity to engage in emotional responses to stimuli, events, memories, and thoughts, while feelings denote the conscious perceptions of emotions, which are primarily social in nature.Feelings are personal and biographical, while affect remains largely impersonal. Panksepp’s theory of basic affective systems in mammals, dividing emotions into positive and negative categories, is another major contribution to neuropsychoanalysis. Three primary emotions -joy, fear, and disgust- have been identified in humans, which are associated with specific peptides and monoamines (e.g., dopamine and endorphins for joy, norepinephrine and CRH for fear, serotonin and substance P for disgust). These basic emotions are thought to have evolved to address basic life tasks in a phylogenetic and ontogenetic primary stage.ObjectivesThis study aims to provide an overview of Jaak Panksepp’s theories and assertions on the journal Neuropsychoanalysis.MethodsThe authors employed a neuropsychoanalytic approach to analyse articles published in the Neuropsychoanalysis journal between 2015-2023.ResultsEmotions primarily function to maintain homeostasis and protect the organism, as in fight or flight responses. In social animals, emotions can sometimes be recognized among individuals of the same and different species. The neurobiological basis of emotional transfer and empathy-like behaviors shed light on cross-species emotion transfer.ConclusionsThe facial feedback hypothesis and the interoceptive inference theory are also discussed as examples of theories for the recognition of emotions as well as the neural mechanisms involved in emotion perception and recognition.Jaak Panksepp’s valuable insights shed light on the mysteries of human affect, and lay the foundation for future work in the field.Disclosure of InterestNone Declared

Examination of empathy-like behaviour in nicotine-preferring rat lines

Aim Addiction is an important global health issue, impacting also addicts environment and society. Empathy plays crucial role in establishing successful social relationships and is a fundamental component of social life. The aim of this study is to investigate how nicotine preferring (NP) strain and oral forced nicotine administration affects empathy-like behaviour in rats, with gender differences. Materials and Methods Sprague-Dawley NP rats (10 males/10 females) and wild-type control rats (10 males/10 females) were used. Behavioural tests were administered to all rats before and after oral forced nicotine administration. The behavioural tests were completed in the fourth week of nicotine administration. Anxiety levels that could affect empathy-like behaviour were evaluated with open field, elevated plus maze tests and with blood cortisol levels. Oxytocin receptor and arginine vasopressin (AVP) levels, which have been shown to be related to empathy-like behaviour, were examined in the prefrontal cortex and amygdala regions using the enzyme-linked immunoassay method. Results It was observed that males from the NP strain showed less empathy-like behaviour than all other groups, and nicotine administration did not cause a significant change in the results. Higher levels of locomotor activity (LA) were found in control females than in all other groups. Blood nicotine and corticosterone levels were higher in NP rats. No significant differences were found in AVP and oxytocin receptor levels in the prefrontal cortex and amygdala. Conclusions It was found that coming from an addicted strain particularly reduces empathy-like behaviour in males.

Neurobehavioral and inflammatory responses following traumatic brain injury in male and female mice

Traumatic brain injury (TBI) is a leading cause of mortality and is associated with a high rate of functional comorbidities, including motor, cognitive, anxiety, depression, and emotional disorders. TBI pathophysiology and recovery are complicated and involve several mechanistic pathways that control neurobehavioral outcomes. In this study, male and female C57Bl/6 J mice were subjected to a controlled cortical impact model of TBI or sham injury and evaluated for different neurobehavioral and inflammatory outcomes over a month. We demonstrate that TBI mice have increased motor dysfunction at early and late time points following the injury as compared to the sham group. Anxiety-like symptoms were time- and task-dependent, with both sexes having increased anxiety-like behavior 2 weeks post-injury. Cognitive functions measured by T-maze presented greater deficits in TBI mice, while there was no sex or injury-related difference in depressive-like behaviors. Notably, a significant effect of sex was found in empathy-like behavior, with females showing more allogrooming and freezing behavior in the consoling and fear observational tests, respectively. Evaluating the impact of the injury-induced brain damage demonstrated a greater injury volume and neuronal degeneration in males compared to females one month after TBI. Moreover, male mice showed higher peripheral inflammatory responses, as represented by elevated serum levels of peripheral leukocytes and inflammatory markers. These results will have significant implications for understanding TBI's long-term consequences on neurobehavioral and inflammatory responses, which are sex-specific and can be considered for individualized therapeutic strategies in treating TBI.

