Unfamiliar Mice Research Articles

Molecular hydrogen supplementation in mice ameliorates lipopolysaccharide-induced loss of interest.

The objective of this study was to evaluate the potential of hydrogen in preventing and treating psychiatric symptoms, particularly depressed mood and loss of interest, and to explore its underlying mechanisms. A mouse model exhibiting inflammation-derived depressive symptoms was used for the investigation. Institute of Cancer Research mice were subjected to a 7-day intervention of either 30% hydrogen or 40 g per day of air via jelly intake. On the final day, lipopolysaccharide (LPS) was intraperitoneally administered at 5 mg/kg to induce inflammation-related depressive symptoms. Behavioral and biochemical assessments were conducted 24 h post-LPS administration. Following LPS administration, a decrease in spontaneous behavior was observed; however, this effect was mitigated in the group treated with hydrogen. The social interaction test revealed a significant reduction in interactions with unfamiliar mice in the LPS-treated group, whereas the hydrogen-treated group exhibited no such decrease. No significant changes were noted in the forced-swim test for either group. Additionally, the administration of LPS in the hydrogen group did not result in a decrease in zonula occludens-1, a biochemical marker associated with barrier function at the cerebrovascular barrier and expressed in tight junctions. Hydrogen administration demonstrated a preventive effect against the LPS-induced loss of interest, suggesting a potential role in symptom prevention. However, it did not exhibit a suppressive effect on depressive symptoms in this particular model. These findings highlight the nuanced impact of hydrogen in the context of inflammation-induced psychiatric symptoms, indicating potential avenues for further exploration and research.

Sex and stress interactions in fear synchrony of mouse dyads.

Socially coordinated threat responses support the survival of animal groups. Given their distinct social roles, males and females must differ in such coordination. Here, we report such differences during the synchronization of auditory-conditioned freezing in mouse dyads. To study the interaction of emotional states with social cues underlying synchronization, we modulated emotional states with prior stress or modified the social cues by pairing unfamiliar or opposite-sex mice. In same-sex dyads, males exhibited more robust synchrony than females. Stress disrupted male synchrony in a prefrontal cortex-dependent manner but enhanced it in females. Unfamiliarity moderately reduced synchrony in males but not in females. In dyads with opposite-sex partners, fear synchrony was resilient to both stress and unfamiliarity. Decomposing the synchronization process in the same-sex dyads revealed sex-specific behavioral strategies correlated with synchrony magnitude: following partners' state transitions in males and retroacting synchrony-breaking actions in females. Those were altered by stress and unfamiliarity. The opposite-sex dyads exhibited no synchrony-correlated strategy. These findings reveal sex-specific adaptations of socio-emotional integration defining coordinated behavior and suggest that sex-recognition circuits confer resilience to stress and unfamiliarity in opposite-sex dyads.

Differences in physiology and behavior between male winner and loser mice in the tube test

Social hierarchy is a crucial element for survival, reproduction, fitness, and the maintenance of a stable social group in social animals. This study aimed to investigate the physiological indicators, nociception, unfamiliar female mice preference, spatial learning memory, and contextual fear memory of male mice with different social status in the same cage. Our findings revealed significant differences in the trunk temperature and contextual fear memory between winner and loser mice. However, there were no major discrepancies in body weight, random and fasting blood glucose levels, whisker number, frontal and perianal temperature, spleen size, mechanical and thermal pain thresholds, preference for unfamiliar female mice, and spatial memory. In conclusion, social status can affect mice in multiple ways, and, therefore, its influence should be considered when conducting studies using these animals.

Mice Recognise Mice in Neighbouring Rearing Cages and Change Their Social Behaviour.

Mice are social animals that change their behaviour primarily in response to visual, olfactory, and auditory information from conspecifics. Rearing conditions such as cage size and colour are important factors influencing mouse behaviour. In recent years, transparent plastic cages have become standard breeding cages. The advantage of using a transparent cage is that the experimenter can observe the mouse from outside the cage without touching the cage. However, mice may recognise the environment outside the cage and change their behaviour. We speculated that mice housed in transparent cages might recognise mice in neighbouring cages. We used only male mice in this experiment. C57BL/6 mice were kept in transparent rearing cages with open lids, and the cage positions were maintained for 3 weeks. Subsequently, we examined how mice behaved toward cagemate mice, mice from neighbouring cages, and mice from distant cages. We compared the level of interest in mice using a social preference test. Similar to previous reports, subject mice showed a high degree of interest in unfamiliar mice from distant cages. By contrast, subject mice reacted to mice from neighbouring cages as familiar mice, similar to cagemate mice. This suggests that mice housed in transparent cages with open lids perceive the external environment and identify mice in neighbouring cages. Researchers should pay attention to the environment outside the mouse cage, especially for the social preference test.

