Fluoroimidazoles as antiviral agents and inhibitors of polynucleotide biosynthesis.

Some recent studies relating the effects of individual housing (isolation) and group housing to behavior, physiology and neurochemistry in laboratory rats and mice are reviewed and these accounts related to comparable information derived from experiments employing “social stresses” e.g. subjecting the animal to defeat. The data is discussed in relation to the problem of whether individual housing constitutes a “stress” (in terms of adrenocortical and adrenal medullary functioning) in these species, as it appears to do in primates. In spite of the large number of papers which ascribe the behavioral and endocrine changes obtained in isolation versus grouping comparisons to the effects of “the isolation-induced stress syndrome”, it is concluded that, in terms of adrenal function, there is little evidence that isolation $\text{per}$$\text{se}$ constitutes a stress in rats and mice, although there is some evidence that adrenocortical reactivity is increased by housing animals in this manner. It should be noted that the wild progenitor of the laboratory strains of house mouse often appears to evidence territoriality. The view is advanced that the isolated condition in male mice may result in changes characteristic of territorial dominance. This may represent a mechanism for inducing social or territorial stability in this species. It appears that experiments involving physical isolation in laboratory rodents are unlikely to provide good models for the effects of “social deprivation” in man. It is thought that more studies employing measurement of hormone titers in biological samples, obtained as a result of non-stressful procedures, will lead to a clearer understanding of the effects seen in isolation versus grouping studies. Organ weight studies often appear to be very misleading, particularly in female rodents. It is also hoped that other studies will concern themselves with effects of isolation with respect to other social cues in rodents including odors and ultrasound.     

Effects of husbandry and management systems on physiology and behaviour of farmed and laboratory rabbits

The major issues regarding the welfare of both farmed and laboratory rabbits are reviewed, according to husbandry and management systems. The main stressors that can affect welfare and homeostatic responses in rabbits are also reviewed. An overview of the most widespread housing systems for both farmed and laboratory rabbits is presented. The main problems related to housing and management are identified, in particular those related to individual and group housing, space requirements and group size, as well as human-animal interaction. The effects of psychological and physical stressors on physiology and behaviour are illustrated through examples in various rearing conditions. Psychological stressors include social stress and fear, while physical stressors include environmental variables such as housing system and climatic factors, i.e. heat. Welfare indicators are identified that can be monitored to determine the effects of individual and environmental variables on the animals' possible coping strategies. Physiological indicators include the neuro-endocrine and psycho-neuro-immuno-endocrine measurements, while behavioural indicators include the behavioural repertoire and responses to behavioural tests. Some possible ways to enhance welfare are indicated, such as enrichment of the environment and improved handling procedures.     

The effects of enriching laboratory cages using various physical structures on multiple measures of welfare in singly-housed rats

The single housing of laboratory rats may be recommended in some situations such as hypothesis-driven or test-specific studies, during electroencephalogram recording of phases of sleep and after surgical procedures. However, as single housing of laboratory rats has been shown to be stressful, modification of the housing environment is needed to improve the welfare of these animals. This experiment was carried out to investigate the long-term effects of environmental enrichment on some behavioural, physiological, pathological and psychological measures of welfare. With two batches of animals, 24 rats were housed singly in either enriched cages (EC) (n = 12 cages) or unenriched cages (UC) (n = 12 cages). Behaviour was sampled every week and so was body weight and weight gain over a six-week observation period. Behaviours of the rats in the elevated plus-maze were recorded on the seventh week, whereas organ weights were recorded postmortem. The results revealed that long-term single housing of rats in super-enriched cages increased levels of indicators of good welfare including sleep, exploration, movement and feeding behaviour, body weights, weight gains and the relative weights of the thymus gland and spleen, and decreased levels of indicators of poor welfare such as stationary behaviour and the relative weight of adrenal glands. Thus, enrichment of conventional cages of newly weaned singly-housed laboratory rats with multiple physical structures appeared to improve their ability to control the environment and to promote their species-specific behaviour; changes that can ultimately result in good welfare.     

