Group-housed Male Mice Research Articles

Partially divided caging reduces overall aggression and anxiety which may indicate improved welfare in group housed male C57BL/6J mice

Deciding which environmental enrichment is used in mouse caging is often subjective, with cost frequently prevailing over welfare benefits, including aggression and anxiety. While many devices introduced to encourage natural behaviors and reduce aggression show mixed results, we have previously demonstrated significant reductions in aggressive behavior between group-housed male mice housed in partially divided caging. To further assess behavior, we have raised male C57BL/6J mice in either partially divided caging or in standard caging with no divider. Animal behavior was tested on rotarod, open field, novel object recognition, elevated plus maze, and Y maze. Body weights were taken weekly beginning at weaning and bite wounds were counted weekly beginning at 133 days old. Aggressive behavior was recorded weekly beginning at 133 days old. Results indicated significantly less anxiety in the elevated-plus maze, statistically fewer bite wounds, and a statistically significant decrease in aggressive behaviors of mice in partially divided caging compared to mice in standard cages. We conclude that reductions in anxiety, aggressive behavior, and bite wounds may indicate improved overall welfare for non-sibling, group housed male mice.

The impact of cage dividers on mouse aggression, dominance and hormone levels.

Home cage aggression in group-housed male mice is a major welfare concern and may compromise animal research. Conventional cages prevent flight or retreat from sight, increasing the risk that agonistic encounters will result in injury. Moreover, depending on social rank, mice vary in their phenotype, and these effects seem highly variable and dependent on the social context. Interventions that reduce aggression, therefore, may reduce not only injuries and stress, but also variability between cage mates. Here we housed male mice (Balb/c and SWISS, group sizes of three and five) with or without partial cage dividers for two months. Mice were inspected for wounding weekly and home cages were recorded during housing and after 6h isolation housing, to assess aggression and assign individual social ranks. Fecal boli and fur were collected to quantify steroid levels. We found no evidence that the provision of cage dividers improves the welfare of group housed male mice; The prevalence of injuries and steroid levels was similar between the two housing conditions and aggression was reduced only in Balb/c strain. However, mice housed with cage dividers developed less despotic hierarchies and had more stable social ranks. We also found a relationship between hormone levels and social rank depending on housing type. Therefore, addition of cage dividers may play a role in stabilizing social ranks and modulating the activation of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes, thus reducing phenotypic variability between mice of different ranks.

Exogenous oxytocin microinjection into the nucleus accumbens shell attenuates social dominance in group-housed male mice

The nucleus accumbens (NAc), a part of the brain's limbic system, is involved in a variety of brain functions, including reward motivation and social hierarchy. Here, the study investigated the effect of intra-NAc different subregions microinjections of oxytocin on social hierarchy regulation. The hierarchical ranking of group-housed male mice in laboratory settings was determined through the tube test, and a new reliable and robust behavior assay—the mate competition test—was proposed. The mice were randomly divided into two groups, and the bilateral guide cannula was implanted into the shell and core of the NAc, respectively. After social dominance stabilized, changes in social hierarchy were determined through the tube test, warm spot, and mate competition tests. Intra-NAc shell microinjections of oxytocin (0.5 μg/site), but not the core (0.5 μg/site), significantly reduced the social dominance of mice. In addition, oxytocin microinjection into both the shell and core of the NAc significantly increased locomotor ability without affecting anxious behaviors. These findings are tremendously important in understanding the functions of the NAc subregions for social dominance and are more likely to indicate the potential of an oxytocin therapeutic strategy for psychiatric disorders and social impairments.

Aggression in Group-Housed Male Mice: A Systematic Review.

Aggression among group-housed male mice is a major animal welfare concern often observed at animal facilities. Studies designed to understand the causes of male mice aggression have used different methodological approaches and have been heterogeneous, using different strains, environmental enrichments, housing conditions, group formations and durations. By conducting a systematic literature review based on 198 observed conclusions from 90 articles, we showed that the methodological approach used to study aggression was relevant for the outcome and suggested that home cage observations were better when studying home cage aggression than tests provoking aggression outside the home cage. The study further revealed that aggression is a complex problem; one solution will not be appropriate for all animal facilities and all research projects. Recommendations were provided on promising tools to minimize aggression, based on the results, which included what type of environmental enrichments could be appropriate and which strains of male mice were less likely to be aggressive.

