Individually-housed Mice Research Articles

Social Housing Leads to Increased Ethanol Intake in Male Mice Housed in Environmentally Enriched Cages.

An individual's social environment affects alcohol intake. However, the complex interactions between social context and alcohol intake remain understudied in preclinical models. In the present study, we sought to characterize the effects of social housing on voluntary ethanol intake in male C567BL/6J mice using a continuous access two-bottle choice model. This was accomplished using HM2 cages, which allow for the continuous monitoring of individuals' fluid intake through radiofrequency tracking while they remain undisturbed in a group setting. These cages are moderately environmentally enriched compared to standard shoebox cages. By analyzing the levels of voluntary ethanol intake between socially- and individually-housed mice in HM2 cages, we were able to parse apart the effects of environmental enrichment vs. social enrichment. We found that while intake levels were overall lower than those observed when animals are singly housed in standard shoebox cages, socially-housed males consumed significantly more ethanol compared to individually-housed mice, suggesting that while environmental enrichment attenuates ethanol intake, social enrichment may, in fact, potentiate it. This effect was not specific for alcohol, however, in that ethanol preference did not differ as a product of social context. We also found that the total number of non-consummatory channel entries were consistently higher in individually-housed mice. Additionally, a single corticotropin releasing factor receptor 1 antagonist treatment significantly decreased both water and ethanol intake in socially- and individually-housed mice up to 3 h post-treatment, though the effect on water intake was longer lasting. This treatment also significantly decreased the number of non-consummatory channel entries in individually-housed mice, but not in socially-housed mice, suggesting that increased channel visits may be a stress-related behavior. Lastly, we examined blood ethanol concentrations and FosB immunoreactivity to characterize the physiological responses to ethanol intake in socially- and individually-housed mice. The number of FosB-positive cells in the centrally-projecting Edinger-Westphal nucleus and nucleus accumbens shell positively correlated with average baseline ethanol intake in individually-housed mice, but not in socially-housed mice. Overall, we found that social, but not environmental, enrichment can increase ethanol intake in male C57BL/6J mice. Future studies need to test this phenomenon in female mice and assess the generalizability of this finding.

Making "Good" Choices: Social Isolation in Mice Exacerbates the Effects of Chronic Stress on Decision Making.

Chronic stress can impact decision-making and lead to a preference for immediate rewards rather than long-term payoffs. Factors that may influence these effects of chronic stress on decision-making are under-explored. Here we used a mouse model to investigate the changes in decision-making caused by the experience of chronic stress and the role of social isolation in exaggerating these changes. To test decision-making, mice were trained to perform a Cost-Benefit Conflict (CBC) task on a T-maze, in which they could choose between a high-reward, high-risk alternative and a low-reward, low-risk alternative. Mice were either housed in groups or alone throughout the experiment. Both groups of mice underwent a seven-day period of repeated immobilization to induce chronic stress. Stress levels were confirmed using behavioral (open field test) and physiological (urine corticosterone ELISA) measures. We found a significant increase in frequency of high-risk decisions after exposure to chronic stress among both socially- and individually-housed mice. Crucially, socially-housed mice showed a significantly smaller increase in high-risk decision-making compared to singly-housed mice. These findings suggest that chronic stress leads to an increase in high-risk decision-making in mice, and that lack of social interaction may exacerbate this stress effect.

Greater lowering of brain and adrenal catecholamines in group-housed than in individually-housed mice administered DL-alpha-methyltyrosine.

Greater lowering of brain and adrenal catecholamines in group-housed than in individually-housed mice administered DL-alpha-methyltyrosine.