Neurophysiological and behavioral synchronization in group-living and sleeping mice

Social interactions profoundly influence animal development, physiology, and behavior. Yet, how sleep-a central behavioral and neurophysiological process-is modulated by social interactions is poorly understood. Here, we characterized sleep behavior and neurophysiology in freely moving and co-living mice under different social conditions. We utilized wireless neurophysiological devices to simultaneously record multiple individuals within a group for 24 h, alongside video acquisition. We first demonstrated that mice seek physical contact before sleep initiation and sleep while in close proximity to each other (hereafter, "huddling"). To determine whether huddling during sleep is a motivated behavior, we devised a novel behavioral apparatus allowing mice to choose whether to sleep in close proximity to a conspecific or in solitude, under different environmental conditions. We also applied a deep-learning-based approach to classify huddling behavior. We demonstrate that mice are willing to forgo their preferred sleep location, even under thermoneutral conditions, to gain access to social contact during sleep. This strongly suggests that the motivation for prolonged physical contact-which we term somatolonging-drives huddling behavior. We then characterized sleep architecture under different social conditions and uncovered a social-dependent modulation of sleep. We also revealed coordination in multiple neurophysiological features among co-sleeping individuals, including in the timing of falling asleep and waking up and non-rapid eye movement sleep (NREMS) intensity. Notably, the timing of rapid eye movement sleep (REMS) was synchronized among co-sleeping male siblings but not co-sleeping female or unfamiliar mice. Our findings provide novel insights into the motivation for physical contact and the extent of social-dependent plasticity in sleep.

Whole-cage randomization for animal studies with unequal cage or group sizes

ABSTRACT Following good statistical practice, in vivo study investigators allocate animals into two or more treatment groups using a randomization routine to eliminate selection bias and balance known and unknown confounding factors. For some studies, however, randomization at the individual animal level cannot be implemented. For example, for studies that involve co-housed male mice, an animal-level randomization can place unfamiliar mice together in the same cage, which can trigger fighting. To meet the ethical obligations to enhance the welfare of an animal used in science, the experimental procedures are, therefore, often modified, and male mice, possibly from the same brood, may be housed together. It follows that animal allocation into groups must proceed at the whole-cage level. Given the small sample sizes in animal studies, controlling baseline variables can be quite challenging. The difficulty greatly increases with a whole-cage randomization restriction. When the number of animals per cage or the treatment group sizes are unequal, there is no algorithm in the literature to perform the task. We propose a novel, fast, and reliable algorithm to provide a whole-cage randomization that balances one or more baseline variables across groups. The algorithm was applied to a realistic example dataset.

An Insula-Enriched Regulator of Retinoic Acid Marks a New Intersection in the Neural Circuitry of Mouse Social Behavior

An Insula-Enriched Regulator of Retinoic Acid Marks a New Intersection in the Neural Circuitry of Mouse Social Behavior

A Standardized Protocol for Early-life Stress-induced Social Defeat in Mice.

Neuropsychiatric diseases, like depression, have a considerable and persistent impact on human health; however, little is known about their underlying pathogenesis. Social defeat is a model for stress-induced psychopathologies that could present with behaviors resembling those observed in humans with depression. However, previous animal models of social defeat mainly focus on adults. Here, we re-design the protocol of early-life stress-induced social defeat paradigm, which is based on a classic resident-intruder model. Briefly, each two-week-old experimental mouse of C57BL/6 strain is introduced into the home cage of an unfamiliar CD1 aggressor mouse for 30 min per day for 10 consecutive days. Later, all experimental mice are raised individually for another month. Finally, the mice are identified as defeated through social interaction and open field tests. This model has been shown to be etiological and predictive and provide high validity and could be a powerful tool to investigate the underlying pathogenesis of early onset depression. Graphical overview.

Locus Coeruleus-Noradrenergic Neurons Regulate Stress Coping During Subchronic Exposure to Social Threats: A Characteristic Feature in Postpartum Female Mice.