The ameliorative effect of midazolam on empathy-like behavior in old rats.

Although studies suggest that cognitive functions in the elderly are impaired, elderly people tend to be more successful and wiser in solving emotional problems. In empathy-like behavior models, the observer rat rescues the distressed cage mate by displaying emotional and cognitive ability. The aim of the study was to investigate the changes in empathy-like behavior in older rats in comparison to adult rats. In addition, we wanted to determine the effects of alterations in neurochemicals (such as corticosterone, oxytocin, vasopressin, and their receptor levels) and emotional situations on this behavior. In our study, we initially completed empathy-like behavior tests and emotional tests (open field, elevated plus maze) and performed neurochemical examinations in the serum and brain tissues. In the second step of research, we applied a midazolam (benzodiazepine) treatment to examine the effect of anxiety on empathy-like behavior. In the old rats, we observed that empathy-like behavior deteriorated, and anxiety signs were more pronounced. We detected a positive correlation between the latency in empathy-like behavior and corticosterone levels and v1b receptor levels. The midazolam effect on empathy-like behavior was attenuated by flumazenil (a benzodiazepine receptor antagonist). The recordings of ultrasonic vocalization showed frequencies around 50kHz emitted by the observer and this was associated with the expectation of social contact. Our results state that compared to adult rats, old rats were more concerned and failed during empathy-like behavior. Midazolam may improve this behavior by anxiolysis.

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.

Anterior cingulate cortex, but not amygdala, modulates the anxiogenesis induced by living with conspecifics subjected to chronic restraint stress in male mice.

Cohabitation with a partner undergoing chronic restraint stress (CRE) induces anxiogenic-like behaviors through emotional contagion. We hypothesized that the anterior cingulate cortex (ACC) and the amygdala would be involved in the modulation of this emotional process. This study investigated the role of the ACC and amygdala in empathy-like behavior (e.g., anxiety-like responses) induced by living with a mouse subjected to CRE. Male Swiss mice were housed in pairs for 14 days and then allocated into two groups: cagemate stress (one animal of the pair was subjected to 14 days of restraint stress) and cagemate control (no animal experienced stress). Twenty-four hours after the last stress session, cagemates had their brains removed for recording FosB labeling in the ACC and amygdala (Exp.1). In experiments 2 and 3, 24 h after the last stress session, the cagemates received 0.1 μL of saline or cobalt chloride (CoCl2 1 mM) into the ACC or amygdala, and then exposed to the elevated plus-maze (EPM) for recording anxiety. Results showed a decrease of FosB labeling in the ACC without changing immunofluorescence in the amygdala of stress cagemate mice. Cohabitation with mice subjected to CRE provoked anxiogenic-like behaviors. Local inactivation of ACC (but not the amygdala) reversed the anxiogenic-like effects induced by cohabitation with a partner undergoing CRE. These results suggest the involvement of ACC, but not the amygdala, in anxiety induced by emotional contagion.

Assessment of Empathy-Like Behavior in Valproic Acid Induced Rat Model of Autism

Assessment of Empathy-Like Behavior in Valproic Acid Induced Rat Model of Autism

Dissecting social decision-making: A spotlight on oxytocinergic transmission.

Social decision-making requires the ability to balance both the interests of the self and the interests of others to survive in social environments. Empathy is essential to the regulation of this type of interaction, and it often sustains relevant prosocial behaviors such as altruism and helping behavior. In the last decade, our capacity to assess affective and empathy-like behaviors in rodents has expanded our understanding of the neurobiological substrates that underly social decision-making processes such as prosocial behaviors. Within this context, oxytocinergic transmission is profoundly implicated in modulating some of the major components of social decision-making. Thus, this review will present evidence of the association between oxytocin and empathy-like and prosocial behaviors in nonhuman animals. Then, we will dissect the involvement of oxytocinergic transmission-across different brain regions and pathways-in some of the key elements of social decision-making such as emotional discrimination, social recognition, emotional contagion, social dominance, and social memory. Evidence of the modulatory role of oxytocin on social decision-making has raised considerable interest in its clinical relevance, therefore we will also discuss the controversial findings on intranasal oxytocin administration.

