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Query: UNIPROT:Q86TM3 (cage)
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The effect of housing density of mice on the thermogenic state and capacity of their brown adipose tissue was studied. Mice were housed one, two, or six per cage at 28 degrees C for 15 days. Increased housing density suppressed the thermogenic capacity of brown adipose tissue (decreased the total amount of uncoupling protein) and decreased the thermogenic state of brown adipose tissue mitochondria (decreased GDP binding). A density of six mice per cage had a greater effect than a density of two mice per cage. The size of brown adipose tissue (wet weight and protein content), the content of mitochondria in it (cytochrome oxidase content), and the total activity of thyroxine 5'-deiodinase were not altered by housing density. We conclude that even at a temperature close to thermoneutrality (29-33 degrees C for the mouse), the occurrence of social thermoregulation (huddling) reduces the requirement for brown adipose tissue thermogenesis and results in a reduction in its thermogenic capacity. It is clearly of importance that the design of studies of mouse brown adipose tissue take into account not only the temperature at which the mice are housed, but also the number of mice housed per cage.
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PMID:Number of mice per cage influences uncoupling protein content of brown adipose tissue. 132 3

Reduced clonidine anti-nociception in mice given low doses of dexamethasone has encouraged us to investigate the effects of dexamethasone pretreatment on locomotor hypoactivity, another example of clonidine-induced behaviour in mice. Dexamethasone administered intraperitoneally (0.1, 1.0, 10 mg kg-1) 30 min before clonidine reduced clonidine-induced locomotor hypoactivity in the activity cage to an extent which was dose-dependent. Dexamethasone administered centrally (10 ng/mouse) 30 min before clonidine was also able to reduce clonidine-induced locomotor hypoactivity. Cycloheximide administered at a dose of 10 mg kg-1 2 h before clonidine did not change the effects of clonidine but was able to prevent the effects of dexamethasone on clonidine-induced hypoactivity. The glucocorticoid receptor antagonist RU38486 administered centrally at the dose of 1 ng/mouse did not change the effects of clonidine, whereas it was able to block the effects of dexamethasone on clonidine-induced locomotor hypoactivity. These results suggest that the effects of dexamethasone on clonidine-induced locomotor hypoactivity depend on the stimulating effects that dexamethasone exerts on the protein synthesis via the glucocorticoid receptor in the brain.
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PMID:Dexamethasone reduced clonidine-induced hypoactivity in mice. 883 96

Peripheral administration of interleukin-1beta (IL-1beta) in rodents reduces exploratory behavior in a novel environment while decreasing social investigation of a juvenile conspecific. In this study we wanted to test the effects of peripherally administered IL-1beta on another aspect of the mouse social repertoire, namely intraspecific fighting towards an adult male intruder. In the first experiment, sickness behavior induced by IL-1beta (1 microg/mouse) in adult CD-1 mice was assessed by direct observation of behavioral changes following placement into a novel environment. Three hours after injection, subjects were individually introduced for 20 min in a cage with clean sawdust and a number of behavioral items recorded. Blood samples were collected at the end of the testing session. Body temperature was measured right before, 1 h and 3.5 h following injection. In IL-1beta treated mice, exploration (assessed by measuring duration and frequency of Wall Rearing and Rearing behaviors) was nearly totally suppressed, while duration and frequency of behaviors such as Grooming, Bar Holding, and Digging were also markedly reduced. Administration of IL-1beta significantly elevated CORT secretion above basal levels and, as previously reported for mice, induced hypothermia (about 2 degrees C). In the second experiment, we assessed mice receiving IL-1beta (0.25; 0.5 or 1 microg/mouse or saline solution) in a social context. Three hours after injection, subjects were placed into a neutral cage for 20 min with a non-injected adult male conspecific and aggressive behavior scored. Overall, IL-1beta administration affected the social repertoire of treated mice in a dose-dependent fashion. Specifically, agonistic components of aggressive behavior were nearly totally suppressed, while the defensive elements, such as Upright Defensive posture, Upright Submissive posture, Crouching, or Flee were not affected by IL-1beta. Overall these data support the notion that sickness behavior induced by IL-1beta administration represents an organized behavioral strategy and is not an aspecific response to an illness-type of condition.
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PMID:Behavioral effects of peripheral interleukin-1 administration in adult CD-1 mice: specific inhibition of the offensive components of intermale agonistic behavior. 959 59