Behavioral assessment of intermittent wheel running and individual housing in mice in the laboratory

Physical cage enrichment—exercise devices for rodents in the laboratory—often includes running wheels. This study compared responses of mice in enriched physical and social conditions and in standard social conditions to wheel running, individual housing, and open-field test. The study divided into 6 groups, 48 female BALB/c mice group housed in enriched and standard conditions. On alternate days, the study exposed 2 groups to individual running wheel cages. It intermittently separated from their cage mates and housed individually 2 groups with no running wheels; 2 control groups remained in enriched or standard condition cages. There were no significant differences between enriched and standard group housed mice in alternate days' wheel running. Over time, enriched, group housed mice ran less. Both groups responded similarly to individual housing. In open-field test, mice exposed to individual housing without running wheel moved more and faster than wheel running and home cage control mice. They have lower body weights than group housed and wheel running mice. Intermittent withdrawal of individual housing affects the animals more than other commodities. Wheel running normalizes some effects of intermittent separation from the enriched, social home cage.     

Training Nonhuman Primates Using Positive Reinforcement Techniques

Physical cage enrichment—exercise devices for rodents in the laboratory—often includes running wheels. This study compared responses of mice in enriched physical and social conditions and in standard social conditions to wheel running, individual housing, and open-field test. The study divided into 6 groups, 48 female BALB/c mice group housed in enriched and standard conditions. On alternate days, the study exposed 2 groups to individual running wheel cages. It intermittently separated from their cage mates and housed individually 2 groups with no running wheels; 2 control groups remained in enriched or standard condition cages. There were no significant differences between enriched and standard group housed mice in alternate days' wheel running. Over time, enriched, group housed mice ran less. Both groups responded similarly to individual housing. In open-field test, mice exposed to individual housing without running wheel moved more and faster than wheel running and home cage control mice. They have lower body weights than group housed and wheel running mice. Intermittent withdrawal of individual housing affects the animals more than other commodities. Wheel running normalizes some effects of intermittent separation from the enriched, social home cage.     

Animal Welfare Beyond the Cage … and Beyond the Evidence?

In “Laboratory Rodent Welfare: Thinking Outside the Cage,” Balcombe (2010/this issue) suggests that laboratory cage housing is damaging to rats and mice because it does not meet their evolved needs and may damage their psychological and physical health. The article also indicates that larger and more enriched spaces reduce aggression and mortality and improve the health and friendliness of rodents in the laboratory. Remarkably, many of the studies cited as supporting these assertions fail to provide data bearing on the issues involved or may even report findings opposite to those described by Balcombe, whereas many studies that are highly relevant to these issues are not cited or described. Moreover, although the “evolved needs” of rats and mice are presented as the basis for an analysis of rodent welfare, the important and well-documented changes in needs- or motivation-related behaviors of a rodent in the laboratory (due to human selection over hundreds of generations) is ignored. This pattern of disconnections between data and conclusions is so pervasive as to demolish the scientific value of the exposition.     

Impact of 'living apart together' on postoperative recovery of mice compared with social and individual housing

Social housing is the optimal way of housing female laboratory mice. However, individual housing may be required in experimental designs, for example after surgery. We therefore investigated whether housing two female mice in a cage, separated by a grid partition ('living apart together', LAT), counters the adverse effects of individual housing on postoperative recovery. Ten individually housed (IND) mice, nine socially housed (SOC) mice and nine mice, housed LAT, were surgically implanted with a telemetry transmitter. From one week prior to surgery until three weeks thereafter, several physiological and behavioural parameters were measured in the mice subjected to surgery. The telemetry transmitter measured heart rate (HR), body temperature and activity continuously. Body weight, food and water intake were scored regularly, as were wound healing, ease of handling, nest building and behaviour. Results indicated that SOC mice appear to be less affected by abdominal surgery than IND mice, as indicated by HR and behaviour. LAT, however, did not appear to be beneficiary to the mice. Increased HR levels and differences in behaviour as compared with both SOC and IND animals indicate that LAT may even be the most stressful of the three housing conditions. We therefore conclude that mice benefit most from social housing after surgery. If, however, social housing is not possible, individual housing appears to be a better option than separating mice by a grid partition.     

Novel modulators for body weight changes induced by fasting and re-feeding in mice

Catch-up weight gain after malnutrition is a risk factor for metabolic syndrome. Here we show that social isolation enhanced fasting-induced weight loss and suppressed weight gain induced by re-feeding for 6 days following a 24-h fast in prepubertal wild-type mice. These effects of social isolation on weight gain were not associated with significant changes in daily average food consumption. Under the same housing condition, genetic deletion of β-endorphin reduced the fasting-induced weight loss and enhanced the re-feeding-induced weight gain in prepubertal mice. These effects of social isolation or genetic deletion of β-endorphin on these weight changes were attenuated and reversed in postpubertal mice. Moreover, genetic deletion of β-endorphin attenuated these effects of social isolation on the catch-up weight gain in prepubertal mice and reversed them in postpubertal mice. Thus, social isolation, endogenous β-endorphin, and age can be novel modulators for body weight changes induced by fasting and re-feeding in mice.     