Stress-coping strategies have been implicated in depression. The control of stress coping may improve the symptom and higher prevalence of depression during the postpartum period in women. However, the neuronal mechanisms underlying stress coping remain to be fully elucidated in postpartum women. In this study, we examined how locus coeruleus-noradrenergic (LC-NA) neurons, which have been associated with both stress coping and depression, regulate changes in coping style induced by subchronic exposure to unfamiliar male mice as a social threat in postpartum female mice. In contrast to virgin females, dams exposed to unfamiliar males daily for four consecutive days showed reduced immobility duration in the forced swim test, indicating that exposure to unfamiliar males decreased passive stress coping in dams. Exposure to unfamiliar males also decreased sucrose palatability in the sucrose preference test and suppressed the crouching behavior in the maternal care test but did not affect anxiety-like behavior in the hole-board test in dams. In fiber photometry analyses, LC-NA neurons showed differential activity between dams and virgin females in response to unfamiliar males. Chemogenetic inhibition of LC-NA neurons during exposure to unfamiliar males prevented the social threat-induced decrease in immobility duration in the forced swim test in dams. Furthermore, inhibition or activation of LC-NA neurons exacerbated crouching behavior in dams. These results indicate that LC-NA neurons regulate the social threat-induced decrease in passive stress coping and relieve social threat-induced inhibition of maternal care in postpartum female mice.

The mu opioid receptor and the orphan receptor GPR151 contribute to social reward in the habenula

The mu opioid receptor (MOR) and the orphan GPR151 receptor are inhibitory G protein coupled receptors that are enriched in the habenula, a small brain region involved in aversion processing, addiction and mood disorders. While MOR expression in the brain is widespread, GPR151 expression is restricted to the habenula. In a previous report, we created conditional ChrnB4-Cre × Oprm1fl/fl (so-called B4MOR) mice, where MORs are deleted specifically in Chrnb4-positive neurons restricted to the habenula, and shown a role for these receptors in naloxone aversion. Here we characterized the implication of habenular MORs in social behaviors. B4MOR−/− mice and B4MOR+/+ mice were compared in several social behavior measures, including the chronic social stress defeat (CSDS) paradigm, the social preference (SP) test and social conditioned place preference (sCPP). In the CSDS, B4MOR−/− mice showed lower preference for the social target (unfamiliar mouse of a different strain) at baseline, providing a first indication of deficient social interactions in mice lacking habenular MORs. In the SP test, B4MOR−/− mice further showed reduced sociability for an unfamiliar conspecific mouse. In the sCPP, B4MOR−/− mice also showed impaired place preference for their previous familiar littermates after social isolation. We next created and tested Gpr151−/− mice in the SP test, and also found reduced social preference compared to Gpr151+/+ mice. Altogether our results support the underexplored notion that the habenula regulates social behaviors. Also, our data suggest that the inhibitory habenular MOR and GPR151 receptors normally promote social reward, possibly by dampening the aversive habenula activity.

A circuit from dorsal hippocampal CA3 to parvafox nucleus mediates chronic social defeat stress-induced deficits in preference for social novelty.

The preference for social novelty is crucial to the social life of humans and rodents. However, the neural mechanisms underlying social novelty preference are poorly understood. Here, we found that chronic social defeat stress (CSDS) reduced the preference for social novelty in mice by impairing the response of CaMKIIα+ neurons in the CA3 region of dorsal hippocampus (dCA3) during approach to an unfamiliar mouse. The deficits of social novelty preference in CSDS-treated mice were reversed by activating the output from dCA3 to the GABAergic neurons in the lateral septum (LS). The activation of GABAergic projection from LS recruited a circuit that inhibited the Foxb1+ neurons in the parvafox nucleus (PFN), which drove social avoidance by projecting to the lateral periaqueductal gray (lPAG). These results suggest that a previously unidentified circuit of dCA3CaMKIIα+→LSGABA+→PFNFoxb1+→lPAG mediates the deficits of social novelty preference induced by CSDS.

Preventive effect of a Kampo medicine, kososan, on recurrent depression in a mouse model of repeated social defeat stress.