Socially Transferred Stress Experience Modulates Social Affective Behaviors in Rats

Social communication of affective states between individuals, as well as actual experiences, influences their internal states and behaviors. Although prior stress experiences promote empathy-like behaviors, it remains unclear whether the social transmission of stress events modulates these behaviors. Here, we provide evidence that transferred stress experiences from cage mates modulate socioaffective approach-avoidance behaviors in rats. Male Wistar-Imamichi rats were assigned to one of five experimental groups (Control (n = 15); no shock with shocked cage mates (n = 15); low (0.1 mA, n = 15), middle (0.5 mA, n = 14), and high shock (1.0 mA, n = 14)). Except for the naïve and housed with stressed mate groups, rats received two foot-shocks (5 s for each). The next day, the subjects were allowed to explore two unfamiliar conspecifics; one was a naïve, while the other was a distressed conspecific that received two foot-shocks (1.0 mA, 5 s) immediately before the test. Rats that were housed with stressed mates, as well as those that experienced a higher intensity of foot-shocks, were more likely to approach, while naïve rats avoided, a distressed conspecific. These results suggest that socially transferred stress shifts socioaffective response styles from avoidance to approach toward a stressed conspecific in rats.

Autism Spectrum Disorder Model Mice Induced by Prenatal Exposure to Valproic Acid Exhibit Enhanced Empathy-Like Behavior via Oxytocinergic Signaling.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by core symptoms, including impairments in social behavior and repetitive interests. Recent studies have revealed that individuals with ASD also display decreased empathy, ultimately leading to difficulties in social relationships; however, another report indicated that individuals with ASD have enhanced emotional empathy. Nonetheless, the neurobiological mechanisms underlying altered empathy in individuals with ASD remain unclear. In this study, we assessed empathy-like behaviors in valproic acid (VPA)-treated mice-a mouse model of ASD with observational fear learning. We then investigated the brain regions and signaling systems responsible for the altered empathy-like behaviors in VPA-treated mice. As a result, mice prenatally exposed to VPA displayed increased empathy-like behaviors, which were not attributed to altered sensitivity to auditory stimuli or enhanced memory for pain-related contexts. Immunohistochemical analysis revealed that the number of c-Fos positive oxytocinergic neurons in the paraventricular nucleus of the hypothalamus (PVN) was significantly higher in VPA-treated mice after observational fear learning. Finally, we found that pretreatment with L-368899, an antagonist of the oxytocin receptor, repressed the empathetic behavior in VPA-treated mice. These results suggest that VPA-treated ASD model animals showed increased emotional empathy-like behaviors through the hyperactivation of PVN oxytocinergic neurons for the first time. Further investigation of this hyperactivity will help to identify extrinsic stimuli and the condition which are capable of activation of PVN oxytocinergic neurons and to identify novel approach to enhance oxytocin signaling, which ultimately pave the way to development of novel therapy for ASD.

NAc-VTA circuit underlies emotional stress-induced anxiety-like behavior in the three-chamber vicarious social defeat stress mouse model

Emotional stress is considered a severe pathogenetic factor of psychiatric disorders. However, the circuit mechanisms remain largely unclear. Using a three-chamber vicarious social defeat stress (3C-VSDS) model in mice, we here show that chronic emotional stress (CES) induces anxiety-like behavior and transient social interaction changes. Dopaminergic neurons of ventral tegmental area (VTA) are required to control this behavioral deficit. VTA dopaminergic neuron hyperactivity induced by CES is involved in the anxiety-like behavior in the innate anxiogenic environment. Chemogenetic activation of VTA dopaminergic neurons directly triggers anxiety-like behavior, while chemogenetic inhibition of these neurons promotes resilience to the CES-induced anxiety-like behavior. Moreover, VTA dopaminergic neurons receiving nucleus accumbens (NAc) projections are activated in CES mice. Bidirectional modulation of the NAc-VTA circuit mimics or reverses the CES-induced anxiety-like behavior. In conclusion, we propose that a NAc-VTA circuit critically establishes and regulates the CES-induced anxiety-like behavior. This study not only characterizes a preclinical model that is representative of the nuanced aspect of CES, but also provides insight to the circuit-level neuronal processes that underlie empathy-like behavior.