Olfaction and olfactory-mediated behaviour in psychiatric disease models

Rats and mice are the most widely used species for modelling psychiatric disease. Assessment of these rodent models typically involves the analysis of aberrant behaviour with behavioural interactions often being manipulated to generate the model. Rodents rely heavily on their excellent sense of smell and almost all their social interactions have a strong olfactory component. Therefore, experimental paradigms that exploit these olfactory-mediated behaviours are among the most robust available and are highly prevalent in psychiatric disease research. These include tests of aggression and maternal instinct, foraging, olfactory memory and habituation and the establishment of social hierarchies. An appreciation of the way that rodents regulate these behaviours in an ethological context can assist experimenters to generate better data from their models and to avoid common pitfalls. We describe some of the more commonly used behavioural paradigms from a rodent olfactory perspective and discuss their application in existing models of psychiatric disease. We introduce the four olfactory subsystems that integrate to mediate the behavioural responses and the types of sensory cue that promote them and discuss their control and practical implementation to improve experimental outcomes. In addition, because smell is critical for normal behaviour in rodents and yet olfactory dysfunction is often associated with neuropsychiatric disease, we introduce some tests for olfactory function that can be applied to rodent models of psychiatric disorders as part of behavioural analysis.     

Social housing influences the composition of volatile compounds in the preputial glands of male rats

In rodents the preputial glands are one of the major sources of pheromones. These volatile chemosignaling compounds are known to elicit specific behavioral and physiological effects in their conspecifics. While social stress can alter both the behavior and hormonal status of rodents, little is known about its influence on the volatile constituents of the preputial glands. We have examined the composition of volatile compounds in the preputial glands of gonadally intact male rats housed for 70 days in either unisex triads (three/cage) or singly. The rank status of triad-housed rats was based on quantitative behavioral assessments taken during the initial 30 min of triad housing. Dominant rats had heavier preputial glands compared to subdominant and subordinate rats. Capillary gas chromatography-mass spectrometry identified 56 volatile preputial compounds, of these 17 did not differ between groups while 26 compounds were significantly higher in the single-housed compared to the triad-housed rats. Six additional volatile compounds were higher in the dominant compared to the other 3 groups, while another six compounds were higher in both the dominant and single-housed rats compared to the subdominant and subordinate rats. It can be concluded that both housing condition and social rank status have significant but different effects on the composition of volatile compounds found in preputial glands of male rats. The physiological and behavioral significance of these changes in preputial gland volatile compound composition in rats remain to be investigated.     

Chronic Subordinate Colony Housing (CSC) as a Model of Chronic Psychosocial Stress in Male Rats

Chronic subordinate colony housing (CSC) is an adequate and reliable mouse model of chronic psychosocial stress, resulting in reduced body weight gain, reduced thymus and increased adrenal weight, long-lasting anxiety-like behaviour, and spontaneous colitis. Furthermore, CSC mice show increased corticotrophin (ACTH) responsiveness to acute heterotypic stressors, suggesting a general mechanism which allows a chronically-stressed organism to adequately respond to a novel threat. Therefore, the aim of the present study was to extend the CSC model to another rodent species, namely male Wistar rats, and to characterize relevant physiological, immunological, and behavioural consequences; placing particular emphasis on changes in hypothalamo-pituitary-adrenal (HPA) axis responsiveness to an acute heterotypic stressor. In line with previous mouse data, exposure of Wistar rats to 19 days of CSC resulted in a decrease in body weight gain and absolute thymus mass, mild colonic barrier defects and intestinal immune activation. Moreover, no changes in stress-coping behaviour or social preference were seen; again in agreement with the mouse paradigm. Most importantly, CSC rats showed an increased plasma corticosterone response to an acute heterotypic stressor (open arm, 5 min) despite displaying similar basal levels and similar basal and stressor-induced plasma ACTH levels. In contrast to CSC mice, anxiety-related behaviour and absolute, as well as relative adrenal weights remained unchanged in CSC rats. In summary, the CSC paradigm could be established as an adequate model of chronic psychosocial stress in male rats. Our data further support the initial hypothesis that adrenal hyper-responsiveness to ACTH during acute heterotypic stressors represents a general adaptation, which enables a chronically-stressed organism to adequately respond to novel challenges.     