Depression is deemed a mood disorder characterized by a high rate of relapse. Therefore, overcoming of the recurrent depression is globally expecting. Kososan, a traditional Japanese herbal medicine, has been clinically used for mild depressive mood, and our previous studies have shown some evidence for its antidepressive-like efficacy in experimental animal models of depression. However, it remains unclear whether kososan has beneficial effects on recurrent depression. Here, we examined its effect using a mouse model of modified repeated social defeat stress (SDS) paradigm. Male BALB/c mice were exposed to a 5-min SDS from unfamiliar aggressive CD-1 mice for 5days. Kososan extract (1.0kg/kg/day) or an antidepressant milnacipran (60mg/kg/day) was administered orally for 26days (days 7-32) to depression-like mice with social avoidant behaviors on day 6. Single 5min of SDS was subjected to mice recovered from the social avoidance on day 31, and then the recurrence of depression-like behaviors was evaluated on day 32. Hippocampal gene expression patterns were also assayed by DNA microarray analysis. Water- or milnacipran-administered mice resulted in a recurrence of depression-like behaviors by re-exposure of single SDS, whereas kososan-administered mice did not recur depression-like behaviors. Distinct gene expression patterns were also found for treating kososan and milnacipran. Collectively, this finding suggests that kososan exerts a preventive effect on recurrent depression-like behaviors in mice. Pretreatment of kososan is more useful for recurrent depression than that of milnacipran.

Phenanthrene induces autism-like behavior by promoting oxidative stress and mTOR pathway activation

Autism is thought to be associated with both environmental and genetic factors. Phenanthrene (Phe) makes up a relatively high proportion of the low-ring polycyclic aromatic hydrocarbons. However, the association between exposure to Phe and Autism remain unclear. In this study, the effect and mechanisms of phenanthrene exposure on autistic behavior were investigated. Three-week-old male Kunming mice were exposed to doses of 5, 50, or 500 μg/kg/d Phe for 22 days. Exposure to phenanthrene induced a marked decrease in the activity of the mice in the central area in the open field test, and caused a significant decrease in communication with unfamiliar mice in the three-chambered social test. The hippocampus of the mice exposed to high concentrations of Phe showed pathological changes. Exposure to phenanthrene induced an increase in the levels of ROS and a decrease in levels of glutathione, and caused a significant decrease in the expression of Shank3 and Beclin1. This also led to an increase in the phosphorylation levels of Akt and mTOR. However, administering Rapamycin or vitamin E, inhibited the oxidative stress and activation of the mTOR pathway induced by Phe exposure, effectively alleviating the above-mentioned autistic-like anxious social behaviors. These results indicate that exposure to phenanthrene will lead to autism-like behavior. The underlying mechanism involves oxidative stress and the mTOR pathway.

Emotional Impairments and Neuroinflammation are Induced in Male Mice Invulnerable to Repeated Social Defeat Stress

Prolonged stress triggers neuroinflammation, which plays a significant role in the development of depression; however, stressed people do not always suffer from depression because of individual differences in stress vulnerability. Negative cognitive bias (NCB) toward pessimistic judgment often underlies depressive episodes. However, a relationship between stress vulnerability, neuroinflammation, and NCB remains elusive. In addition, an animal model with all the traits would be a powerful tool for studying the etiology of depression and its therapeutic approaches. Accordingly, this study evaluated the effect of stress vulnerability on neuroinflammation and depression-related behaviors, including NCB in males, using a modified version of repeated social defeat stress (mRSDS) paradigm, a validated animal model of psychosocial stress. Exposure to mRSDS, consisting of 5 min of social defeat by unfamiliar CD-1 aggressor mice for five consecutive days, caused NCB, which co-occurred with depressive- and anxiety-like behaviors, and neuroinflammation in male BALB/c mice. Treatment with minocycline, an antibiotic with anti-inflammatory property, blocked mRSDS-induced depressive-like behaviors and neuroinflammation, but not NCB, indicating the limited effect of an anti-inflammatory intervention. In addition, marked differences were found in neuroinflammatory profiles and hippocampal gene expression patterns between resilient and unstressed mice, as well as between susceptible and resilient mice. Therefore, mice resilient to mRSDS are indeed not intact. Our findings provide insights into the unique features of the mRSDS model in male BALB/c mice, which could be used to investigate the etiological mechanisms underlying depression as well as bridge the gap in the relationship between stress vulnerability, neuroinflammation, and NCB in males.

Differential sensitivity to detect prosocial effects of 3,4-methylenedioxymethamphetamine (MDMA) in different social approach paradigms in mice.