Effect of environmental enrichment on aggression and the expression of brain-derived neurotrophic factor transcript variants in group-housed male mice

Social and environmental factors influence behavior via modulation of brain physiological functions. Environmental enrichment (EE) is an animal housing technique that provides complex sensory, motor, and social stimulation, leading to modifications in the innate aggressiveness in group-housed laboratory mice. Brain-derived neurotrophic factor (BDNF) is encoded by multiple splice variants and plays a critical role in controlling aggressive behavior in a transcript variant-specific manner. BDNF mediates the beneficial effects of EE on a variety of pathophysiological conditions. These findings led to the hypothesis that EE reduces aggressive behavior by altering the expression of Bdnf mRNA in a transcript variant-specific manner. To test this hypothesis, 3–4-week-old male C57BL/6 mice were randomly group-housed (5 mice per cage) under standard or EE conditions for 6–8 weeks. Aggressive behavior was monitored and levels of Bdnf mRNA variants in aggression-related brain regions were measured. Mice housed in EE cages displayed a significantly lower frequency of aggressive interactions compared to control mice. EE increased levels of Bdnf mRNA variant I (Bdnf I) in the amygdala while it reduced levels of Bdnf I in the hypothalamus, hippocampus, prefrontal cortex, parietal cortex, and brainstem. Meanwhile, EE did not significantly alter levels of Bdnf mRNA variants IIc, IV, and VI in all brain regions examined. These findings support the hypothesis that EE diminishes inter-male aggression by altering Bdnf mRNA expression in a transcript variant-specific and brain region-specific manner. Specifically, brain region-specific alterations in Bdnf I expression may partly mediate EE-induced suppression of inter-male aggression.

The epidemiology of fighting in group-housed laboratory mice

Injurious home-cage aggression (fighting) in mice affects both animal welfare and scientific validity. It is arguably the most common potentially preventable morbidity in mouse facilities. Existing literature on mouse aggression almost exclusively examines territorial aggression induced by introducing a stimulus mouse into the home-cage of a singly housed mouse (i.e. the resident/intruder test). However, fighting occurring in mice living together in long-term groups under standard laboratory housing conditions has barely been studied. We performed a point-prevalence epidemiological survey of fighting at a research institution with an approximate 60,000 cage census. A subset of cages was sampled over the course of a year and factors potentially influencing home-cage fighting were recorded. Fighting was almost exclusively seen in group-housed male mice. Approximately 14% of group-housed male cages were observed with fighting animals in brief behavioral observations, but only 14% of those cages with fighting had skin injuries observable from cage-side. Thus simple cage-side checks may be missing the majority of fighting mice. Housing system (the combination of cage ventilation and bedding type), genetic background, time of year, cage location on the rack, and rack orientation in the room were significant risk factors predicting fighting. Of these predictors, only bedding type is easily manipulated to mitigate fighting. Cage ventilation and rack orientation often cannot be changed in modern vivaria, as they are baked in by cookie-cutter architectural approaches to facility design. This study emphasizes the need to invest in assessing the welfare costs of new housing and husbandry systems before implementing them.

The occurrence of tarsal injuries in male mice of C57BL/6N substrains in multiple international mouse facilities.

Dislocation in hindlimb tarsals are being observed at a low, but persistent frequency in group-housed adult male mice from C57BL/6N substrains. Clinical signs included a sudden onset of mild to severe unilateral or bilateral tarsal abduction, swelling, abnormal hindlimb morphology and lameness. Contraction of digits and gait abnormalities were noted in multiple cases. Radiographical and histological examination revealed caudal dislocation of the calcaneus and partial dislocation of the calcaneoquartal (calcaneus-tarsal bone IV) joint. The detection, frequency, and cause of this pathology in five large mouse production and phenotyping centres (MRC Harwell, UK; The Jackson Laboratory, USA; The Centre for Phenogenomics, Canada; German Mouse Clinic, Germany; Baylor College of Medicine, USA) are discussed.

Identity domains capture individual differences from across the behavioral repertoire.

Personality traits can offer considerable insight into the biological basis of individual differences. However, existing approaches toward understanding personality across species rely on subjective criteria and limited sets of behavioral readouts, which result in noisy and often inconsistent outcomes. Here we introduce a mathematical framework for describing individual differences along dimensions with maximum consistency and discriminative power. We validate this framework in mice, using data from a system for high-throughput longitudinal monitoring of group-housed male mice that yields a variety of readouts from across the behavioral repertoire of individual animals. We demonstrate a set of stable traits that capture variability in behavior and gene expression in the brain, allowing for better-informed mechanistic investigations into the biology of individual differences.