The effects of dexamethasone pretreatment on clonidine-induced antinociception and locomotor hypoactivity were investigated in mice. In the hot-plate and the tail-flick tests, dexamethasone administered intraperitoneally at a dose of 1 mg kg(-1), 30 or 60 min before clonidine, reduced clonidine antinociception in both tests and reduced clonidine-induced locomotor hypoactivity in the activity cage. When administered 15 min before clonidine, dexamethasone had no effect on clonidine antinociception. A higher dexamethasone dose (10 mg kg(-1)) induced the same effects observed at a dose of 1 mg kg(-1) in the hot-plate and the tail-flick tests, but the former dose had a stronger effect on locomotor hypoactivity. Dexamethasone (10 ng/mouse) administered intracerebroventricularly 30 min before clonidine was also able to reduce both clonidine-induced antinociception and locomotor hypoactivity. The protein synthesis inhibitor, cycloheximide, administered intraperitoneally at the dose of 10 mg kg(-1), 2 h before clonidine, was able to prevent dexamethasone effects on clonidine-induced antinociception. The glucocorticoid receptor antagonist RU-38486, administered intracerebroventricularly at the dose of 1 ng/mouse, was also able to block dexamethasone effects on clonidine-induced antinociception and locomotor hypoactivity, whereas both cycloheximide and RU-38486 per se did not influence pain sensitivity or locomotor activity. These results suggest that the dexamethasone effects on clonidine-induced antinociception and locomotor hypoactivity depend on the stimulating effects that dexamethasone exert, on the protein synthesis via the glucocorticoid receptor in the brain.
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PMID:Clonidine-induced antinociception and locomotor hypoactivity are reduced by dexamethasone in mice. 1129 50

Interleukin (IL)-2 is a cytokine that influences exploratory behavior and central dopamine activity in rodents, and induces schizophrenic-like behavior and cognitive deficits in humans. We presently report that a single i.p. injection of murine IL-2 (0.05-0.80 microg/mouse) induced significant increases in novelty-induced locomotion and exploration in BALB/c mice. These measures were not significantly altered in mice that were pre-exposed to the test cage prior to cytokine injection. The IL-2-induced behavioral changes were not further augmented by repeated intermittent injections (five daily i.p. injections; 0.4 microg/mouse), however. Nonetheless, during the treatment period, activity scores of IL-2-treated mice significantly exceeded those of mice receiving saline; hence, repeated injections of IL-2 induced a persistent behavioral activation. IL-2 treatment also increased sensitivity to the behavior-stimulating effects of GBR 12909, a highly selective dopamine uptake inhibitor. This effect was a very long-lasting one since the dopamine agonist was administered 6 weeks after cessation of IL-2 treatment. The latter finding indicates that IL-2 interacts with the mesolimbic dopamine system, changing its sensitivity to seemingly different substances. Based on these data, and those of Zalcman and colleagues (S. Zalcman, I. Savina, R.A. Wise, Interleukin-6 increases sensitivity to the locomotor-stimulating effects of amphetamine in rats, Brain Res. 847 (1999) 276-283), it is suggested that cytokines can influence the development of behavioral abnormalities that are characteristic of aberrant mesolimbic dopamine activity via sensitization-like processes.
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PMID:Interleukin-2 potentiates novelty- and GBR 12909-induced exploratory activity. 1131 62

Studies were initiated to determine the effects of restricted (32.2 cm2 per mouse), normal (96.8 cm2), or excess floor space (129.0 cm2) allowances by using a model of three mice per cage. BALB/cJ mice were bred on-site and weaned at 3 weeks of age into specially designed polycarbonate shoebox cages modified to each space allowance. Cages contained aspen shavings for bedding, and mice were fed and watered ad libitum. Body weight gains, feed and water use, and immunologic measures largely were not effected by floor space allowances. Female BALB/cJ mice were heavier and had increased lymphocyte blastogenesis to phytohemagglutinin (20 microg/mL) when given 32.2 cm2/mouse than when given 129 cm2/mouse. Female mice showed an increase in grooming and sitting behaviors when given 32.2 cm2/mouse, but male mice with restricted floor space spent more time lying down but showed no change in grooming or sitting behaviors compared to mice given more space. Among male mice, limited floor space did not significantly influence growth rates, but male mice given 32.2 cm2/mouse had less mortality than did mice given more space. We conclude that floor spaces as limited as 32.2 cm2/mouse did not cause behavior, health, immune or performance problems for BALB/cJ mice.
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PMID:Floor space needs for laboratory mice: BALB/cJ males or females in solid-bottom cages with bedding. 1135 20

Measures of performance, mortality, adrenal weights, plasma glucocorticoid concentration, and selected immune measures were collected in an attempt to define space needs of laboratory mice. Six replications of 3 C57BL/6 male mice per cage were examined while housed on bedding at 5, 10, 15, or 20 in(2) (32.2, 64.5, 96.8, or 129 cm(2)) per mouse. Body weights were not influenced by treatment; however, mice in smaller spaces (5 in(2) per mouse) consumed or wasted more feed and water than mice given greater space allowances. Mice given the least amount of space (5 in(2) per mouse) had greater lymphocyte proliferation in response to the T-cell mitogen PHA than mice given more space. Mice provided 10 in(2) per mouse had greater natural killer cytotoxicity than mice given greater or less space. Mouse mortality was greater as more space was provided. In contrast, adrenal weights and plasma glucocorticoid concentrations were progressively greater with lower space allowances. The National Research Council 1996 recommendation of 15 in(2) per mouse, for this strain and sex of mice, would result in greater mortality and reduced activity of some immune measures. Socially housed male C57BL/6 mice will benefit from less space than recommended by the National Research Council in 1996.
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PMID:Floor Space Needs for Laboratory Mice: C56BL/6 Males in Solid-bottom Cages with Bedding. 1140 86