A recreational drug, 3,4‐methylenedioxymethamphetamine (MDMA), has prosocial effects including increased sociability, enhancement of trust feelings, and empathy. Although several methods, such as the social interaction and three chamber tests, have been used, the neural mechanisms underlying the prosocial effects have not been well understood. In the present study, based on a social approach paradigm using a single‐chamber apparatus, we have developed two reproducible and simple social approach tests, SAT1 and SAT2, in ICR mice. In the SAT1, an unfamiliar mouse was set in a wire mesh cylinder cage that was placed in the center of a rectangular open field, while in the SAT2, an unfamiliar mouse was set in a wire mesh rectangular cage that was placed along a wall of a rectangular open field. Although MDMA treatment enhanced sociability in both SAT1 and SAT2, the ratio of high sociability mice was higher in the SAT2 than in the SAT1, indicating a differential sensitivity to detect the prosocial effects. Thus, we suggest that the SAT2 is a promising and suitable method to explore the neuronal mechanisms underlying the effects of MDMA.

Different effects of chronic social defeat on social behavior and the brain CRF system in adult male C57 mice with different susceptibilities

Chronic social defeat stress (CSDS) has been found to produce different impacts on anxiety-like behaviors, spatial cognitive function and memory in rodents with different susceptibilities. However, the impacts of chronic social defeat on social behaviors in adult male mice with different susceptibilities to social defeat and the underlying mechanisms in the brain remain unclear. In the present study, we found that ten days of social defeat reduced the tendency of susceptible adult male C57 mice to approach an unfamiliar individual and increased their avoidance of an unfamiliar CD-1 mouse but had no effects on resilient individuals. In addition, CSDS enhanced anxiety-like behavior in susceptible animals, but produced no effects in the resilient group. Meanwhile, CSDS increased the number of corticotropin-releasing factor (CRF)-positive neurons in the paraventricular nucleus of the hypothalamus and CRF-R2-positive neurons in the accumbens nucleus shell in both resilient and susceptible animals. CSDS increased the number of CRF-R1-positive neurons and CRF-R1 mRNA expression in the prelimbic cortex (PrL) and the number of CRF-R2-positive neurons in the basolateral amygdala, but reduced the number of CRF-R2-positive neurons and mRNA expression in the PrL in susceptible animals. Therefore, the different effects of CSDS on sociability and anxiety-like behavior in mice with different susceptibilities may be associated with region- and type-specific alterations in CRF receptor levels. These findings help us understand the underlying mechanism by which social stress affects emotion and social behavior and provides an important basis for the treatment of disorders of social and emotional behavior caused by social stress.

G\u03b1i2+ vomeronasal neurons govern the initial outcome of an acute social competition

Pheromone detection by the vomeronasal organ (VNO) mediates important social behaviors across different species, including aggression and sexual behavior. However, the relationship between vomeronasal function and social hierarchy has not been analyzed reliably. We evaluated the role of pheromone detection by receptors expressed in the apical layer of the VNO such as vomeronasal type 1 receptors (V1R) in dominance behavior by using a conditional knockout mouse for G protein subunit Gαi2, which is essential for V1R signaling. We used the tube test as a model to analyze the within-a-cage hierarchy in male mice, but also as a paradigm of novel territorial competition in animals from different cages. In absence of prior social experience, Gαi2 deletion promotes winning a novel social competition with an unfamiliar control mouse but had no effect on an established hierarchy in cages with mixed genotypes, both Gαi2−/− and controls. To further dissect social behavior of Gαi2−/− mice, we performed a 3-chamber sociability assay and found that mutants had a slightly altered social investigation. Finally, gene expression analysis in the medial prefrontal cortex (mPFC) for a subset of genes previously linked to social status revealed no differences between group-housed Gαi2−/− and controls. Our results reveal a direct influence of pheromone detection on territorial dominance, indicating that olfactory communication involving apical VNO receptors like V1R is important for the outcome of an initial social competition between two unfamiliar male mice, whereas final social status acquired within a cage remains unaffected. These results support the idea that previous social context is relevant for the development of social hierarchy of a group. Overall, our data identify two context-dependent forms of dominance, acute and chronic, and that pheromone signaling through V1R receptors is involved in the first stages of a social competition but in the long term is not predictive for high social ranks on a hierarchy.