The effects of chronic restraint stress on empathy-like behaviour in rats

It is clearly known that psychological stress is an important threat to health in today's modern societies. Recent studies have shown that acute stress causes an increase in positive social behaviours such as prosocial behaviour and devotion which are components of empathic behaviour. Neuropsychiatric manifestations such as anxiety and depression may affect empathic behaviour. The aim of this study was to investigate the effects of chronic restraint stress on empathy-like behaviour and the histopathological changes in the amygdala, prefrontal cortex in the adrenal glands and thymus, as well as the neurochemical pathways associated with empathy, oxytocin and vasopressin. The chronic stress group was subjected to restraint stress daily for 14 days after all subjects were trained to rescue its stressed cagemate using empathy test equipment for 12 days. It was observed that chronic restraint stress had no effect on empathy-like behaviour in rats. Vasopressin levels in amygdala was increased in chronic stress group compared to control group. Anxiety and depression indicators did not change in both groups. In the open field test, control group spent more time in thigmo zone compared to chronic stress group. Adrenal glands relative weights and apoptotic cell ratios were significantly higher in the chronic stress group compared to the control group (expectedly). Although there was no significant difference in behavioral tests, histopathological changes were detected. In subsequent studies, it is appropriate to examine the effects of different types of stress applications, gender-related changes, and other neurochemical pathways associated with stress and empathy.

5-HT3 receptor within the amygdaloid complex modulates pain hypersensitivity induced by empathy model of cohabitation with a partner in chronic pain condition in mice

ABSTRACT Cohabitation with a partner undergoing chronic pain induces pain hypersensitivity. Among a lot of other neurochemical pathways, the serotonin (5-HT) role, specifically the 5-HT3 receptor (5-HT3R), in the amygdala has never been evaluated in this model. Here we studied the effects of the amygdala’s chemical inhibition, its neuronal activation pattern, and 5-HT, 5-HIAA, and 5-HT turnover within the amygdala. Furthermore, the systemic and intra-amygdala 5-HT3R activation and blockade in mice that cohabited with a conspecific subjected to chronic constriction injury were investigated. Male Swiss mice were housed in partners for 28 days. The dyads were divided into two groups on the 14th day: cagemate nerve constriction (CNC) and cagemate sham (CS). On the 24th day, cagemates underwent a stereotaxic surgery (when necessary) and, on the 28th day, they were evaluated on the writhing test. The amygdala inactivation promotes pain-hypersensitivity behaviors in groups and dyads; cohabitation with a partner with chronic pain did not change FosB-labeled cells in the amygdala’s nucleus and increases 5-HT turnover in cagemates. Systemic and intra-amygdala 5-HT3R activation attenuated and enhanced the number of writhes, respectively. In contrast, 5-HT3R blockade reduced hypersensitivity pain response. Results suggest the involvement of amygdala serotonergic signaling via 5-HT3R in empathy-like behavior.

Quality of early-life maternal care predicts empathy-like behavior in adult male rats: Linking empathy to BDNF gene expression in associated brain regions

Empathy is the ability to experience a shared affective state as others. It enhances group living and manifests itself as helping behavior towards a distressed person. It also can flourish by nurturing. Recent findings suggest that rodents exhibit empathy-like behavior towards their conspecifics. However, the role of early-life experiences (e.g., maternal care) is not clear on the development of empathy-like behavior. Moreover, brain-derived neutrophilic factor (BDNF) is a pivotal protein in modulating the brain's function and behaviors. Evidence suggests that the expression of the BDNF gene can be affected by the quality of maternal care. In this study, we questioned whether variation in maternal care modulates empathy-like behavior of male rats in adulthood. Additionally, gene expression of BDNF was measured in the amygdala, hippocampus, insula, anterior cingulate cortex, prefrontal cortex, and striatum in these adult male rats. Based on the pattern of maternal care, the offspring were divided into high maternal care (HMC) and low maternal care (LMC) groups. We confirmed that the early-life experience of HMC significantly promoted the empathy-like behavior of rats in adulthood compared to LMC. In terms of gene expression, the HMC group consistently had higher BDNF gene expression in all studied regions, except anterior cingulate cortex which groups were not different. Taken together, it suggests that maternal care in infancy predicts empathy-like behavior in adulthood and differences in BDNF gene expression in different brain regions may reflect the underlying mechanism.