Social Isolation Reduces Mammary Development, Tumor Incidence, and Expression of Epigenetic Regulators in Wild-type and p53-Heterozygotic Mice

Chronic stress is associated with more rapid tumor progression, and recent evidence suggests that stress may contribute to social and ethnic disparities in the incidence and mortality of breast cancer. We evaluated the p53(+/-) FVB/N mouse as a model to investigate effects of chronic social stress on mammary gland development, gene expression, and tumorigenesis. We individually housed (IH) wild-type and p53(+/-) female FVB/N mice, starting at weaning. At 14 weeks of age, both wild-type and p53(+/-) IH mice showed strikingly reduced mammary development compared with group-housed (GH) controls, with IH mice having significantly fewer preterminal end buds. This morphologic difference was not reflected in levels of mammary transcripts for estrogen receptor-alpha or progestin receptor. However, IH increased levels of mRNA for the kisspeptin receptor in the medial preoptic area of the hypothalamus, associated with reduced duration of estrous cycles. Furthermore, IH altered mammary transcripts of genes associated with DNA methylation; transcripts for methyl-binding protein 2 and DNA methyltransferase 3b (DNMT3b), but not DNMT1 and DNMT3a, were reduced in IH compared with GH females. Interestingly, the glands of p53(+/-) females showed reduced expression of all these mediators compared with wild-type females. However, contrary to our initial hypothesis, IH did not increase mammary tumorigenesis. Rather, p53(+/-) GH females developed significantly more mammary tumors than IH mice. Together, these data suggest that social isolation initiated at puberty might confound studies of tumorigenesis by altering mammary development in mouse models.

Individual housing of mice — Impact on behaviour and stress responses

The replicability of results derived from studies in rodents might be influenced by stress caused by inappropriate housing conditions. Here we compared the experimental behaviour and stress response (circulating corticosterone level and adrenal tyrosine hydroxylase activity) of individually-housed male and female inbred mice with that of animals housed in social groups. All mice were behaviourally tested in the modified hole board test (mHB). Male C57BL/6, BALB/c and A mice housed in groups of 3 were compared with individually-housed mice. In a subsequent experiment female C57BL/6 and BALB/c mice were housed under similar conditions. To exclude the possible effects of within-cage order of testing, only one individual per group was behaviourally tested. Neither male nor female mice housed individually showed stronger signs of stress than their socially-housed counterparts. However, we observed a within-cage order effect on the hormonal stress response (corticosterone) in socially-housed female C57BL/6 mice. No effects of individual housing on behaviour in the mHB were found.

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.

D-Cycloserine enhances social behaviour in individually-housed mice in the resident-intruder test

D-Cycloserine (DCS) has been reported to affect the central nervous system in man. To investigate whether the compound produces specific behavioural effects, DCS was administered to male mice in a resident-intruder situation and the behaviour of the interacting mice assessed using ethological analysis. Resident mice given DCS (32.0-320.0 mg/kg PO, 60 min before testing) showed dose-dependent increases in social investigation, smaller increases in sexual behaviour and decreased aggressiveness. Defensive and flight behaviour were not affected. Intruder mice showed slight increases in sexual behaviour that were not dose-dependent, and small increases in social investigation. The increases in social investigation induced by DCS (320.0 mg/kg) in resident mice were not reversible with R-HA 966 (32.0 mg/kg IP, 30 min before testing), a blocker of the strychnine-insensitive glycine modulatory site associated with the N-methyl-D-aspartate receptor, but were blocked by the GABA antagonist bicuculline (0.56 mg/kg IP, 5 min before testing). The small DCS-induced increase in sexual behaviour in residents was reversed by R-HA 966. Within the parameters of the resident-intruder situation, DCS exerts socio-sexual behaviour-enhancing effects which are dependent upon the role of the interactant, and which are mediated by an action upon multiple substrates. DCS may be regarded as another example of a sociotropic (approach-promoting) agent.

Dopamine autoreceptor agonists attenuate spontaneous motor activity but not spontaneous fighting in individually-housed mice

The present study was conducted to determine whether or not two behavioral characteristics of individually-housed mice, hyperactivity in a novel environment and intermale fighting, are attenuated by the dopamine (DA) agonists, apomorphine, (+)- and (-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP). Autoreceptor-activating doses of these drugs which reduced spontaneous activity in a novel environment did not inhibit spontaneous fighting with conspecific olfactory bulbectomized males. Individually-housed mice were more active in a novel environment and showed a significant reduction of activity at lower doses of apomorphine, (+)- and (-)-3-PPP than group-housed mice. However, the ED50's for the inhibition of spontaneous activity in a novel environment in group- and individually-housed mice were similar: apomorphine, 0.02 vs. 0.012 mg/kg, SC; (+)-3-PPP, 0.50 vs. 0.51 mg/kg, SC; and (-)-3-PPP, 1.0 vs. 0.56 mg/kg, SC, for group- and individually-housed mice respectively. A significant proportion of individually-housed mice, but not group-housed mice, displayed catalepsy in response to high doses of (-)-3-PPP. These data suggest that DA autoreceptor agonists can modulate the hyperactivity syndrome but not spontaneous fighting behavior in individually-housed mice.