The presence of a social stimulus reduces cocaine-seeking in a place preference conditioning paradigm.

One challenge in the treatment of substance use disorders is to re-engage the interest toward non-drug-related activities. Among these activities, social interaction has had a prominent role due to its positive influence on treatment outcome. Our aim was to study whether the presence of a social stimulus during the cocaine-induced conditioned place preference test was able to reduce the time spent in the drug-paired compartment. For that purpose, mice were trained for four days on a conditioned place preference task with one compartment paired with cocaine and the opposite with saline. On the test day, we introduced an unfamiliar juvenile male mouse into the saline-conditioned compartment (inside a pencil cup) to analyse the animal preference towards the two rewarding stimuli (cocaine vs mouse). Additionally, to discard the possible effect of novelty, as well as the housing condition (social isolation) on social preference, we decided to include a novel object during the test session, as well as perform the same conditioned place preference protocol with a group of animals in social housing conditions. The social stimulus was able to reduce the preference for cocaine and enhance the active interaction with the juvenile mouse (sniffing) compared to the empty pencil cup paired with the drug. The introduction of a novel object during the test session did not reduce the preference for the cocaine-paired compartment, and interestingly, the preference for the social stimulus was independent of the housing condition. c-Fos immunohistochemistry revealed a different pattern of activation based on cocaine-paired conditioning or the presence of social stimulus. These results suggest that social interaction could constitute a valuable component in the treatment of substance use disorders by reducing the salience of the drug.

Influence of Sex on Cognition and Peripheral Neurovascular Function in Diabetic Mice.

Cognition impairment and peripheral neuropathy (DPN) are two major complications of diabetes. The aim of the present study is to investigate the effect of sex differences on cognition and DPN in diabetic mice. Male and female BKS.Cg-m+/+Leprdb/J (db/db) and db/m mice were used. At ages of 20 and 30 weeks, all animals were subjected to learning, memory and neurological function tests. Regional blood flow in footpad and sciatic nerves were measured using laser Doppler flowmetry. Our data showed that male db/db mice aged 20 weeks and 30 weeks spent significantly more time to locate the hidden platform in the correct quadrant and spent significantly less time exploring the cage with a new stranger mouse compared to aged-matched female db/db mice. Electrophysiological recordings showed that male db mice aged 30 weeks had significantly reduced motor and sensory nerve conduction velocity compared with females. Hot plate and tactile allodynia tests revealed that males exhibited significantly higher thermal and mechanical latency than females. Male db mice aged 30 weeks displayed significantly reduced blood perfusion in sciatic nerve and footpad tissues compared with females. In addition, compared with male and female non-diabetic db/m mice, db/db mice exhibited increased time spent on locating the hidden platform, decreased time spent on exploring the novel odor bead and an unfamiliar mouse, as well as showed significantly lower levels of blood flow, lower velocity of MCV and SCV, higher thermal and mechanical latencies. Blood glucose levels and body weight were not significantly different between male and female diabetic animals (age 30 weeks), but male db mice showed a higher serum total cholesterol content. Together, our data suggest that males develop a greater extent of diabetes-induced cognition deficits and peripheral neurovascular dysfunction than females.

Transmission of food preference between unfamiliar house mice (Mus musculus domesticus) is dependent on social context.

Rodents obtain information about a new food source through olfactory cues of conspecifics and consequently develop an attraction for this diet. Generally, physical contact between an observer and a demonstrator that has recently consumed a novel food item is required to allow the social transmission of food preference (STFP). However, in natural populations of house mice, social encounters between unfamiliar individuals usually turn into a fight. Thus, social intolerance between the individuals involved could prevent STFP. It has been shown that the feces of rodents can act as a social stimulus and promote STFP in mice, which could reduce the social constraints associated with an encounter. Here, we examined the acquisition of the STFP in female house mice of wild origin (Mus musculus domesticus) after a direct encounter with a familiar and unfamiliar female, and after the presentation of olfactory marks of an unfamiliar female. Unlike in encounters between familiar females, our results did not provide significant support for the existence of STFP after encounters between two unfamiliar females, independently of the occurrence or absence of offensive agonistic behavior. However, STFP through olfactory marks of an unfamiliar female was effective. We suggest that the social context might strongly impair direct STFP, not necessarily via the unfamiliarity of the information provider but rather via its physical presence. (PsycINFO Database Record