Preference for social contact versus environmental enrichment in male laboratory mice

Due to their aggressive nature, male mice are less frequently used than female mice in biomedical research. When aggressive males are being used, individual housing is common practice. The question arises whether this is an acceptable housing for a social species. The present study was designed to gain more insight into the nature of inter-male social contact and into the potential of a form of environmental enrichment (nesting material) to compensate for the lack of social contact. In a series of tests, we analysed whether male mice of different ages preferred to spend time (1) near a familiar cage mate versus an empty cage, or (2) near to a familiar cage mate versus direct contact with nesting material (tissues). Dwelling time in each of the test cages and sleeping sites was recorded, as was the behaviour of the test mice. Results indicated that when other conditions were similar, male mice preferred to sleep in close proximity to their familiar cage mate. Furthermore, the need to engage in active social behaviour increased with age. Tissues were used to a large extent for sleeping and sleep-related behaviour. It is concluded that single housing in order to avoid aggression between male mice is a solution with evident negative consequences for the animals. When individual housing is inevitable due to excessive aggressive behaviour, the presence of nesting material could partly compensate for the deprivation of social contact.     

Report of the 2006 RSPCA/UFAW Rodent Welfare Group meeting

The RSPCA/UFAW Rodent Welfare Group holds a one-day meeting every autumn to discuss current welfare research and to exchange views on rodent welfare issues. A key aim of the group is to encourage people to think about the lifetime experience of laboratory rodents, ensuring that every potential influence on their well-being has been reviewed and refined. Speakers at the 2006 meeting presented preliminary findings of ongoing studies and discussed regulatory updates. Topics included the housing and husbandry of mice and rats, refining the use of rodents in asthma research, good practice for the euthanasia of rodents using carbon dioxide and achieving reduction by sharing genetically modified mice.     

An investigation of playful behaviour in Rattus norvegicus and Mus musculus (Mammalia)

The playful behaviour of laboratory rats ( Rattus norvegicus ) was investigated in litters of five individuals with the mother present; parallel observations were made on mice ( Mus musculus ). Seven mixed litters containing four young rats and a young mouse fostered at birth were also observed.
Solitary play was recorded in both species and took a similar form but social play was only observed in rats. In rats, solitary play frequently preceeded social play.
The behavioural elements involved in the social play of Rattus norvegicus were described, and the majority of these were the playful equivalent of adult agonistic behaviour elements. These social play elements were found to be organized into definite sequences which differed from those of adult aggression. Each behavioural element was found to act as a social releaser.
Young mice did not respond playfully to social play from a rat litter mate; mice were less attractive to rats as playmates in comparison with fellow rats.     

Social interaction in nonhuman primates: an underlying theme for primate research.

Social living is assumed to be a critical feature of nonhuman primate existence inasmuch as most primate species live in social groups in nature. Recent USDA legislation emphasizes the importance of social contact in promoting psychological well-being and recommends that laboratory primates be housed with companions when consistent with research protocols. Our goals were to examine the link between social housing and psychological well-being and to explore the idea that research may be compromised when primates are studied in environments that vary too greatly from their natural ecological setting (individual cage housing versus group housing). Three general points emerge from these examinations. First, providing companionship may be a very potent way in which to promote psychological well-being in nonhuman primates; however, social living is not synonymous with well-being. The extent to which social housing promotes psychological well-being can vary across species and among individual members of the same species (for example, high- and low-ranking monkeys). Secondly, housing conditions can affect research outcomes in that group-housed animals may differ from individually housed animals in response to some manipulation. Social interaction may be a significant variable in regulating the biobehavioral responses of nonhuman primates to experimental manipulations. Finally, a larger number of socially housed subjects than individually housed subjects may be necessary for some biomedical research projects to yield adequate data analysis. Thus, social living has significant benefits and some potential costs not only for the animals themselves, but for the research enterprise.     

Effects of housing conditions on the development of wet skin lesions in the NOA mouse.