Consequences of housing conditions and interindividual diversity in rodent models of acquired epilepsy.

Consequences of housing conditions and interindividual diversity in rodent models of acquired epilepsy.

Partial cage division significantly reduces aggressive behavior in male laboratory mice.

Aggression in mice often results in injury leading to unplanned euthanasia or the initiation of protocols to isolate animals, thereby increasing research costs and straining resources. Here, we tested if adding a partial cage divider into existing mouse cages affected aggressive-like behavior in group-housed male mice (18 mice; 3 per cage). Mice were randomly assigned to one of two groups upon arrival to the vivarium: (1) standard cage; (2) cage with a partial cage divider. Behavioral observation over 12 hours were conducted at day one, two, and seven after receipt at the facility in order to assess aggression during the course of establishing dominance hierarchies. Observers blinded to study design and hypothesis scored each video for the number and type of aggressive behaviors, which were summed for each hour and analyzed. Results indicated a statistically significant decrease in aggressive behaviors of mice in cages with dividers compared to mice in standard cages. We conclude that cage dividers, which resemble burrows and provide access to common food/water, may promote rigorous research by reducing the number of animals used in a study and refining housing, thus, improving animal welfare.

Hierarchy in the home cage affects behaviour and gene expression in group-housed C57BL/6 male mice

Group-housed male mice exhibit aggressive behaviour towards their cage mates and form a social hierarchy. Here, we describe how social hierarchy in standard group-housed conditions affects behaviour and gene expression in male mice. Four male C57BL/6 mice were kept in each cage used in the study, and the social hierarchy was determined from observation of video recordings of aggressive behaviour. After formation of a social hierarchy, the behaviour and hippocampal gene expression were analysed in the mice. Higher anxiety- and depression-like behaviours and elevated gene expression of hypothalamic corticotropin-releasing hormone and hippocampal serotonin receptor subtypes were observed in subordinate mice compared with those of dominant mice. These differences were alleviated by orally administering fluoxetine, which is an antidepressant of the selective serotonin reuptake inhibitor class. We concluded that hierarchy in the home cage affects behaviour and gene expression in male mice, resulting in anxiety- and depression-like behaviours being regulated differently in dominant and subordinate mice.

Combined Effects of Acamprosate and Escitalopram on Ethanol Consumption in Mice.

Major depression is one of the most prevalent psychiatry comorbidities of alcohol use disorders (AUD). As negative emotions can trigger craving and increase the risk of relapse, treatments that target both conditions simultaneously may augment treatment success. Previous studies showed a potential synergistic effect of Food and Drug Administration approved medication for AUD acamprosate and the antidepressant escitalopram. In this study, we investigated the effects of combining acamprosate and escitalopram on ethanol (EtOH) consumption in stress-induced depressed mice. Forty singly housed C57BL/6J male mice were subjected to chronic unpredictable stress. In parallel, 40 group-housed male mice were subjected to normal husbandry. After 3weeks, depressive- and anxiety-like behaviors and EtOH consumption were assessed. For the next 7days, mice were injected with saline, acamprosate (200mg/kg; twice/d), escitalopram (5mg/kg; twice/d), or their combination (n=9 to 11/drug group/stress group). Two-bottle choice limited-access drinking of 15% EtOH and tap water was performed 3hours into dark phase immediately after the daily dark phase injection. EtOH drinking was monitored for another 7days without drug administration. Mice subjected to the chronic unpredictable stress paradigm for 3weeks showed apparent depression- and anxiety-like behaviors compared to their nonstressed counterparts including longer immobility time in the forced swim test and lower sucrose preference. Stressed mice also displayed higher EtOH consumption and preference in a 2-bottle choice drinking test. During the drug administration period, the escitalopram-only and combined drug groups showed significant reduction in EtOH consumption in nonstressed mice, while only the combined drug group showed significantly reduced consumption in stressed mice. However, such reduction did not persist into the postdrug administration period. The combination of acamprosate and escitalopram suppressed EtOH intake in both nonstressed and stressed mice; hence, this combination is potentially helpful for AUD individuals with or without comorbid depression to reduce alcohol use.