Conformity-like behaviour in mice observing the freezing of other mice: a model of empathy

BackgroundEmpathy refers to the ability to recognise and share emotions with others. Several research groups have recognised observational fear in mice as a useful behavioural model for assessing their ability to empathise. However, in these observation systems, it remains unclear whether the observer mouse truly recognises the movements of, and empathises with, the demonstrator mouse. We examined changes in the behaviour of an observer mouse when a demonstrator mouse was anaesthetised, when the demonstrator’s activity was increased, and when the interval of electrical stimulation was altered. If mice exhibit an ability to empathise, then the observer should display empathic behaviour when the demonstrator experiences pain or discomfort under any circumstances.ResultsRelative to low-frequency stimulation, frequent electrical stimulation reduced immobility time among observer mice. Moreover, when demonstrators exhibited excessive activity, the activity of the observers significantly increased. In addition, the proportion of immobility time among observer mice significantly increased when demonstrator mice exhibited fear learning and excessive immobility.ConclusionAlthough our results indicate that observer mice change their behaviour based on the movements of demonstrator mice, increases in immobility time may reflect conformity-like behaviour rather than emotional empathy. Thus, not only visual but also auditory and odour information additionally influenced the conformity-like behaviour shown by observer mice. Thus, our findings suggest that methods other than the fear observation system should be used to investigate rodent empathy-like behaviour.

Nitric oxide modulates cognitive, nociceptive and motor functions in a rat model of empathy

Aim: Empathy is defined as the capability to comprehend and simulate the feelings of others. Though it has been considered as a human feature, recent studies have demonstrated empathy-like behaviors in other animals including rats. The objective of the current study was to evaluate the role of nitric oxide system in cognition and nociception changes following observation of cagemates in pain.Material and methods: Adult male Wistar rats were used (n = 8 for each group). One sibling received formalin injection into the hindpaw five times within a nine-day period and the other sibling observed the pain while being pretreated with saline, L-NAME or L-arginine (10 mg/kg, i.p.). Nociception, anxiety-like behavior and locomotion, balance, muscle strength, spatial and fear learning were evaluated.Results: Observing a family member (sibling) in pain increased anxiety-like behavior, led to a hyperalgesia in the observer and disruption of spatial memory. Nitric oxide system modulated these changes, so that in some paradigms the activation of NO and in some others inhibition of NO dampened the effect of observing pain in a cagemate on the evaluated features.Conclusions: Results in the current study demonstrated a modulating effect of NO on empathy induced changes in nociception, motor function and spatial memory. Further studies addressing the specific brain regions and other neurotransmitters involved are recommended.

Magnesium acetyl taurate prevents tissue damage and deterioration of prosocial behavior related with vasopressin levels in traumatic brain injured rats

To investigate the effects of different magnesium forms on tissue damage, cognitive and emotional behavioural impairment after mild traumatic brain injury (TBI). Rats were divided into 5 groups (control, trauma, magnesium sulphate, magnesium citrate, magnesium acetyl taurate) and following head trauma, empathy-like behaviour, anxiety-like behaviour (elevated plus maze and open field tests), and depression (forced swim test) were measured. The rats were then sacrificed 12 days later. Oxytocin, vasopressin and receptors levels in the amygdala and prefrontal cortex regions were measured. Histopathological damage (with haematoxylin-eosin staining) and apoptosis (with caspase-3 immunohistochemistry) was evaluated. Following head trauma, anxiety-like behaviour and depression tests did not change; empathy-like behaviour deteriorated on the 3rd day and improved gradually on the 6th and 12th days. Oxytocin, vasopressin and vasopressin v1b receptor levels decreased in the amygdala; morphological damage and apoptosis were significant. Magnesium acetyl taurate effectively ameliorated histopathological deteriorations and improved vasopressin and v1b receptor levels in the amygdala. Transient deterioration of empathy-like behaviour was impeded only in magnesium taurate treatment. Magnesium acetyl taurate can be a promising candidate agent to prevent structural and functional damage in traumatic brain injury.

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

BackgroundConsolation 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/ResultsPhysical 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.ConclusionsOur 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.