The effects of housing on the onset time and prevalence of wet skin lesions were investigated in NOA mice, which spontaneously develop these lesions at a high rate. Wet skin lesions developed earliest in mice that were housed individually. For mice that were housed in groups, the lesions developed earlier in mice with non-littermate group housing than in mice with littermate group housing. The prevalence of lesions was in the following order: individual housing > non-littermate group housing > littermate group housing. These results suggest that socio-psychological factors are involved in the etiology of wet skin lesions in the NOA mouse. Under individual housing conditions, two other novel characters of the NOA mouse were also observed, specifically, development of dry skin and wet skin lesions at the tail root. These characteristics developed early and with high prevalence and were easily observed on external examination. Therefore, these novel characteristics observed in NOA mice are potential markers of the psychological state of the animals.     

The Lonely Mouse – Single Housing Affects Serotonergic Signaling Integrity Measured by 8-OH-DPAT-Induced Hypothermia in Male Mice

Male BALB/c mice single-housed for a period of three weeks were found to respond with a more marked hypothermia to a challenge with a selective serotonergic agonist (8-OH-DPAT) than their group-housed counterparts. This effect of single housing was verified by screening a genetically heterogeneous population of male mice on a C57BL/6 background from a breeding colony. Enhanced activity of the implicated receptor (5-HT_1A) leading to an amplified hypothermic effect is strongly associated with depressive states. We therefore suggest that the 8-OH-DPAT challenge can be used to demonstrate a negative emotional state brought on by e.g. long-term single housing in male laboratory mice. The study emphasizes the importance of social housing, and demonstrates that male mice deprived of social contact respond with altered serotonergic signaling activity. Male mice not only choose social contact when given the option, as has previously been shown, but will also, when it is deprived, be negatively affected by its absence. We propose that the 8-OH-DPAT challenge constitutes a simple, but powerful, tool capable of manifesting the effect of social deprivation in laboratory mice. It potentially allows not only for an unbiased, biochemical evaluation of psychological stressors, but may also allow for determining whether the effect of these can be counteracted.     

Environmental enrichment for laboratory rodents: animal welfare and the methods of science

Because of the difficulty of' establishing objective measures of laboratory rodents' psychological well-being, developing environmental enrichment programs that are actually beneficial to rodents destined to participate in laboratory research is particularly challenging. Many studies of effects of environmental complexity, social housing, and increases in cage size suggest that professional judgments as to the impact of diverse types of environmental enrichment on rodent welfare are not a reliable basis for evaluating the outcomes of enrichment programs for laboratory rodents. Successful enrichment programs will vary from one rodent species to another, between sexes, as well as between age classes. There is a need for objective, measurable goals for proposed environmental enrichment programs for rodents, as well a s for empirical investigations of the beneficial and detrimental consequences of proposed environmental manipulations.     

Risk factors for Toxoplasma gondii infection in wild rodents from central coastal California and a review of T. gondii prevalence in rodents

Sera from 523 wild rodents were tested for Toxoplasma gondii antibodies using either an indirect fluorescent antibody test (IFAT) (rats and mice, with titer >or=80 considered positive) or a latex agglutination test (LAT) (voles, squirrels, and pocket mice, with titer >or=32 considered positive). Seventeen percent (88/523) of the rodents, including 26% (85/328) of the Peromyscus sp. and 8% (3/37) of Spermophilus beecheyi, were seropositive. Fourteen percent (23/161) of rodents captured in trap sites next to Morro Bay (California) and 15% (16/109) of rodents from sites adjacent to riparian habitats had antibodies to T. gondii, compared to 19% (49/253) of rodents captured in habitats not associated with water; this difference was not statistically significant (P = 0.32). Significantly fewer rodents were captured <200 m from residential housing compared to locations further away (11% vs. 30%, respectively). Factors associated with an increased risk for T. gondii seropositivity in rodents were capture location >or=200 m from residential housing and adult age.     

Environmental Enrichment for Laboratory Rodents: Animal Welfare and the Methods of Science

Because of the difficulty of' establishing objective measures of laboratory rodents' psychological well-being, developing environmental enrichment programs that are actually beneficial to rodents destined to participate in laboratory research is particularly challenging. Many studies of effects of environmental complexity, social housing, and increases in cage size suggest that professional judgments as to the impact of diverse types of environmental enrichment on rodent welfare are not a reliable basis for evaluating the outcomes of enrichment programs for laboratory rodents. Successful enrichment programs will vary from one rodent species to another, between sexes, as well as between age classes. There is a need for objective, measurable goals for proposed environmental enrichment programs for rodents, as well a s for empirical investigations of the beneficial and detrimental consequences of proposed environmental manipulations.