A Social Network Approach Reveals Associations between Mouse Social Dominance and Brain Gene Expression.

Modelling complex social behavior in the laboratory is challenging and requires analyses of dyadic interactions occurring over time in a physically and socially complex environment. In the current study, we approached the analyses of complex social interactions in group-housed male CD1 mice living in a large vivarium. Intensive observations of social interactions during a 3-week period indicated that male mice form a highly linear and steep dominance hierarchy that is maintained by fighting and chasing behaviors. Individual animals were classified as dominant, sub-dominant or subordinate according to their David’s Scores and I& SI ranking. Using a novel dynamic temporal Glicko rating method, we ascertained that the dominance hierarchy was stable across time. Using social network analyses, we characterized the behavior of individuals within 66 unique relationships in the social group. We identified two individual network metrics, Kleinberg’s Hub Centrality and Bonacich’s Power Centrality, as accurate predictors of individual dominance and power. Comparing across behaviors, we establish that agonistic, grooming and sniffing social networks possess their own distinctive characteristics in terms of density, average path length, reciprocity out-degree centralization and out-closeness centralization. Though grooming ties between individuals were largely independent of other social networks, sniffing relationships were highly predictive of the directionality of agonistic relationships. Individual variation in dominance status was associated with brain gene expression, with more dominant individuals having higher levels of corticotropin releasing factor mRNA in the medial and central nuclei of the amygdala and the medial preoptic area of the hypothalamus, as well as higher levels of hippocampal glucocorticoid receptor and brain-derived neurotrophic factor mRNA. This study demonstrates the potential and significance of combining complex social housing and intensive behavioral characterization of group-living animals with the utilization of novel statistical methods to further our understanding of the neurobiological basis of social behavior at the individual, relationship and group levels.

Group housing of male CD1 mice: Reflections from toxicity studies

Owing to their naturally aggressive behaviour, male mice are often housed individually in toxicity studies. However, several publications advocate group-housing of mice to enable normal social behaviour and interactions between the animals. This refinement project aimed at facilitate group-housing in toxicity studies. A handling procedure, including key factors such as allocation into groups before sexual maturation, transfer of used nesting material into clean cages and avoidance of external changes, that makes group-housing of male CD-1 mice possible in long-term toxicity studies has been developed at Safety Assessment within AstraZeneca, Sweden. Observations on the effect on aggression/fighting in group-housed male mice following different procedures performed in toxicity studies have shown that temporary removal of animals from the group for blood or urine sampling does not affect the group dynamics. However, temporary removal of animals for mating leads to fighting if the animals are taken back to the original group. Treatment with test compound might affect the general condition of the animals and the social hierarchy could be changed. In such cases aggression/fighting might occur and the animals have to be separated. Our experience clearly indicates that group housing of male mice in long-term studies leads to more easily handled animals, as compared with individually housed mice.

Environmental enrichment influences brain cytokine variations elicited by social defeat in mice

Environmental enrichment may protect against some of the adverse behavioural and biological effects of stressors. However, unlike the effects seen in some species, among male mice housed in groups, enrichment may alter social stability, encourage competition and aggression, and thus promote the establishment of a stressful environment. A potent psychosocial stressor such as social defeat in mice promotes brain neurochemical changes as well as pro-inflammatory cytokine variations in the prefrontal cortex (PFC) and hippocampus. The present investigation demonstrated that enrichment in group-housed male mice, even in the relatively nonaggressive, although highly anxious BALB/cByJ strain encouraged the effects of a repeated social defeat stressor experienced 4 weeks later, especially with respect to corticosterone as well as hippocampal corticotropin-releasing hormone (CRH) and interleukin (IL)-6 variations. Moreover, within the hippocampus, enrichment itself was accompanied by modest reductions in the expression of the IL-1β receptor (IL-1r1). Thus, it seems that living in an enriched environment among group-housed male mice might promote a stressful environment that enhances basal hippocampal CRH and cytokine variations and increased vulnerability to further changes upon subsequent exposure to a social stressor.