The present studies compared the effect of parenteral administration of the proinflammatory cytokine interleukin-1beta (IL-1beta) on food-seeking behavior under various conditions. IL-1beta (100 ng/mouse) decreased home cage consumption of sweetened milk to a greater extent in ad libitum fed mice than in mice that were food-restricted to maintain 85-90% of their free-feeding body weight. When operant responding for milk was maintained under a fixed-ratio 10 response (FR10) schedule of milk delivery, IL-1beta (30-300 ng/mouse) significantly decreased milk-maintained responding in mice fed ad libitum, but not in food-restricted mice. When food-restricted mice were trained under either an FR4 or FR32 response schedule of milk delivery, IL-1beta (100-300 ng/mouse) produced significant decreases in FR32, but not in FR4 responding. When responding was maintained under a progressive-ratio 10 response (PR10) schedule of milk delivery, IL-1beta (30-300 ng/mouse) dose-dependently decreased breaking points. These results indicate that the effects of IL-1beta on food-maintained behavior depend on both the level of motivation (as assessed by food restriction) and on the response cost for the milk (as assessed by ratio requirement). These findings suggest that motivational factors may be capable of attenuating some of the behavioral effects of these agents.
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PMID:Effects of interleukin-1beta on food-maintained behavior in the mouse. 1209 86

The Guide for the Care and Use of Laboratory Animals (the Guide) is widely accepted as the housing standard by most Institutional Animal Care and Use Committees. The recommendations are based on best professional judgment rather than experimental data. Current efforts are directed toward replacing these guidelines with data-driven, species-appropriate standards. Our studies were undertaken to determine the optimum housing density for C57BL/6J mice, the most commonly used inbred mouse strain. Four-week-old mice were housed for 8 weeks at four densities (the recommended approximately 12 in2 [ca. 77.4 cm2]/mouse down to 5.6 in2 [ca. 36.1 cm2]/mouse) in three cage types with various amounts of floor space. Housing density did not affect a variety of physiologic parameters but did affect certain micro-environmental parameters, although these remained within accepted ranges. A second study was undertaken housing C57BL/6J mice with as little as 3.2 in2/mouse (ca. 20.6 cm2). The major effect was elevated ammonia concentrations that exceeded limits acceptable in the workplace at increased housing densities; however, the nasal passages and eyeballs of the mice remained microscopically normal. On the basis of these results, we conclude that C57BL/6J mice as large as 29 g may be housed with 5.6 in2 of floor space per mouse. This area is approximately half the floor space recommended in the Guide. The role of the Guide is to ensure that laboratory animals are well treated and housed in a species-appropriate manner. Our data suggest that current policies could be altered in order to provide the optimal habitation conditions matched to this species' social needs.
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PMID:Effects of housing density and cage floor space on C57BL/6J mice. 1567 64

Some recommendations in the Guide for the Care and Use of Laboratory Animals (the Guide) are based on best professional judgment. Our current efforts are directed toward replacement with data-driven standards. We demonstrated earlier that young adult C57BL/6J mice could be housed with half the floor space recommended in the Guide without discernable negative effects. This report extends that work by examining optimal housing densities for young adult male and female BALB/cJ, NOD/LtJ, and FVB/NJ mice. These 8-week studies were initiated with 3-week-old BALB/cJ and NOD/LtJ mice and 3- to 5-week-old FVB/NJ mice housed in three cage types. We adjusted the number of mice per cage to house them with the floor space recommended in the Guide (approximately 12 in2 [ca. 77 cm2] per mouse) down to 5.6 in2 [ca. 36 cm2] per mouse. Early-onset aggression occurred among FVB/NJ male mice housed at all densities in cages having 51.7 in2 (ca. 333 cm2) or 112.9 in2 (ca. 728 cm2) of space. FVB/NJ male mice housed in shoebox (67.6 in2 [ca. 436 cm2]) cages did not exhibit aggression until the fifth week. Urinary testosterone output was density-dependent only for BALB/cJ male mice in shoebox cages (output decreased with increasing density) and FVB/NJ male mice. We conclude that all but FVB/NJ male mice can be housed with half the floor space specified in the Guide. The aggression noted for male FVB/NJ mice may have been due to their age span, although this did not impact negatively on the female FVB/NJ mice.
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PMID:Effects of housing density and cage floor space on three strains of young adult inbred mice. 1615 12


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