Alcohol increases both locomotion and immobility in mice: an ethological analysis of spontaneous motor activity.

The effects of alcohol on locomotor activity of group- and individually-housed mice were studied using direct ethological observations, including a detailed postural analysis and measures of both locomotion and immobility. Ethanol (0, 0.5, 1.0 and 2.0 g/kg, IP) was given to subjects placed alone in a novel cage, and videotape recordings of behaviour were made. Locomotor activity was unchanged or increased by alcohol administration. Immobility was profoundly increased, however, at both the intermediate and high doses of alcohol, so that there was a simultaneous increase in measures of both locomotion and immobility. These increases were possible because of a decrease in certain active but non-locomotor elements of behaviour, such as rearing and digging. There generally appeared to be little effect of differential housing, although blood alcohol levels were significantly higher in group-housed animals. This depressant effect of alcohol would probably not be detected by simply recording locomotor activity, since ambulation itself was unchanged or increased. Measurements of both locomotion and immobility may thus more accurately detect stimulant and depressant effects of drugs.

Involvement of various senses in responses to individual housing in laboratory albino mice: 1.The olfactory sense

Abstract ‘Isolation’ of male mice is much used to induce aggressiveness but, as practised in most laboratories, does not preclude communication between neighbouring conspecifics. This study examines the influence of olfaction on individual housing-induced social conflict between male laboratory mice. Attempts were made both to eliminate and to intensify the exposure to presumably socially meaningful odours. First, the effects of acute and chronic anosmia induced by application of four per cent zinc sulphate solution to the nostrils were determined in mice from a range of ages and social experiences. Secondly, the influences on the subsequent aggressiveness of the individually-housed male mice were estimated after introducing into their cages odoriferous bedding from groups of male and of female conspecifics. Both acute and chronic anosmia depressed the attacks directed towards ‘standard opponents’; indeed the chronic treatment virtually abolished this behaviour. Adding odoriferous bedding from the cages o...

Effects of the duration of individual or group housing on behavioural and adrenocortical reactivity in male mice

Male ‘TO’ strain mice were individually or group-housed for different durations (7–196 days). Behavioural reactivity was assessed over 3 days in each category in a novel arena and an emergence test. Plasma samples were later collected after 5 min exposure to ether vapour, these generated stress corticosterone values. Basal corticosterone titres were obtained from similar untested and unanaesthetized categories of mice. Ether stress values were obtained from a limited number of mice subjected to ether anaesthesia but no behavioural testing. The basal adrenocortical activity of these two housing categories did not differ. With longer periods of isolation stress corticosterone values were higher than in comparable grouped animals. Individually-housed mice had significantly lower defaecation scores and exhibited higher levels of exploratory rearing in a novel arena than grouped mice. At about the time an isolated mouse became increasingly aggressive, it became less active in the open-field, and adrenal reactivity increased. Although the relationship is only correlational in nature, it is possible these measures have a common basis.

Comparison of agonistic behavior in individually-housed male mice with those cohabiting with females

Comparison of agonistic behavior in individually-housed male mice with those cohabiting with females

Temporal patterns of voluntary alcohol intake.

This paper describes methods of analysing temporal patterns of alcohol consumption by mice over time-courses of days or hours. Records of daily alcohol intake can be used to identify brief periods when the mice sobered up. These one-day 'breaks' apparently allow the previously acquired level of physical dependence to decay. Effective alcohol intake, calculated by taking account of breaks, is a good indicator of physical dependence. More detailed time studies show the circadian rhythm of intake and of blood alcohol levels. To analyse our records of alcohol consumption over successive 8-hour periods, we fitted the data to cosine curves. These curves show the amplitude of the intake rhythm, which in turn determines the stability of blood alcohol levels. The highest and most stable blood alcohol levels were obtained by administering alcohol in a liquid diet to individually-housed mice.