Quantifying mouse social behavior

Event Abstract Back to Event Quantifying mouse social behavior S. E. Roian Egnor1*, Shay Ohayon2, Pietro Perona2 and Adam Taylor1 1 Howard Hughes Medical Institute - Janelia Farm Research Campus, United States 2 Caltech, United States Humans are social creatures, and deficits that impair social interaction can be much more disruptive to individual, family and society, than similarly severe sensory or motor deficits. This makes research into social deficits particularly urgent, but this urgency is hampered by the increased difficulty of modeling complex human social interactions with mouse behavior. Characterizing a social deficit requires first that you have a good idea of what a socially normal mouse looks like. This is partially complicated by the fact that one of the reasons that the mouse is so globally successful is that it is extremely plastic in the types of social behavior it can display. Mice can be successful at very low and very high population densities, deploying the same genetics to handle almost no social interactions or continual social interactions. Social relationships in mice develop over the course of many days, but standard tests of social competence are often brief, involving observation of two mice introduced into a cage for a short period. In addition, standard mouse husbandry allows only a fraction of the full mouse repertoire to be observed in the lab and the social and sexual isolation common in mouse husbandry practice can introduce repetitive/anxiety-related behaviors that may obscure natural behavior. To describe normal mouse social behavior in a quantitative way we have developed a video--based method to track the position and identity of group-housed male and female mice in a 60 cm x 60 cm enclosure over multiple days. Mice are bleach marked to allow unambiguous identification. Four ultrasonic microphones record vocalizations continuously during social interactions. Keywords: Mouse, tracking, trajectory, vocalization Conference: Tenth International Congress of Neuroethology, College Park. Maryland USA, United States, 5 Aug - 10 Aug, 2012. Presentation Type: Invited Symposium (only for people who have been invited to a particular symposium) Topic: Social Behavior Citation: Egnor S, Ohayon S, Perona P and Taylor A (2012). Quantifying mouse social behavior. Conference Abstract: Tenth International Congress of Neuroethology. doi: 10.3389/conf.fnbeh.2012.27.00051 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 02 May 2012; Published Online: 07 Jul 2012. * Correspondence: Dr. S. E. Roian Egnor, Howard Hughes Medical Institute - Janelia Farm Research Campus, Ashburn, United States, roian.egnor@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers S. E. Roian Egnor Shay Ohayon Pietro Perona Adam Taylor Google S. E. Roian Egnor Shay Ohayon Pietro Perona Adam Taylor Google Scholar S. E. Roian Egnor Shay Ohayon Pietro Perona Adam Taylor PubMed S. E. Roian Egnor Shay Ohayon Pietro Perona Adam Taylor Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

PRECLINICAL STUDY: Effects of bupropion, alone or coadministered with nicotine, on social behavior in mice

Bupropion, administered alone or combined with nicotine, is presently used to treat nicotine dependence. Despite experimental evidence of the complex behavioral actions of this drug, there have been little data reported about its effects on social behavior. Our main aim was to investigate the effects of acute administration of bupropion, alone or plus nicotine, on social interaction in mice. OF1 group-housed male mice were confronted in a neutral cage with an anosmic opponent during a 10 minutes encounter. Time allocated to body care and digging was reduced by administration of bupropion (40 mg/kg) both when administered alone and with nicotine (1 and 0.5 mg/kg). The lowest dose of bupropion (10 mg/kg) also reduced digging when combined with 1 mg/kg of nicotine. Time spent on non-social exploration and exploration from a distance was significantly higher in mice treated with bupropion (40 mg/kg) alone or combined with nicotine (1 and 0.5 mg/kg). The lowest dose of bupropion (10 mg/kg) increased non-social exploration when combined with 0.5 mg/kg of nicotine and exploration from a distance when combined with 1 mg/kg of nicotine. Ethopharmacological assessment of the behavior of groups of mice treated with different combinations of the two drugs indicates that nicotine can potentiate some of the behavioral effects of low doses of bupropion. Results also indicate that bupropion, either alone or combined with nicotine, has no significant effects on social investigation, suggesting that this drug does not induce a clear anxiolytic profile in OF1 mice.

Effects of a running wheel-igloo enrichment on aggression, hierarchy linearity, and stereotypy in group-housed male CD-1 (ICR) mice

Environmental enrichment is an important strategy to improve the welfare of laboratory animals. Running wheels might serve as enrichment devices for laboratory mice, since mice use them extensively when they are provided. However, competition among group-housed mice for such highly preferred enrichment devices could also lead to injurious aggression. We therefore assessed the effects of providing a running wheel-igloo enrichment on the social behaviour of group-housed male mice. CD-1 (ICR) mice ( n = 60, 20 per treatment) were housed in standard polycarbonate cages (five mice per cage) for 2 weeks (BASE), and then placed in either: (1) a standard cage with bedding (CONTROL), or (2) same as CONTROL, but with the addition of a Bio-Serv ® mouse running wheel-igloo (WHEEL) or (3) same as WHEEL, but with the running wheel glued in place so that it could not rotate (FIXED). Social behaviour and dominance ranks were assessed at the end of BASE and 2 weeks after imposition of treatments. There was increased escalated aggression in both enriched cages (FIXED, Tukey: T 8 = −8.31; P = 0.0003; WHEEL, Tukey: T 8 = −4.577; P = 0.0153), and decreased stereotypy in WHEEL (Tukey: T 8 = 4.226; P = 0.0237). There was also a decrease in dominance hierarchy linearity in enriched treatments (FIXED, Tukey: T 9 = 3.653; P = 0.0433; WHEEL, Tukey: T 9 = 6.273; P = 0.0014) and a negative correlation between hierarchy linearity and escalated aggression overall (GLM: F 1,7 = 61.41; P < 0.001; partial r = 0.90). Thus, providing the running wheel-igloo enrichment had a negative effect in that it increased potentially injurious aggression. Additionally, the decrease in hierarchy linearity suggests that the social structure in enriched groups was disrupted. The cause of the decrease in cage stereotypies in WHEEL is unknown, but could be because these stereotypies were re-directed towards stereotypic wheel-running, or because wheel-running reduced frustration due to limited opportunities for exploratory locomotion or caused a shift in the behavioural time budget. Despite this decrease in stereotypy, this form of enrichment is not beneficial for group-housed male CD-1 mice due to the associated increased aggression. However, female mice or males of less aggressive mouse strains might respond differently, and singly housed mice should generally benefit from such enrichment.

Changes in brain testosterone and allopregnanolone biosynthesis elicit aggressive behavior.

In addition to an action on metabolism, anabolic/androgenic steroids also increase sex drive and mental acuity. If abused, such steroids can cause irritability, impulsive aggression, and signs of major depression [Pearson, H. (2004) Nature 431, 500-501], but the mechanisms that produce these symptoms are unknown. The present study investigates behavioral and neurochemical alterations occurring in association with protracted (3-week) administration of testosterone propionate (TP) to socially isolated (SI) and group-housed male and female mice. Male but not female SI mice exhibit aggression that correlates with the down-regulation of brain neurosteroid biosynthesis. However, in female mice, long-term TP administration induces aggression associated with a decrease of brain allopregnanolone (Allo) content and a decrease (approximately 40%) of 5alpha-reductase type I mRNA expression. In spayed mice treated with TP, restitution experiments with progesterone and estrogen normalize brain Allo content and prevent aggression. Submicromolar doses of S-norfluoxetine (S-NFLX) that are insufficient to inhibit serotonin reuptake selectively increase brain Allo content and abolish TP-induced aggression. Our results support the view that TP-induced aggressive behavior is the result of a TP-mediated neurosteroid biosynthesis down-regulation that can be reversed by the S-NFLX-induced increase of brain Allo content.

Long-term effects of husbandry procedures on stress-related parameters in male mice of two strains.

In socially unstable groups of male laboratory mice, individuals may experience a chronic stress situation. Previous experiments have shown that the transfer of specific olfactory cues during cage cleaning, and the provision of nesting material decrease aggression and stress in group-housed male mice. In this study, the combined effect of these husbandry procedures were tested for their long-term effect on stress in groups of moderately aggressive (BALB/c) and severely aggressive (CD-1) male mice. The physiological and behavioural stress-related parameters used were body weight, food and water intake, spleen and thymus weight, adrenal tyrosine hydroxylase activity, urine corticosterone levels and behaviour in a cage emergence test. Long-term provision of nesting material and its transfer during cage cleaning was found to influence several stress-related physiological parameters. Mice housed in cages enriched with nesting material had lower urine corticosterone levels and heavier thymuses, and they consumed less food and water than standard-housed mice. Furthermore, marked differences were found between strains. CD-1 mice were less anxious in the cage emergence test, weighed more, ate and drank more, and had heavier thymuses but lighter spleens and lower corticosterone levels than BALB/c mice. We conclude that the long-term provision of nesting material, including the transfer of nesting material during cage cleaning, reduces stress and thereby enhances the welfare of laboratory mice.